Propionibacteria

Rev Med Liege, 2004 Nov, 59(11), 626 - 9
{Belgian consensus document on the treatment of acne}; de la Brassinne M et al.; This article describes the consensus on the treatment of acne, reached by a Belgian working group . An effective treatment has to rely as much as possible on the pathophysiologic factors: the increased production of sebum, the abnormal desquamation (retention hyperkeratosis) of the epithelium of he sebaceous gland, the proliferation of Propionibacterium acnes and inflammation . The therapeutic arsenal contains topical as well as systemic drugs . This consensus gives an overview of both modalities and an algorithm is presented describing the practical approach to acne treatment.

J Clin Microbiol, 2005 Jan, 43(1), 326 - 34
Propionibacterium acnes types I and II represent phylogenetically distinct groups; McDowell A et al.; Although two phenotypes of the opportunistic pathogen Propionibacterium acnes (types I and II) have been described, epidemiological investigations of their roles in different infections have not been widely reported . Using immunofluorescence microscopy with monoclonal antibodies (MAbs) QUBPa1 and QUBPa2, specific for types I and II, respectively, we investigated the prevalences of the two types among 132 P . acnes isolates . Analysis of isolates from failed prosthetic hip implants (n = 40) revealed approximately equal numbers of type I and II organisms . Isolates from failed prosthetic hip-associated bone (n = 6) and tissue (n = 38) samples, as well as isolates from acne (n = 22), dental infections (n = 8), and skin removed during surgical incision (n = 18) were predominately of type I . A total of 11 (8%) isolates showed atypical MAb labeling and could not be conclusively identified . Phylogenetic analysis of P . acnes by nucleotide sequencing revealed the 16S rRNA gene to be highly conserved between types I and II . In contrast, sequence analysis of recA and a putative hemolysin gene (tly) revealed significantly greater type-specific polymorphisms that corresponded to phylogenetically distinct cluster groups . All 11 isolates with atypical MAb labeling were identified as type I by sequencing . Within the recA and tly phylogenetic trees, nine of these isolates formed a cluster distinct from other type I organisms, suggesting a further phylogenetic subdivision within type I . Our study therefore demonstrates that the phenotypic differences between P . acnes types I and II reflect deeper differences in their phylogeny . Furthermore, nucleotide sequencing provides an accurate method for identifying the type status of P . acnes isolates.

Lancet, 2004 Dec 18, 364(9452), 2188 - 95
Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial; Ozolins M et al.; BACKGROUND: We investigated the efficacy and cost-effectiveness of five antimicrobial regimens for mild to moderate facial acne and whether propionibacterial antibiotic resistance affects treatment response . METHODS: In this randomised, observer-masked trial, 649 community participants were allocated one of five antibacterial regimens . Primary outcomes were patients' self-assessed improvement and reduction in inflamed lesions at 18 weeks . Analyses were by intention to treat . FINDINGS: Moderate or greater improvement at 18 weeks was reported in 72 (55%) of 131 participants assigned oral oxytetracycline plus topical placebo, 70 (54%) of 130 assigned oral minocycline plus topical placebo, 78 (60%) of 130 assigned topical benzoyl peroxide plus oral placebo, 84 (66%) of 127 assigned topical erythromycin and benzoyl peroxide in a combined formulation plus oral placebo, and 82 (63%) of 131 assigned topical erythromycin and benzoyl peroxide separately plus oral placebo . Most improvement occurred in the first 6 weeks . Treatment differences for the proportion of people with at least moderate improvement were: minocycline versus oxytetracycline -1.2% (unadjusted 95% CI -13.3 to 10.9); combined erythromycin and benzoyl peroxide versus oxytetracycline 11.1% (-0.7 to 22.9) and versus minocycline 12.3% (0.4 to 24.2); erythromycin and benzoyl peroxide separately versus combined formulation -3.5% (-15.2 to 8.2); benzoyl peroxide versus oxytetracycline 5.0% (-7.0 to 17.0), versus minocycline 6.2% (-5.8 to 18.2), and versus combined formulation -6.1% (-17.9 to 5.7) . Benzoyl peroxide was the most cost-effective treatment . Efficacy of both tetracyclines was reduced by pre-existing tetracycline resistance . INTERPRETATION: Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations are similar in efficacy to oral oxytetracycline and minocycline and are not affected by propionibacterial antibiotic resistance.

BMC Nephrol . 2004 Dec 21;5(1):18 {Epub ahead of print}
Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: A case report; Koya D et al.; {Background} The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high . Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined . {Case Presentation} Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis . He had a history of ventricular septum defect (VSD) . A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve . Specimens of blood demonstrated Propionibacterium acnes . The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days . After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved . {Conclusion} Although renal function in our case worsened despite therapy with antibiotics, a short-term and low does of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure . We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully.

Prikl Biokhim Mikrobiol, 2004 Nov-Dec, 40(6), 645 - 8
{Isolation of cobalt-resistant strains of propionic acid bacteria, potent producers of vitamin B12}; In vitro activities of cefotaxime et al.; Laboratoire de Bacteriologie-Virologie, UMR-CNRS 7565, Faculte de Medecine, 54500 Vandoeuvre-les-Nancy, FranceOBJECTIVES: To evaluate the antibiotic susceptibilities of Propionibacterium acnes isolates from central nervous system (CNS) infections to agents used in current treatment regimens . METHODS: MICs of 16 reference antibiotics were determined by an agar dilution method for 24 consecutive strains of P . acnes isolated from individual patients with intracranial empyema or brain abscess . Bactericidal activities of antibiotics against P . acnes PAN14 were studied at 0.25-2 x MIC using a time-kill method . RESULTS: All of the isolates were resistant to fosfomycin, intermediate or resistant to metronidazole and susceptible to all the other antibiotics tested, except for nine strains, which were intermediate to ofloxacin . Among antibiotics tested alone in time-kill experiments, vancomycin was the most effective drug and exhibited bactericidal activity after 24 h at 1x and 2 x MIC, whereas cefotaxime and ciprofloxacin were bactericidal after 48 h at 2 x MIC . No significant bactericidal activity could be demonstrated with the other antibiotics tested alone . The addition of cefotaxime to vancomycin resulted in bactericidal activity at lower concentrations (0.5 x MIC), whereas synergy was observed between quinupristin/dalfopristin and cefotaxime at 2 x MIC . In contrast, antagonism was observed between cefotaxime and linezolid, and ciprofloxacin and clindamycin . CONCLUSION: Our data suggest that P . acnes isolates causing CNS infections remain highly susceptible to most antibiotics used for the treatment of such infections . Moreover, we showed that cefotaxime, vancomycin and ciprofloxacin possess good bactericidal activities against P . acnes, and that these activities may be enhanced when vancomycin is combined with cefotaxime or when cefotaxime is combined with quinupristin/dalfopristin.

Health Technol Assess, 2005 Jan, 9(1), 1 - 212
Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne; Ozolins M et al.; OBJECTIVES: To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains . DESIGN: This was a parallel group randomised assessor-blind controlled clinical trial . It was a pragmatic design with intention-to-treat analysis . All treatments were given for 18 weeks, after a 4-week treatment free period . Outcomes were measured at 0, 6, 12 and 18 weeks . SETTING: Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England . PARTICIPANTS: Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face . INTERVENTIONS: Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR(R) (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin(R) (3% erythromycin + 5% benzoyl peroxide) b.d . + oral placebo o.d.; topical Stiemycin(R) (2% erythromycin) o.d . + topical Panoxyl(R) Aquagel (5% benzoyl peroxide) o.d . + oral placebo o.d., and topical Panoxyl(R) Aquagel (5% benzoyl peroxide) b.d . + oral placebo o.d . (the active comparator group) . MAIN OUTCOME MEASURES: The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots) . RESULTS: The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d . or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small . The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 {95% confidence interval (CI) 1.04 to 2.90} . Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor . Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039) . The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost . For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks . Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline . The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria . The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria . None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains . Systemic adverse events were more common with the two oral antibiotics . Local irritation was more common with the topical treatments, particularly benzoyl peroxide . Residual acne was present in most participants (95%) at the end of the study . CONCLUSIONS: The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal . Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly . Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks . Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy . Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne . The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance . Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions . It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life . There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective . The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face . Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e . what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability).

Appl Environ Microbiol, 2004 Dec, 70(12), 7561 - 6
Effects of expression of hemA and hemB genes on production of porphyrin in Propionibacterium freudenreichii; Piao Y et al.; The genus Propionibacterium has a wide range of probiotic activities that are exploited in dairy and fermentation systems such as cheeses, propionic acid, and tetrapyrrole compounds . In order to improve production of tetrapyrrole compounds, we expressed the hemA gene, which encodes delta-aminolevulinic acid (ALA) synthase from Rhodobacter sphaeroides, and the hemB gene, which encodes porphobilinogen (PBG) synthase from Propionibacterium freudenreichii subsp . shermanii IFO12424, either monocistronically or polycistronically in strain IFO12426 . The recombinant strains accumulated larger amounts of ALA and PBG, with resultant 28- to 33-fold-higher production of porphyrinogens, such as uroporphyrinogen and coproporphyrinogen, than those observed in strain IFO12426, which harbored the shuttle vector pPK705.

Appl Environ Microbiol, 2004 Dec, 70(12), 7303 - 10
Molecular and genetic characterization of propionicin F, a bacteriocin from Propionibacterium freudenreichii; Brede DA et al.; This work describes the purification and characterization of propionicin F, the first bacteriocin isolated from Propionibacterium freudenreichii . The bacteriocin has a bactericidal activity and is only active against strains of P . freudenreichii . Propionicin F appears to be formed through a processing pathway new to bacteriocins . The mass of the purified bacteriocin was determined by mass spectrometry, and the N-terminal amino acid sequence was determined by Edman degradation . Sequencing of pcfA, the bacteriocin structural gene, revealed that propionicin F corresponds to a 43-amino-acid peptide in the central part of a 255-amino-acid open reading frame, suggesting that mature propionicin F is excised from the probacteriocin by N- and C-terminal proteolytic modifications . DNA sequencing and Northern blot hybridizations revealed that pcfA is cotranscribed with genes encoding a putative proline peptidase and a protein from the radical S-adenosylmethionine family . A gene encoding an ABC transporter was also identified in close proximity to the bacteriocin structural gene . The potential role of these genes in propionicin F maturation and secretion is discussed.

Clin Dermatol, 2004 Sep-Oct, 22(5), 398 - 407
Acne: topical treatment; Krautheim A et al.; Acne vulgaris is a common skin disease, affecting about 70-80% of adolescents and young adults . It is a multifactorial disease of the pilosebaceous unit.(1) The influence of androgens at the onset of adolescence leads to an enlargement of the sebaceous gland and a rise in sebum production . Additional increased proliferation and altered differentiation of the follicular epithelium eventually blocks the pilosebaceous duct, leading to development of the microcomedo as the primary acne lesion . Concomitantly and subsequently, colonization with Propionibacterium acnes increases, followed by induction of inflammatory reactions from bacteria, ductal corneocytes, and sebaceous proinflammatory agents (Fig 1).(2-5)

Clin Dermatol, 2004 Sep-Oct, 22(5), 380 - 4
Acne: inflammation; Farrar MD et al.; The inflammatory stage of acne vulgaris is usually of greatest concern to the patient . A number of morphologically different inflammatory lesions may form that can be painful and unsightly . In 30% of patients, such lesions lead to scarring(1) . Inflammatory acne and acne scarring can have significant psychological effects on the patient, including depression, anxiety, and poor self-image(2) . Although inflammatory acne has been well characterized clinically, the mechanisms by which inflammatory lesions arise are still poorly understood . The human skin commensal bacterium, Propionibacterium acnes, has long been associated with inflammatory acne . This organism has been implicated over and above all of the other cutaneous microflora in contributing to the inflammatory response characteristic of acne . However, its precise role in the disease and its interaction with the human immune system remain to be elucidated.

Clin Dermatol, 2004 Sep-Oct, 22(5), 360 - 6
Acne and sebaceous gland function; Zouboulis CC; The embryologic development of the human sebaceous gland is closely related to the differentiation of the hair follicle and the epidermis . The number of sebaceous glands remains approximately the same throughout life, whereas their size tends to increase with age . The development and function of the sebaceous gland in the fetal and neonatal periods appear to be regulated by maternal androgens and by endogenous steroid synthesis, as well as by other morphogens . The most apparent function of the glands is to excrete sebum . A strong increase in sebum excretion occurs a few hours after birth; this peaks during the first week and slowly subsides thereafter . A new rise takes place at about age 9 years with adrenarche and continues up to age 17 years, when the adult level is reached . The sebaceous gland is an important formation site of active androgens . Androgens are well known for their effects on sebum excretion, whereas terminal sebocyte differentiation is assisted by peroxisome proliferator-activated receptor ligands . Estrogens, glucocorticoids, and prolactin also influence sebaceous gland function . In addition, stress-sensing cutaneous signals lead to the production and release of corticotrophin-releasing hormone from dermal nerves and sebocytes with subsequent dose-dependent regulation of sebaceous nonpolar lipids . Among other lipid fractions, sebaceous glands have been shown to synthesize considerable amounts of free fatty acids without exogenous influence . Sebaceous lipids are responsible for the three-dimensional skin surface lipid organization . Contributing to the integrity of the skin barrier . They also exhibit strong innate antimicrobial activity, transport antioxidants to the skin surface, and express proinflammatory and anti-inflammatory properties . Acne in childhood has been suggested to be strongly associated with the development of severe acne during adolescence . Increased sebum excretion is a major factor in the pathophysiology of acne vulgaris . Other sebaceous gland functions are also associated with the development of acne, including sebaceous proinflammatory lipids; different cytokines produced locally; periglandular peptides and neuropeptides, such as corticotrophin-releasing hormone, which is produced by sebocytes; and substance P, which is expressed in the nerve endings at the vicinity of healthy-looking glands of acne patients . Current data indicate that acne vulgaris may be a primary inflammatory disease . Future drugs developed to treat acne not only should reduce sebum production and Propionibacterium acnes populations, but also should be targeted to reduce proinflammatory lipids in sebum, down-regulate proinflammatory signals in the pilosebaceous unit, and inhibit leukotriene B(4)-induced accumulation of inflammatory cells . They should also influence peroxisome proliferator-activated receptor regulation . Isotretinoin is still the most active available drug for the treatment of severe acne.

J Cosmet Laser Ther, 2004 Sep, 6(3), 156 - 62
420 nm intense continuous light therapy for acne; Omi T et al.; BACKGROUND: Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy . However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity . Describe here is a high-intensity, narrow-band, blue light (ClearLight) system, and its therapeutic clinical effect is investigated on acne using cutaneous measurements, bacterial observations and ultrastructural changes . MATERIALS AND METHODS: A total of 28 adult healthy volunteers with facial acne (mean age 28.1 years, range 16-56 years) were recruited for this study . They were treated with a total of eight serial biweekly 15-minute treatment sessions . Clinical counts of acne, as well as moisture, sebum and pH measurements were taken between each session . Nine of the 28 patients were followed for 2-3 months after the last treatment . Detection of bacteria in acne pustules was analyzed by culture and by polymerase chain reaction (PCR) . Ultrastructural changes were examined in eight patients after four sessions of the light therapy . RESULTS: All patients completed the study . Overall, there was a 64.7% improvement in acne lesions . There were no bacterial changes before or after the therapy, although damaged Propionibacterium acnes were observed at the ultrastructural level . CONCLUSIONS: ClearLight performed eight times over 4 weeks can be useful in the treatment of acne . Further investigation will be needed to elucidate the mechanism of action of ClearLight.

Am J Ophthalmol, 2004 Nov, 138(5), 878 - 9
Propionibacterium acnes endophthalmitis with bacterial sequestration in a Molteno's implant after cataract extraction; Hollander DA et al.; PURPOSE: To report a case of Propionibacterium acnes endophthalmitis following uncomplicated cataract extraction with bacterial sequestration in a preexisting Molteno's drainage implant . DESIGN: Interventional case report . METHODS: A 7-year-old girl with congenital glaucoma and a preexisting Molteno's drainage implant developed anterior nongranulomatous uveitis 4 months following cataract surgery . P . acnes endophthalmitis was diagnosed by polymerase chain reaction, Southern blot, and electron microscopy . RESULTS: Extraction of the Molteno's implant was required to control the persistent intraocular inflammation and to convert the results of polymerase chain reaction and Southern blot testing of aqueous sample for P . acnes from positive to negative . CONCLUSION: P . acnes may be sequestered in glaucoma implants, potentially requiring implant removal to treat cases of P . acnes endophthalmitis.

Med Dosw Mikrobiol, 2004, 56(1), 79 - 92
{Characteristics of the Propionibacterium strains isolated from acne patients}; Bialecka A et al.; Propionibacterium acnes is a component of physiological flora of human skin . It colonizes the outlets of sebaceous glands and participates in the pathogenesis of inflammatory acne . Acne vulgaris is a common skin disease . It is found in more or less exacerbated form in approximately 85% of adolescent population . The main purpose of the research was to confirm the hypothesis of Propionibacterium bacteria participation in the aetiopathogenesis of acne vulgaris . The researches have proved the presence of Propionibacterium acnes on the surface of the skin both of people with acne-related changes and these with whom such changes were not found . Statistically significant differences were found in the number of P . acnes bacteria per 1 square centimeter of healthy and disease-affected skin as well as in the diversity of biochemical types . The highest number of P . acnes bacteria have been found in fresh changes with visible symptoms of inflammation . In order to confirm the hypothesis of the participation of Propionibacterium bacteria in the aetiopathogenesis of acne, a detailed phenotypical analysis of isolated P . acnes strains have been conducted . Type, biotype, resistance pattern, proteolytic and lipolytic properties have been determined.

In Silico Biol . 2004 Sep 28;4(3):0043 {Epub ahead of print}
In silico exploration of the fructose-6-phosphate phosphorylation step in glycolysis: genomic evidence of the coexistence of an atypical ATP-dependent along with a PPi-dependent phosphofructokinase in Propionibacterium freudenreichii subsp . shermanii; Meurice G et al.; We performed a detailed bioinformatic study of the catalytic step of fructose-6-phosphate phosphorylation in glycolysis based on the raw genomic draft of Propionibacterium freudenreichii subsp . shermanii (P . shermanii) ATCC9614 {Meurice et al., 2004} . Our results provide the first in silico evidence of the coexistence of genes coding for an ATP-dependent phosphofructokinase (ATP-PFK) and a PPi-dependent phosphofructokinase (PPi-PFK), whereas the fructose-1,6-bisphosphatase (FBP) and ADP-dependent phosphofructokinase (ADP-PFK) are absent . The deduced amino acid sequence corresponding to the PPi-PFK (AJ508922) shares 100% similarity with the already characterised propionibacterial protein (P29495; Ladror et al., 1991} . The unexpected ATP-PFK gene (AJ509827) encodes a protein of 373 aa which is highly similar (50% positive residues) along at least 95% of its sequence length to different well-characterised ATP-PFKs . The characteristic PROSITE pattern important for the enzyme function of ATP-PFKs (PS00433) was conserved in the putative ATP-PFK sequence: 8 out of 9 amino acid residues . According to the recent evolutionary study of PFK proteins with different phosphate donors {Bapteste et al., 2003}, the propionibacterial ATP-PFK harbours a G104-K124 residue combination, which strongly suggested that this enzyme belongs to the group of atypical ATP-PFKs . According to our phylogenetic analyses the amino acid sequence of the ATP-PFK is clustered with the atypical ATP-PFKs from group III of the Siebers classification {Siebers et al., 1998}, whereas the expected PPi-PFK protein is closer to the PPi-PFKs from clade P {Mueller et al., 2001} . The possible significance of the co-existence of these two PFKs and their importance for the regulation of glycolytic pathway flux in P . shermanii is discussed.

Eur J Ophthalmol, 2004 Sep-Oct, 14(5), 442 - 4
Late onset posttraumatic Propionibacterium acnes endophthalmitis; El-Asrar AM et al.; PURPOSE: To report a case of late onset posttraumatic endophthalmitis secondary to Propionibacterium acnes infection . METHODS: Interventional case report . RESULTS: A 28-year-old man developed endophthalmitis 6 months after a penetrating trauma . The patient underwent pars plana lensectomy and vitrectomy along with injection of intravitreal antibiotics . Anaerobic cultures of the vitreous yielded P . acnes . Seven months after surgery, the eye was quiet with a best-corrected visual acuity of 20/60 . CONCLUSIONS: This case emphasizes the importance of considering P acnes when treating patients with late onset posttraumatic endophthalmitis.

Cutis, 2004 Sep, 74(3), 189 - 92
The pathophysiology of acne vulgaris in children and adolescents, part 2: Tailoring treatment; Bergfeld WF; Various pathophysiologic factors are involved in the development of acne lesions, microcomedones, comedones, and inflammatory lesions . These factors include follicular hyperkeratosis, increased colonization of follicles by Propionibacterium acnes, increased sebum production, and inflammatory mediators . Optimal treatment of acne involves the use of agents that address these various underlying pathogenetic factors.

Drugs, 2004, 64(21), 2389 - 97
Topical antibacterial therapy for acne vulgaris; Dreno B; Topical antibiotics and benzoyl peroxide, are the two main topical antibacterial treatments indicated for mild-to-moderate acne vulgaris . Topical antibiotics act both as antibacterial agents suppressing Propionibacterium acnes in the sebaceous follicle and as anti-inflammatory agents . Benzoyl peroxide is a powerful antimicrobial agent that rapidly destroys both bacterial organisms and yeasts . Topical clindamycin and erythromycin have been proven to be effective against inflammatory acne vulgaris in concentrations of 1-4% with or without the addition of zinc . However, none of the antibacterials tested was more effective than benzoyl peroxide, which also has the advantage of not being associated with antimicrobial resistance.Topical antibacterial therapy should be discontinued once improvement is observed . If no improvement is observed within 6-8 weeks, the agent should be discontinued and a therapeutic switch considered . The primary limitation of benzoyl peroxide for some acne vulgaris patients is cutaneous irritation or dryness.Antibacterial therapy can be used in combination with other agents . Combining topical antibiotics and topical retinoids may enhance the efficacy, since the retinoid will improve the penetration of the antibiotic . Combining a topical antibiotic with benzoyl peroxide may increase the bactericidal effect of the antibiotic and reduce the potential for bacterial resistance . Topical and oral antibacterials should not be used in combination for the treatment of acne vulgaris, since this association may increase the risk of bacterial resistance.

Pathobiology, 2004, 71(5), 246 - 52
Involvement of CD14 in lipopolysaccharide- induced liver injury in mice pretreated with Propionibacterium acnes; Uchida T et al.; OBJECTIVE: The aim of this study was to elucidate the role of CD14 in the Propionibacterium acnes-lipopolysaccharide (LPS) system . METHODS AND RESULTS: CD14 transgenic mice (M14M), which expressed heterotopic CD14 and showed decreased responses to LPS in vivo, were used . Seven days after priming, the size of granulomas induced by an intraperitoneal administration of P . acnes in the M14M mice was smaller than that in the nontransgenic mice . The number of CD14-positive cells in granulomas was also decreased in the M14M mice compared to the nontransgenic mice . An LPS challenge induced apoptotic and necrotic changes in hepatocytes in the nontransgenic mice but not in the M14M mice . Seven days after priming, tumor necrosis factor-alpha expression was found in monocytic cells in granulomas and Kupffer cells in the nontransgenic mice and was significantly upregulated after LPS injection, whereas the expression was very weak in these cells in the M14M mice . CONCLUSIONS: CD14 plays a role in the P . acnes-LPS system in both priming and induction phases.

Cutis, 2004 Aug, 74(2), 92 - 7
The pathophysiology of acne vulgaris in children and adolescents, Part 1; Bergfeld WF; Microcomedones, the earliest lesions of acne, appear at adrenarche, which typically occurs at about 8 years of age when androgens of adrenal origin begin to stimulate follicular hyperkeratosis and sebaceous hyperplasia in pilosebaceous units on the face . Comedones appear about 2 years later, when androgens of gonadal origin are produced and colonization of follicles by Propionibacterium acnes increases . Inflammatory lesions, such as pustules, papules, and nodules, are the result of the host's immune responses to P acnes; the proinflammatory cytokines are released by immunocompetent leukocytes that are recruited in response to this bacterium and its metabolic by-products . Androgens also affect the barrier function of the skin, and disturbances of barrier function may stimulate epidermal DNA synthesis . This leads to epidermal hyperplasia, which may also contribute to follicular hyperkeratosis in acne . Optimal treatment for this disorder will address these various pathophysiologic factors.

Br J Dermatol, 2004 Sep, 151(3), 616 - 22
Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action; Pollock B et al.; BACKGROUND: Acne affects 83-95% of 16-year-olds of both sexes, and many seek help from a clinician . Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne . OBJECTIVES: To study the efficacy of aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of acne and to identify the mode of action, looking specifically at the effects on surface numbers of P . acnes and on sebum excretion . METHODS: Ten patients (nine men and one woman, age range 16-40 years) with mild to moderate acne on their backs were recruited . Each patient's back was marked with four 30-cm2 areas of equal acne severity . Each site was then randomly allocated to either ALA-PDT treatment, light alone, ALA alone or an untreated control site . At baseline, numbers of inflammatory and noninflammatory acne lesions were counted, sebum excretion measured by Sebutapes (CuDerm, Dallas, TX, U.S.A.) and surface P . acnes swabs performed . ALA cream (20% in Unguentum Merck) was applied under occlusion to the ALA-PDT and ALA alone sites for 3 h . Red light from a diode laser was then delivered to the ALA-PDT and light alone sites (635 nm, 25 mW cm(-2), 15 J cm(-2)) . Each patient was treated weekly for 3 weeks . At each visit acne lesion counts were performed and 3 weeks following the last treatment sebum excretion rates and P . acnes swabs were repeated . RESULTS: There was a statistically significant reduction in inflammatory acne lesion counts from baseline after the second treatment at the ALA-PDT site but not at any of the other sites . No statistically significant reduction in P . acnes numbers or sebum excretion was demonstrated at any sites including the ALA-PDT site . CONCLUSIONS: ALA-PDT is capable of clinically improving acne . An alternative mode of action for ALA-PDT other than direct damage to sebaceous glands or photodynamic killing of P . acnes is suggested from the results of this study.

Gastroenterology, 2004 Sep, 127(3), 892 - 902
Inducible histamine protects mice from P . acnes-primed and LPS-induced hepatitis through H2-receptor stimulation; Yokoyama M et al.; BACKGROUND & AIMS: Inducible histamine and histamine H2-receptors have been suggested to be involved in innate immune response . METHODS: We examined a functional role of inducible histamine in the protection against hepatic injury and lethality in Propionibacterium acnes -primed and lipopolysaccharide-induced hepatitis, using histidine decarboxylase knockout and H2-receptor knockout mice . RESULTS: Lipopolysaccharide challenge after Propionibacterium acnes priming increased histidine decarboxylase activity in the liver of wild-type mice, associated with a marked elevation of histamine turnover . Histidine decarboxylase-like immunoreactivity was observed in CD68-positive Kupffer cells/macrophages . Treatment of wild-type mice with famotidine or ranitidine but not d -chlorpheniramine augmented hepatic injury and inhibited the survival rate significantly . The same dose of Propionibacterium acnes and lipopolysaccharide induced severe hepatitis and high lethality in histidine decarboxylase knockout and H2-receptor knockout mice; the former were rescued by the subcutaneous injection of histamine . Immunohistochemical study supported the protective role of histamine against the apoptosis of hepatocytes . Histamine suppressed the expression of IL-18 and tumor necrosis factor alpha in the liver, leading to the reduced plasma levels of cytokines including IL-18, TNF-alpha, IL-12, IFN-gamma, and IL-6 . CONCLUSIONS: These findings as a whole indicated that endogenously produced histamine in Kupffer cells/macrophages plays a very important role in preventing excessive innate immune response in endotoxin-induced fulminant hepatitis through the stimulation of H2-receptors.

J Microbiol, 2004 Jun, 42(2), 117 - 25
Antibody response to crude cell lysate of propionibacterium acnes and induction of pro-inflammatory cytokines in patients with acne and normal healthy subjects; Basal E et al.; Propionibacterium acnes (P . acnes) plays an important role in the disease pathogenesis of acne vulgaris, a disorder of pilosebaceous follicles, seen primarily in the adolescent age group . In the present study, the presence of antibodies against P . acnes (MTCC1951) were detected in acne patient (n=50) and disease free controls (n=25) using dot-ELISA and Western blot assay . The ability of P . acnes to induce pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMCs), obtained from acne patients and healthy subjects, were also analysed . The patients (n=26) who were culture positive for skin swab culture, were found to have a more advanced disease and higher antibody titres (1:4000 to > 1:16000) compared to the P . acnes negative patients (n=24) and normal controls (n=25) . An analysis of patients' sera by western blot assay recognized a number of antigenic components of P . acnes, ranging from 29 to 205 kDa . The major reactive component was an approximately 96 kDa polypeptide, which was recognised in 92% (24 of 26) of the patients sera . Further, the P . acnes culture supernatant, crude cell lysate and heat killed P . acnes whole cells, obtained from 72-h incubation culture, were observed to be able to induce significant amounts of IL-8 and tumor necrosis factor alpha (TNF-alpha) by the PBMCs in both the healthy subjects and patients, as analysed by cytokine-ELISA . The levels of cytokines were significantly higher in the patients than the healthy subjects . A major 96 kDa polypeptide reactant was eluted from the gel and was found to cause dose dependent stimulation of the productions of IL-8 and TNF-alpha . Thus, the above results suggest that both humoral and pro-inflammatory responses play major roles in the pathogenesis of acne.

J Dairy Res, 2004 Aug, 71(3), 367 - 71
Influence of manufacturing conditions on the conjugated linoleic acid content and the isomer composition in ripened French Emmental cheese; Gnadig S et al.; In a study of the evolution of conjugated linoleic acid (CLA) during cheese production, the influence of Emmental cheese processing on the CLA content and the CLA isomer composition was evaluated . The use of raw and thermised milk, changes of processing temperature and the effect of propionic acid bacteria (PAB) were investigated . The content of CLA in raw milk was 8.6 +/- 1.9 mg/g fat and in the ripened cheese at 70 d was 8.6 +/- 1.6 mg/g fat, under normal processing conditions . No changes in the CLA content and CLA isomer composition were observed during Emmental cheese manufacturing process . Changes in cooking and moulding temperatures did not influence the CLA content . CLA content of cheese made from microfiltered milk with two different Propionibacterium freudenreichii strains was very close to cheeses made without PAB . CLA levels seem to be stable in this type of dairy product under the conditions examined.

Hepatology, 2004 Sep, 40(3), 555 - 64
Selective priming to Toll-like receptor 4 (TLR4), not TLR2, ligands by P . acnes involves up-regulation of MD-2 in mice; Romics L Jr et al.; Lipopolysaccharide (LPS) triggers cytokine production through Toll-like receptor 4 (TLR4), which shares downstream signaling pathways with TLR2 . We investigated the roles of TLR2 and TLR4 in Propionibacterium acnes (P . acnes)-primed, LPS-induced liver damage using selective TLR ligands . Stock LPS induced interleukin 8 in both TLR4- and TLR2-expressing human embryonic kidney (HEK) 293 cells . Purified LPS (TLR4 ligand) activated HEK/TLR4 cells, while peptidoglycan and lipoteichoic acid (TLR2 ligands) activated HEK/TLR2 cells, respectively . In mice, P . acnes priming resulted in increased liver messenger RNA (mRNA) and serum levels of tumor necrosis factor alpha, interleukin 12, and interferon gamma (IFN-gamma) by both stock LPS and purified LPS challenges compared with nonprimed controls . In contrast, P . acnes failed to sensitize to TLR2 ligands (peptidoglycan + lipoteichoic acid) . In the liver, P . acnes-priming was associated with up-regulation of TLR4 and MD-2 proteins, and subsequent LPS challenge further increased MD-2 and CD14 mRNA levels . The lack of sensitization to TLR2 ligands by P . acnes correlated with no increase in hepatic TLR1 or TLR6 mRNA . In vitro, P . acnes pretreatment desensitized RAW macrophages to a secondary stimulation via both TLR2 and TLR4 . However, IFN-gamma could selectively prevent desensitization to TLR4 but not to TLR2 ligands . Furthermore, P . acnes induced production of IFN-gamma in vivo as well as in isolated splenocytes . In vitro, P . acnes-primed Hepa 1-6 hepatocytes but not RAW macrophages produced increased MD-2 and CD14 mRNA levels after an LPS challenge . In conclusion, P . acnes priming to selective TLR4-mediated liver injury is associated with up-regulation of TLR4 and MD-2 and is likely to involve IFN-gamma and prevent TLR4 desensitization by P . acnes .

Eur J Pediatr Surg, 2004 Aug, 14(4), 245 - 9
Distal catheter obstruction from non-infectious cause in ventriculo-peritoneal shunted children; Arnell K et al.; In hydrocephalic children, ventriculo-peritoneal shunting is the preferred treatment with few complications . However, an obviously non-infectious peritoneal reaction to the cerebrospinal fluid (CSF) may occasionally lead to shunt malfunction . In eight hydrocephalic children, shunt malfunction with distal catheter complication was found with abdominal pseudocyst formation in seven cases and accumulation of the CSF in one . All children had a normal CSF cell count and glucose concentration, and white cell count, and C-reactive protein in peripheral blood were normal . No CSF infection could be detected despite prolonged aerobic and anaerobic cultures . After initial externalisation of the shunt and subsequent routine administration of antibiotics because infection initially was suspected, ventriculo-peritoneal shunting was attempted one to three times with identical failure before successful conversion to a ventriculo-atrial system . At laparotomy the peritoneum and intestinal serosa were hyperaemic and oedematous in all patients, five of whom also had pseudocysts and two of whom also had intra-abdominal adhesions . Four children had a revision 6-24 years after the ventriculo-atrial conversion due to short atrial catheter with distal obstruction . In three of them, the distal catheter was successfully replaced into the peritoneal cavity . The fourth child, however, developed an infectious abdominal pseudocyst with adhesions due to a then undetected Propionibacterium acnes infection . After externalisation and antibiotics, a new ventriculo-atrial shunt was inserted . At follow-up between 5 months to nearly 6 years later, the three children with peritoneal catheters did not show any signs of shunt malfunction or abdominal problems . Thus hydrocephalic children may develop shunt malfunction with distal catheter obstruction due to a still unexplained, transient, non-infectious peritoneal reaction leading to abdominal pseudocyst formation or accumulation of CSF . In some children, however, it may later be possible to replace the distal catheter into the peritoneal cavity, if no infection is involved.

EMBO J, 2004 Sep 15, 23(18), 3621 - 31 Epub 2004 Aug 26.
Transcarboxylase 5S structures: assembly and catalytic mechanism of a multienzyme complex subunit; Hall PR et al.; Transcarboxylase is a 1.2 million Dalton (Da) multienzyme complex from Propionibacterium shermanii that couples two carboxylation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate to yield propionyl-CoA and oxaloacetate . Crystal structures of the 5S metalloenzyme subunit, which catalyzes the second carboxylation reaction, have been solved in free form and bound to its substrate pyruvate, product oxaloacetate, or inhibitor 2-ketobutyrate . The structure reveals a dimer of beta(8)alpha(8) barrels with an active site cobalt ion coordinated by a carbamylated lysine, except in the oxaloacetate complex in which the product's carboxylate group serves as a ligand instead . 5S and human pyruvate carboxylase (PC), an enzyme crucial to gluconeogenesis, catalyze similar reactions . A 5S-based homology model of the PC carboxyltransferase domain indicates a conserved mechanism and explains the molecular basis of mutations in lactic acidemia . PC disease mutations reproduced in 5S result in a similar decrease in carboxyltransferase activity and crystal structures with altered active sites.

J Cataract Refract Surg, 2004 Aug, 30(8), 1790 - 4
Unusual anaerobic bacteria in keratitis after laser in situ keratomileusis: diagnosis using molecular biology methods; Ferrer C et al.; Laser in situ keratomileusis (LASIK) was performed in the left eye of a 57-year-old man for residual ametropia after phacoemulsification . The patient was given topical tobramycin and a corticosteroid for 1 week postoperatively . Fifteen days later, he developed 3 corneal infiltrates beneath the flap with a gas bubble, suggesting an anaerobic infection . Tobramycin and ofloxacin were administered every 2 hours, but the condition worsened . Corneal scrapings were taken from beneath the flap for microbiological cultures and a polymerase chain reaction (PCR) test . The PCR amplification was negative for fungi and mycobacteria and positive for bacterial DNA . Sequence analysis showed Propionibacterium granulosum as the causal agent, but cultures were negative . Treatment with vancomycin and cefazolin led to clinical improvement, with resolution of corneal infiltrates . Anaerobic microorganisms can cause keratitis after LASIK . Polymerase chain reaction amplification and DNA typing can help detect microorganisms involved in these ocular infections.

Heart . 2004 Sep;90(9):e56.
Propionibacterium acnes endocarditis on an annuloplasty ring in an adolescent boy; Vanagt WY et al.; Propionibacterium acnes, a constituent of the human cutaneous flora, infected both the native mitral valve and a Carpentier mitral annuloplasty ring in an adolescent patient . In the case of culture negative endocarditis, the incubation period of blood cultures should be prolonged to identify this pathogen.

Appl Biochem Biotechnol, 1999 Feb, 76(2), 99 - 106
On-Line Dialysis of Organic Acids from a Propionibacterium freudenreichii Fermentation: Evaluation of a New pH Control Strategy; Da Costa JP et al.; The efficiency of an ion exchange system coupled to a bioreactor to extract on-line inhibitory organic acids produced was evaluated . Batch fermentations without dialysis and fed-batch experiments with and without dialysis of Propionibacterium freudenreichii were conducted . It was possible to keep the propionic acid concentration in the reactor at a low level to avoid complete growth inhibition . Improvements in biomass and propionic acid productivities were achieved when the dialysis system was used . The performance of the dialysis system was improved when a new pH control strategy evaluated in this study was used.

Am J Clin Dermatol, 2004, 5(4), 261 - 5
Benzoyl peroxide-based combination therapies for acne vulgaris: a comparative review; Taylor GA et al.; Benzoyl peroxide, with its broad-spectrum antimicrobial activity, is among the most widely used topical agents in the treatment of inflammatory acne vulgaris . Benzoyl peroxide is marketed either alone or in combination with other topical antibiotics; namely, erythromycin and clindamycin . The combination products confer specific advantages over benzoyl peroxide alone, particularly in decreasing the in vivo follicular counts of Propionibacterium acnes, the anaerobic bacterium implicated in the pathogenesis of acne . In addition, the topical treatment of inflammatory acne has been complicated by the development of P acnes resistance to topical erythromycin and clindamycin . Combination products containing benzoyl peroxide and the topical antibiotics have been shown to both: (i) prevent the development of antibiotic resistance in acne patients; and (ii) confer significant clinical improvement to patients who have already developed antibiotic resistance.

Eur J Pharmacol, 2004 Aug 2, 496(1-3), 189 - 95
In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp; Park J et al.; Honokiol and magnolol, two major phenolic constituents of Magnolia sp., have been known to exhibit antibacterial activities . However, until now, their antibacterial activity against Propionibacterium sp . has not been reported . To this end, the antibacterial activities of honokiol and magnolol were detected using the disk diffusion method and a two-fold serial dilution assay . Honokiol and magnolol showed strong antibacterial activities against both Propionibacterium acnes and Propionibacterium granulosum, which are acne-causing bacteria . The minimum inhibitory concentrations (MIC) of honokiol and magnolol was 3-4 microg/ml (11.3-15 microM) and 9 microg/ml (33.8 microM), respectively . In addition, the killing curve analysis showed that magnolol and honokiol killed P . acnes rapidly, with 10(5) organisms/ml eliminated within 10 min of treatment with either 45 microg (169.2 microM) of magnolol or 20 microg (75.2 microM) of honokiol per ml . The cytotoxic effect of honokiol and magnolol was determined by a colorimetric (3-(4,5-dimetyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay using two animal cell lines, human normal fibroblasts and HaCaT . In this experiment, magnolol exhibited lower cytotoxic effects than honokiol at the same concentration, but they showed similar cytotoxicity when triclosan was employed as an acne-mitigating agent . In addition, they reduced secretion of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) induced by P . acnes in THP-1 cells indicating the anti-inflammatory effects of them . When applied topically, neither phenolic compound induced any adverse reactions in a human skin primary irritation test . Therefore, based on these results, we suggest the possibility that magnolol and honokiol may be considered as attractive acne-mitigating candidates for topical application.

Science, 2004 Jul 30, 305(5684), 671 - 3
The complete genome sequence of Propionibacterium acnes, a commensal of human skin; Bruggemann H et al.; Propionibacterium acnes is a major inhabitant of adult human skin, where it resides within sebaceous follicles, usually as a harmless commensal although it has been implicated in acne vulgaris formation . The entire genome sequence of this Gram-positive bacterium encodes 2333 putative genes and revealed numerous gene products involved in degrading host molecules, including sialidases, neuraminidases, endoglycoceramidases, lipases, and pore-forming factors . Surface-associated and other immunogenic factors have been identified, which might be involved in triggering acne inflammation and other P . acnes-associated diseases.

Am J Pathol, 2004 Aug, 165(2), 631 - 9
Indigenous pulmonary Propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice; Nishiwaki T et al.; Although many cases of sarcoidosis are self-limiting with spontaneous remission, uncontrolled pulmonary granulomatosis with fibrosis produces intolerable long-term respiratory symptoms in a minority of patients . Individuals with chronic pulmonary sarcoidosis require an alternative therapy to corticosteroidal treatment because of its insufficient effectiveness . Although many researchers have considered infection as the triggering factor for this disease, the mechanisms by which the candidate causative organisms induce this disorder remain unclear . We report here that extrapulmonary sensitization to Propionibacterium acnes, which is one of the candidates to date, induced pulmonary Th-1 granulomas mainly in the subpleural and peribronchovascular regions often observed in sarcoidosis . These granulomas appear to be caused by indigenous P . acnes pre-existing in the lower respiratory tract of the normal lung, which is believed to be germ-free, and by an influx of P . acnes-sensitized CD4(+) T cells from the circulation . Importantly, the eradication of indigenous P . acnes with antibiotics alleviated the granulomatous lung disease . This is the first report to present clear evidence of the contribution of an indigenous pulmonary bacterium to the formation of granulomatous lesions in the lung . We propose that treatment targeting indigenous P . acnes in the lung may be a possible remedy for pulmonary sarcoidosis.

Scand J Clin Lab Invest, 2004, 64(5), 451 - 6
Biosynthesis of 32P-labelled hydroxocobalamin and a study of its behaviour in rats; Grasbeck R et al.; Using Propionibacterium freudenreichii and 32P-ATP, batches of 32P-labelled cobalamin (Cbl) were biosynthesized with a maximum specific activity of 61 microCi/mg, i.e . about 100 times higher than previously reported . Pharmacological doses mixed with 57Co-Cbl were injected subcutaneously in the form of hydroxo-Cbl into rats subsequently killed 5-20 days later . The two labelled Cbls were distributed in approximately the same way, the highest concentration being found in kidney (typical for rats) and about one-fifth of that in liver . These findings tallied with previous observations with radioactive cyano-Cbl and microbiological assay . In all injected rats, the 57Co/32P ratio was lower in liver than in kidney . Drugs eradicating the intestinal flora had no influence . In rats receiving the vitamin orally, the ratio was higher in liver than in kidney . All of our findings could be due to formation of a cobinamide-like compound lacking phosphorus . It is concluded that we have produced radiophosphorus-labelled Cbl that enables studies in vivo.

Curr Opin Pediatr, 2004 Aug, 16(4), 385 - 91
Acne update: 2004; Smolinski KN et al.; PURPOSE OF REVIEW: Acne vulgaris is a common skin disorder among children and young adults that carries enormous financial and psychosocial impact . Contemporary therapies attempt to address factors underlying acne as a disorder of the pilosebaceous unit . These longstanding paradigms regarding pathogenesis and treatment continue to evolve in light of recent work on this ubiquitous disease . RECENT FINDINGS: This review focuses on new literature that has emerged regarding the biology of the folliculosebaceous unit, the identification of particular mediators responsible for inflammatory acne, the use of topical and systemic retinoids in acne therapy, and approaches to address the emergence of antibiotic-resistant Propionibacterium acnes strains . In addition, the use of several novel therapeutic avenues is discussed, including combination therapies, lipoxygenase inhibitors, and lasers . SUMMARY: As the understanding of the factors that initiate and exacerbate acne vulgaris continues to increase, so does the diversity of therapeutic options . Rational use of available treatment options based on the type and severity of acne lesions is a key component of successful acne therapy and allows the physician who treats adolescents with acne to provide optimum care.

J Clin Neurosci, 2004 Aug, 11(6), 677 - 9
Propionibacterium acnes causing delayed subdural empyema - a case report and review of literature; Ghalayini SR et al.; The authors report a patient who presented with a delayed subdural empyema caused by Propionibacterium acnes following excision of a meningioma . This organism should be suspected in all patients with delayed empyema especially in the presence of implants and immunosuppression . The main features of this pathogen is discussed . Surgical drainage and high-dose intravenous penicillin should be the recommended therapy.

Immunol Lett, 2004 Jun 15, 94(1-2), 47 - 55
Roles of CD14 in LPS-induced liver injury and lethality in mice pretreated with Propionibacterium acnes; Shuto Y et al.; The mechanism of the liver damage and lethality in Propionibacterium acnes (P . acnes)-LPS system remains obscure . To examine the role of CD14 in the system, M14M mice, in which CD14 was expressed heterotopically under the control of the metallothionein promoter were used . The production of soluble CD14 (sCD14) was increased by both P . acnes - priming and LPS challenge (1 microg per mouse) in both nontransgenic and M14M mice, although the plasma level was much higher in M14M nontransgenic than mice . The size of granulomas induced by an intraperitoneal administration of P . acnes in M14M mice 7 days after priming was smaller than that in nontransgenic mice . An LPS challenge induced apoptotic and necrotic changes in hepatocytes in nontransgenic mice but not in M14M mice . The challenge dose resulted in almost 90% lethality in nontransgenic mice but not in M14M mice 24h after challenge . TNF-alpha, IFN-gamma, IL-12, IL-18 and inducible nitric oxide synthase (iNOS) mRNA expressions produced by LPS challenge in M14M mice were low compared with those in nontransgenic mice . IL-18 mRNA expression was upregulated in P . acnes-primed nontransgenic mice but not in M14M mice . These results suggest that the high sCD14 concentration may account for less marked liver damage in M14M mice . Increase in the challenge dose of LPS (2 microg per mouse) resulted in increased lethality of M14M mice without liver damage . The levels of endothelial cell leukocyte adhesion molecule (ELAM)-1 mRNA expression in several organs in M14M mice 1-3h after LPS challenge were, however, lower than those in nontransgenic mice . The high sCD14 concentration may stimulate endothelial cell activation, which may account for lethality without liver damage in M14M mice . Thus, CD14 is involved in both the priming and induction phases as well as lethality in P . acnes-LPS system.

Cutis, 2004 Jun, 73(6 Suppl), 6 - 10
Antibiotic resistance in the topical treatment of acne vulgaris; Leyden JJ; Topical antimicrobial agents are the first line of treatment in mild to moderate acne vulgaris . The primary pathogenic agent implicated in the development of inflammatory acne is Propionibacterium acnes . P acnes also may play a secondary role in noninflammatory acne or comedogenesis . Over the past 20 years, concern has grown about the gradual worldwide increase in the prevalence of antibiotic-resistant P acnes strains . Factors associated with the development of resistant P acnes following treatment with topical antibiotics, clinical relevance of antibiotic resistance, and strategies to reduce the incidence of P acnes resistance are discussed in this review.

J Cosmet Laser Ther, 2004 Jun, 6(2), 91 - 5
The role of pulsed light and heat energy (LHE) in acne clearance; Elman M et al.; BACKGROUND: Propionibacterium acnes synthesize and store a large amount of porphyrins . Once the porphyrin is exposed to visible light it becomes chemically active and transfers to an excited state, resulting in the formation of singlet oxygen, which combines with cell membranes to destroy the P . acnes . This process is dependent on the rate of production of excited porphyrin molecules, which is influenced by the concentration of porphyrins, the concentration of photons, the temperature, and the wavelength of the photons . METHODS: Nineteen patients with mild to moderate acne underwent bi-weekly treatments for 4 weeks using the ClearTouch system . During each treatment, pulses of light and heat were applied . Each pulse used an average energy density of 3.5 J/cm(2), a pulse width of 35 ms, and a wavelength between 430 and 1100 nm . RESULTS: At the end of the eighth treatment, acne clearance for the non-inflammatory and inflammatory lesions was 63 +/- 21% and 50 +/- 32%, respectively . One month after the last treatment, the acne clearance for non-inflammatory and inflammatory lesions was 79 +/- 22% and 74 +/- 20%, respectively, with further improvement in acne clearance at 2 months after the last treatment (85 +/- 17% and 87 +/- 25%, respectively) . CONCLUSION: ClearTouch pulsed light and heat energy (LHE) technology is effective and safe for the treatment of acne vulgaris.

J Eur Acad Dermatol Venereol, 2004 Jul, 18(4), 450 - 4
Evidence for diversity within Propionibacterium acnes: a comparison of the T-cell stimulatory activity of isolates from inflammatory acne, endocarditis and the laboratory; Jappe U et al.; BACKGROUND: Propionibacterium acnes is primarily associated with the pathogenesis of acne vulgaris but reports are increasing in number implicating P . acnes in other diseases such as abscess formation, meningitis and endocarditis . The pathogenicity of P . acnes is thought to be partly due to the interaction of the bacterium with the immune system . Historically, investigations have focused on humoral and cell-mediated immune responses to P . acnes antigens without attention to the possibility that different antigens may be expressed by different isolates . OBJECTIVE: Investigations were performed to determine whether there were differences between a laboratory strain of P . acnes (P-37) and fresh clinical isolates in their ability to stimulate naive and adult lymphocytes . MATERIAL AND METHODS: The fresh isolates were collected from a patient with inflammatory acne and a patient with P . acnes-induced prosthetic valve endocarditis . The lymphocyte transformation assay was used to detect responses to whole-cell suspensions of stationary phase P . acnes isolates during 7 days of incubation . RESULTS: The acne isolate was significantly more stimulatory for cord blood mononuclear cells (CBMNCs) than the laboratory isolate (P . acnes P-37) at day 4 of incubation . There were no significant differences between the three strains at any other time points . However, the isolate cultivated from inflammatory acne was significantly more stimulatory for peripheral blood mononuclear cells (PBMNCs) from acne donors than the endocarditis isolate or the laboratory strain at most time points . There were no significant differences between the endocarditis strain and the laboratory strain . CONCLUSION: It can be hypothesized that in case of P . acnes-induced endocarditis lymphocyte stimulation is a disadvantage for the microorganism and therefore a lack of lymphocyte stimulation may be relevant to the pathogenesis of endocarditis.

Org Biomol Chem, 2004 Jun 21, 2(12), 1777 - 81 Epub 2004 May 20.
Determination of the binding specificity of the 12S subunit of the transcarboxylase by saturation transfer difference NMR; Peikert C et al.; In this study we present the characterization of the interaction of biotin and methylmalonyl-CoA (MMCoA) with the carboxyltransferase subunit (12S) from the transcarboxylase (TC) from Propionibacterium shermanii . This biotin dependent multienzyme complex catalyses the transfer of carbon dioxide from methylmalonyl-CoA (MMCoA) to pyruvate . The Saturation Transfer Difference NMR (STD) technique was performed to determine the binding epitope from biotin and MMCoA to the 12S subunit . We could show by titrations during STD experiments that biotin and MMCoA bind cooperatively in one binding pocket.

Int J Dermatol, 2004 Feb, 43(2), 103 - 7
Propionibacterium acnes biotypes and susceptibility to minocycline and Keigai-rengyo-to; Higaki S et al.; BACKGROUND: Propionibacterium acnes is the predominant organism in acne lesions, but the sensitivity of different biotypes of P . acnes to therapeutic agents has seldom been reported . METHODS: To characterize biotypes of P . acnes and to measure the effects of Keigai-rengyo-to (KRT) and minocycline (MINO) on clinical P . acnes isolates . RESULTS: Propionibacterium acnes biotype III (BIII) is the most common form of identified acne lesion, followed by P . acnes biotype I . BIII was isolated from mild, moderate and severe severity and the average lipase activity of BIII was higher than that of Biotypes I, II, IV and V . No significant differences in the decrease of free fatty acid production elicited by KRT or by MINO were found between BIII and the other biotypes . The degree of decreased butyric acid production was greater than that of propionic acid production in the medium supplemented with MINO . The percent decrease of butyric acid production elicited by 1 mg/mL of KRT was the same as that elicited by 0.1 microg/mL of MINO . Among biotypes of P . acnes, the minimal inhibitory concentrations of agents tested were generally higher in erythritol-positive biotypes than in erythritol-negative biotypes . CONCLUSION: The high frequency of BIII might be responsible for the severity of acne in patients . It seems that if the same concentrations of MINO and KRT are used, the antilipase activity of MINO is stronger than that of KRT . Minocycline also has a direct anti-lipase activity against P . acnes . The mechanism underlying the influence of erythritol on the susceptibility of P . acnes to these agents remains unknown.

Am J Clin Dermatol, 2004, 5(2), 79 - 84
Topical antibacterial treatments for acne vulgaris : comparative review and guide to selection; Tan HH; Topical antibacterial agents are an essential part of the armamentarium for treating acne vulgaris . They are indicated for mild-to-moderate acne, and are a useful alternative for patients who cannot take systemic antibacterials . Topical antibacterials such as clindamycin, erythromycin, and tetracycline are bacteriostatic for Propionibacterium acnes, and have also been demonstrated to have anti-inflammatory activities through inhibition of lipase production by P . acnes, as well as inhibition of leukocyte chemotaxis . Benzoyl peroxide is a non-antibiotic antibacterial agent that is bactericidal against P . acnes and has the distinct advantage that thus far, no resistance has been detected against it . Combined agents such as erythromycin/zinc, erythromycin/tretinoin, erythromycin/isotretinoin, erythromycin/benzoyl peroxide, and clindamycin/benzoyl peroxide are increasingly being used and have been proven to be effective . They generally demonstrate good overall tolerability and are useful in reducing the development of antibacterial resistance in P . acnes . The selection of a topical antibacterial agent should be tailored for specific patients by choosing an agent that matches the patient's skin characteristics and acne type . Topical antibacterial agents should generally not be used for extended periods beyond 3 months, and topical antibacterials should ideally not be combined with systemic antibacterial therapy for acne; in particular, the use of topical and systemic antibacterials is to be avoided as far as possible.

Antonie Van Leeuwenhoek, 2004 Jul, 86(1), 77 - 85
Purification and characterisation of lipoglycan macroamphiphiles from Propionibacterium acnes; Whale GA et al.; Lipidated macroamphiphiles such as the lipoteichoic acids and mycobacterial lipoarabinomannans are cell envelope components of Gram-positive bacteria that have been extensively associated with the pathogenesis of disease . In order to study such associations, purification of these macroamphiphiles is essential for resolving their structures and diverse biological effects . We describe herein a method for purification of lipoglycan components from Propionibacterium acnes . This method uses the existing phenol-water extraction, followed by hydrophobic interaction chromatography and an additional purification step that utilises preparative electrophoresis for the separation of two lipoglycan components . Analysis of these lipoglycans revealed evidence for a lipid anchor based on fatty acids whilst the polysaccharide moiety contained significant amounts of mannose, glucose and galactose, together with an amino sugar suspected of being a diaminohexuronic acid . These latter components have been previously identified as components of the P . acnes cell wall polysaccharide . Consequently, it is proposed that there may be a relationship between the structures of these distinctive cell envelope polymers.

J Med Dent Sci, 2003 Dec, 50(4), 265 - 74
Pulmonary granulomas caused experimentally in mice by a recombinant trigger-factor protein of Propionibacterium acnes; Minami J et al.; Etiology of sarcoidosis remains unknown . A trigger factor from Propionibacterium acnes causes a cellular immune response in some sarcoid patients but not in nonsarcoid subjects . We examined whether experimentally induced hypersensitivity to the trigger factor gives rise to granulomas . Female C57BL/6 mice primed intravenously with P . acnes or not were sensitized with recombinant-protein RP35, a fragment of P . acnes trigger factor, and complete Freund's adjuvant . In controls, RP35 was replaced with P . acnes or one of two control proteins . In primed and unprimed mice, pulmonary granulomas were found in some of the mice sensitized with RP35 or P . acnes but in no control-protein-sensitized mice . Detection of pulmonary granulomas (25-57%) did not differ significantly between mice sensitized with RP35 or P . acnes, primed or not . No difference in popliteal lymph-node-cell reactivity and serum antibodies to these two antigens was found between mice with and without pulmonary granulomas . P . acnes was cultured from the lungs of 8 (33%) of 24 untreated mice . The recombinant trigger-factor protein of P . acnes caused pulmonary granulomas in primed and unprimed mice sensitized with the protein and adjuvant . Sarcoid granulomas may form during hypersensitivity to antigens of P . acnes indigenous to the affected organ.

Shanghai Kou Qiang Yi Xue, 1998 Sep, 7(3), 143 - 6
{A bacteriology analysis from infected root canals of human deciduous teeth}; Hu YW et al.; OBJECTIVE: To provide a basis for therapy and prevention, the flora of infected root canals of human deciduous teeth was analyzed.METHODS: By immediate-enzyme method, the bacteria compositions of 22 cases with infected root canals of deciduous teeth, including 8 cases with acute periapical inflammation and 14 with chronic ones, were examined . RESULTS: Among 240 strains bactera, 200 strains were obligate anaerobes, belonging to the genera peptostreptococcus, bacteriodes, veillonella, eubacterrum, propionibacterium, actinomyces and fusobacterium . Bacteriodes and eusobacterium especially B . gingivalis and F . nucleatum have been more frequently isolated from root canals with acute periapical inflammation than that with chronic ones (P<0.05) . In chronic cases, veillonella especially V . parvula, were more frequently isolated than acute inflammation . CONCLUSION: Periaplcal inflammation of deciduous teeth was mixed polymicrobial infections regardless of acute or chronic cases and anaerobic bacteria were dominated . B . gingivalis and F . nucleatum probably were related to acute periapical inflammation of deciduous teeth . The effect of V . parvula on chronic periapical innammation of deciduous teeth should not be neglected.

Appl Environ Microbiol, 2004 Apr, 70(4), 2240 - 4
Prevalence of the genes encoding propionicin T1 and protease-activated antimicrobial peptide and their expression in classical propionibacteria; Faye T et al.; The purpose of this study was to investigate the frequency of production of the bacteriocin propionicin T1 and the protease-activated antimicrobial peptide (PAMP) and their corresponding genes in 64 isolates of classical propionibacteria . This study revealed that these genes are widespread in Propionibacterium jensenii and Propionibacterium thoenii but absent from the remaining species of classical propionibacteria that were studied . The pro-PAMP-encoding gene (pamA) was found in 63% of the P . jensenii strains and 61% of the P . thoenii strains, and all of these strains displayed PAMP activity . The propionicin T1-encoding gene (pctA) was present in 89% of the P . thoenii strains and 54% of the P . jensenii strains . All P . thoenii strains containing the pctA gene exhibited antimicrobial activity corresponding to propionicin T1 activity, whereas only 38% of the pctA-containing P . jensenii strains displayed this activity . Sequencing of the pctA genes revealed the existence of two allelic variants that differed in a single nucleotide in six strains of P . jensenii; in these strains the glycine at position 55 of propionicin T1 was replaced by an aspartate residue (A variant) . No strains harboring the A variant showed any antimicrobial activity against propionicin T1-sensitive bacteria . An open reading frame (orf2) located immediately downstream from the pctA gene was absent in three strains containing the G variant of propionicin T1 . Two of these strains showed low antimicrobial activity, while the third strain showed no antimicrobial activity at all . The protein encoded by orf2 showed strong homology to ABC transporters, and it has been proposed previously that this protein is involved in the producer immunity against propionicin T1 . The limited antimicrobial activity exhibited by the strains lacking orf2 further suggests that this putative ABC transporter plays an important role in propionicin T1 activity.

FEBS Lett, 2004 Mar 26, 562(1-3), 22 - 6
A thermostable manganese-containing superoxide dismutase from pathogen Chlamydia pneumoniae; Yu J et al.; The gene CP0718 encoding a putative manganese-containing superoxide dismutase of Chlamydia pneumoniae AR39 was cloned and expressed in Escherichia coli . Characterization showed that the expressed protein with a monomeric molecular mass of 23.1 kDa had superoxide dismutase (SOD) activity and the cofactor of CpSOD was a bivalent manganese cation . It is unexpected that this enzyme was hyperthermostable, and maintained about 90% activity after incubation at 70 degrees C for 60 min . Manganese binding residues found in the SOD sequences from different species are conserved in CpSOD . Bioinformatics analysis compared with Propionibacterium shermanii MnSOD was performed to elucidate the CpSOD hyperthermostability based on amino acid sequences.

Br J Dermatol, 2004 Mar, 150(3), 421 - 8
Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P . acnes GroEL; Graham GM et al.; BACKGROUND: Keratinocytes form the first line of defence in the skin and alert the host to danger by the production of a number of cytokines and chemokines . However, the interaction of commensal microorganisms with keratinocytes has not been well studied . OBJECTIVES: To investigate the effect of viable and nonviable cells of Propionibacterium acnes in both exponential and stationary growth phases, and of P . acnes GroEL on cytokine production by human primary keratinocytes . METHODS: Actively proliferating or contact-inhibited keratinocytes were cocultured with viable or formaldehyde-killed P . acnes cells in either the exponential or stationary phase of growth . Culture supernatants were assayed by enzyme-linked immunosorbent assay for the cytokines interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and granulocyte/macrophage colony-stimulating factor (GM-CSF) . Keratinocytes were also stimulated with different concentrations of P . acnes GroEL and supernatants assayed for cytokines . RESULTS: Viable P . acnes in the stationary phase of growth stimulated keratinocyte monolayers to produce significantly higher amounts of IL-1alpha, TNF-alpha and GM-CSF than unstimulated keratinocytes . Viable exponential-phase bacteria stimulated production of significantly higher amounts of TNF-alpha and GM-CSF but these levels were significantly lower than those for stimulation with stationary-phase bacteria . Nonviable P . acnes from either growth phase was not able to stimulate cytokine production . P . acnes GroEL at concentrations in the range 0.05-1.0 micro g mL(-1) was able to induce increased production of cytokines by keratinocytes in a dose-dependent manner . This was analogous to stimulation with Escherichia coli GroEL . CONCLUSIONS: Stimulation of cytokine production by P . acnes and P . acnes GroEL may be important in the pathogenesis of inflammatory acne vulgaris and may have wider implications for the immunomodulation of the human immune system by commensal skin microorganisms.

J Agric Food Chem, 2004 Mar 24, 52(6), 1749 - 52
Enrichment of conjugated linoleic acid in oats (Avena sativa L.) by microbial isomerization; Vahvaselka M et al.; A method for microbial isomerization of oat linoleic acid to conjugated linoleic acid (CLA) was developed . The method includes hydrolysis of oat lipids in aqueous flour slurries by the endogenous oat lipase . Then, the flour slurry containing free linoleic acid is utilized as a substrate for the isomerization reaction carried out by resting cells of Propionibacterium freudenreichii ssp . shermanii . The isomerization reaction progressed most effectively when, after the lipid hydrolysis period, the pH of the slightly acidic oat slurry was elevated to 8.0-8.5 and maintained at this range . With slurries containing 5% (w/v) oat flour, the amounts of CLA formed per dry matter were up to 10.1 mg/g corresponding to 102 mg/g lipids or 0.44 mg/mL slurry . Increments in the flour content up to 15% increased the volumetric production of CLA to 0.85 mg/mL . The proportion of the cis-9,trans-11 isomer was 80% of the total CLA formed . CLA could be concentrated into the solid material of the oat slurry by acidification.

Eur J Clin Microbiol Infect Dis, 2004 Apr, 23(4), 310 - 6 Epub 2004 Mar 13.
Risk factors for mortality in patients with anaerobic bacteremia; Wilson JR et al.; Risk factors for mortality in anaerobic bacteremia have been incompletely defined . The aims of the present study were to determine clinical significance by pathogen for a broad range of obligate anaerobic organisms isolated from blood, and to define the factors independently associated with mortality among those with clinically significant bacteremia . All patients who had anaerobic bacteria isolated from blood over a 19-month period (from 1 September 1998 to 1 April 2000) at two urban teaching hospitals were included in this study . Each case was analyzed for clinical significance by means of a retrospective medical record review using predetermined definitions . Information was collected on a broad range of clinical and microbiological factors, which were evaluated for their association with mortality using a Cox proportional hazards model . Among 166 patients with obligate anaerobic bacteria isolated from blood, 73 (44%) were deemed to have clinically significant bacteremia . Clinical significance ranged from 0% (0/53) for Propionibacterium spp . to 96% (43/45) for Bacteroides spp . The crude mortality rate in patients with clinically significant anaerobic bacteremia was 25% (18/73) . Mortality was significantly associated with age, polymicrobial infection, and underlying heart, kidney or liver disease in univariate analysis . Only the presence of liver disease (relative risk, 5.3; 95% confidence interval, 1.7-16.0; P=0.003) and patient age (relative risk, 1.06/y; 95% confidence interval, 1.0-1.1; P=0.005) remained significant in multivariate analysis . Among patients with anaerobic bacteremia, clinical significance varies markedly by pathogen and mortality is independently associated with age and underlying liver disease.

Phytother Res, 2004 Feb, 18(2), 180 - 3
Antibacterial activity of ent-kaurene diterpenoids from Rabdosia rosthornii; Kubo I et al.; Biological activities of ent-kaurene diterpenoids, rosthornins A-D, isolated from the ether extract of the dried leaves of Rabdosia rosthornii (Diels) Hara (Labiatae) were tested . They exhibited antibacterial activity specifically against Gram-positive bacteria, among which Propionibacterium acnes was noted to be the most susceptible .

Drugs Exp Clin Res, 2003, 29(4), 157 - 9
Propionibacterium acnes lipase in seborrheic dermatitis and other skin diseases and Unsei-in; Higaki S et al.; We examined Propionibacterium acnes lipase in skin diseases and Unsei-in . Butyric acid production in axillary seborrheic dermatitis (ASD) was higher than in other dermatitis, and that in acne vulgaris (AV) was significantly higher than in controls . P . acnes lipase is the pathogenic factor in AV and fatty acids produced by lipase might be the pathogenic factor in ASD . Unsei-in suppressed P . acnes lipase probably because some ingredients have antimicrobial and anti-inflammatory activities.

Z Naturforsch {C}, 2004 Jan-Feb, 59(1-2), 93 - 8
In situ assessment of porphyrin photosensitizers in Propionibacterium acnes; Ramberg K et al.; Porphyrins are known to be efficient photosensitizer molecules and the combined action of light and porphyrins in Propionibacterium acnes have a lethal action on the cells . Identification and quantification of in situ porphyrins in P . acnes have been done using an integrating sphere connected to an ordinary absorption spectrophotometer, and the amounts of porphyrins in the cells were quantified by measuring scattering free absorption spectra of the cell suspensions . The concentration of porphyrins in P . acnes cells were increased in either of two ways; by the addition of delta-aminolevulinic acid (ALA), which lead to the formation of coproporphyrin III under the incubation conditions used in these experiments, or by the addition of protoporphyrin IX (PPIX) to the cell suspension . In the latter case, PPIX molecules are taken up by the cells in a membrane-mediated uptake mechanism, and accumulate in the cells either on a monomeric or a particular aggregate form . The fraction of porphyrins on aggregate form increased with increasing PPIX additions . In the case of ALA induced porphyrin production, only monomeric porphyrins were stored in the cells . In both cases, the cells have a limited binding capacity of monomeric porphyrins, which is estimated to be 3 x 10(5) molecules/cell, or one porphyrin molecule to every 100st lipid molecule in the cell membrane.

Int J Food Microbiol, 2004 Mar 1, 91(2), 195 - 204
Enhancement of trehalose production in dairy propionibacteria through manipulation of environmental conditions; Cardoso FS et al.; We have shown that the ability to produce trehalose is widespread within the genus Propionibacterium . Eighteen strains isolated from dairy sources were screened for trehalose synthesis; the effect of environmental conditions on trehalose production was evaluated in Propionibacterium freudenreichii ssp . shermanii NIZO B365, a strain that accumulated high amounts of this disaccharide . Lactose was the best carbohydrate source for trehalose production, whereas lactate, the substrate that led to the highest specific growth rate, was a poor precursor . Trehalose was consumed after exhaustion of the carbon source in the medium, suggesting its role as a reserve compound . The production of trehalose was not affected by lowering the growth temperature from 30 to 20 degrees C . On the other hand, the maximum trehalose accumulation increased from about 200 to 400 mg of trehalose/g of cell protein upon decreasing the pH from 7.0 to 4.7, by increasing the concentration of NaCl to 2% (w/v), or during growth under aerobic conditions (50% air saturation, 24 microM O(2), pH 7.0) . In the absence of NaCl, trehalose accumulated concomitantly with growth, but an increase in salinity triggered a high trehalose production already in the early exponential growth phase . The data provide evidence for a dual function of trehalose as a reserve compound and as a stress-response metabolite . Moreover, P . freudenreichii ssp . shermanii NIZO B365 was able to produce high levels of trehalose in skim milk, which is promising for the implementation of fermented dairy products.

Acta Crystallogr D Biol Crystallogr, 2004 Mar, 60(Pt 3), 521 - 3 Epub 2004 Feb 25.
Expression and crystallization of several forms of the Propionibacterium shermanii transcarboxylase 5S subunit; Hall PR et al.; The dimeric outer 5S subunit of transcarboxylase has been expressed in three different forms and crystallized: native 5S, 5S-His(6) and selenomethione-5S-His(6) . All the crystals have an orthorhombic space group, but while native 5S forms primitive orthorhombic crystals, 5S-His(6) crystals are either C-centered or primitive and SeMet-5S-His(6) crystals are C-centered . Crystallization of native 5S requires the addition of lithium sulfate, whereas this salt prevented crystallization of 5S-His(6) . All 5S crystals diffract to approximately 2.0 A resolution with synchrotron radiation . Efforts are under way to solve the structure of SeMet-5S-His(6) using MAD.

Arch Dermatol, 2004 Feb, 140(2), 210 - 4
Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis; Westerhof W et al.; BACKGROUND: Progressive macular hypomelanosis is a common hypopigmentation mainly on the central parts of the trunk, predominantly in young adults, especially women . It is often mistaken for pityriasis versicolor and pityriasis alba . It occurs in all races and has been described in many parts of the world . We discovered follicular red fluorescence restricted to lesional skin . We suspected a relation with a porphyrin-producing bacteria residing in sebum of the pilosebaceous duct, and we therefore performed a study in 8 patients.Observation In all biopsy specimens taken from lesional skin of 8 women, we could demonstrate gram-positive bacteria in the pilosebaceous duct, and a mild perifollicular lymphocytic infiltrate was seen . In all but 1 patient, Propionibacterium acnes was yielded from cultured biopsy specimens taken from follicular lesional skin . Healthy follicular skin did not show bacteria in histological sections, and cultures did not yield anaerobic bacteria . CONCLUSIONS: There seems to be a relation between the presence of P acnes and the hypopigmented macules . We propose that a factor is produced by these strains of P acnes, which interfere with melanogenesis . Based on these observations, we are undertaking a clinical trial to find a treatment for this troubling, intractable disease.

Int Endod J, 2004 Jan, 37(1), 61 - 9
Resolution of persistent periapical infection by endodontic surgery; Ferreira FB et al.; AIM: To examine the surfaces of a root tip removed during surgical endodontic treatment for the presence of microorganisms . SUMMARY: The present clinical case illustrates an endodontic retreatment of a maxillary premolar tooth with a fistula and periapical reaction . The case was under treatment for 1 year, during which an intracanal medicament was replaced several times . As the lesion did not decrease and exudate was persistent through the fistula and root canal, root end resection with root end filling was performed . Microbiological samples were collected from the fistula, where Propionibacterium acnes, a species associated with endodontic failures, was detected by appropriate anaerobic technique . The resected root apex was observed by scanning electron microscopy (SEM), which revealed cocci and fungal forms surrounding one of the foramina . After 12 months, the periapical lesion had reduced.

J Natl Cancer Inst, 2004 Feb 4, 96(3), 201 - 9
Mobilization of dendritic cell precursors into the circulation by administration of MIP-1alpha in mice; Zhang Y et al.; BACKGROUND: Dendritic cells (DCs) play a central role in immune responses and may be useful adjuvants for tumor vaccine therapy . We previously reported that F4/80(-)B220(-)CD11c(+) DC precursors expressing the CC chemokine receptors CCR1 and CCR5 are mobilized rapidly into the circulation in mice injected with Propionibacterium acnes and are recruited into inflammatory tissue by macrophage inflammatory protein 1alpha (MIP-1alpha), which binds to CCR1 and CCR5 . Here we investigate the mechanisms of DC precursor mobilization and the antitumor effect of these cells in mice . METHODS: Numbers of DC precursors in peripheral blood were determined in P . acnes-treated mice (groups of 10 C57BL/B6 {B6} wild-type mice, CCR1(-/-) mice, CCR5(-/-) mice, and B6 mice treated with antibody to MIP-1alpha or control antibody) and in B6 mice injected with recombinant MIP-1alpha . MIP-1alpha-mobilized DC precursors matured by treatment with granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor-alpha and pulsed with B16 melanoma lysates were assayed for their ability to confer protective immunity against tumor challenge in vivo and to induce cytotoxic T lymphocytes against B16 tumor cells in vitro . RESULTS: The recruitment of DC precursors into the circulation by P . acnes administration was higher in B6 mice (12.6%, 95% confidence interval {CI} = 9.1% to 16.1%) than in CCR1(-/-) (9.0%, 95% CI = 7.5% to 10.5%), CCR5(-/-) (6.3%, 95% CI = 5.2% to 7.3%), or anti-MIP-1alpha antibody-treated (6.6%, 95% CI = 5.7% to 7.5%) mice . Injection of MIP-1alpha also mobilized DC precursors into the circulation (13.1%, 95% CI = 10.8% to 15.6%) . Matured MIP-1alpha-mobilized-DC precursors pulsed with B16 tumor lysates elicited B16-specific antitumor immunity in vitro and in vivo . CONCLUSIONS: MIP-1alpha and its receptors are important in recruiting DC precursors into the circulation . DC precursors mobilized rapidly by MIP-1alpha may provide sufficient useful DC precursors for DC-based vaccination in cancer treatment.

Arch Microbiol, 2004 Mar, 181(3), 215 - 30 Epub 2004 Jan 17.
Mass spectrometry proteomic analysis of stress adaptation reveals both common and distinct response pathways in Propionibacterium freudenreichii; Leverrier P et al.; Microorganisms used in food technology and probiotics are exposed to technological and digestive stresses, respectively . Traditionally used as Swiss-type cheese starters, propionibacteria also constitute promising human probiotics . Stress tolerance and cross-protection in Propionibacterium freudenreichii were thus examined after exposure to heat, acid, or bile salts stresses . Adapted cells demonstrated acquired homologous tolerance . Cross-protection between bile salts and heat adaptation was demonstrated . By contrast, bile salts pretreatment sensitized cells to acid challenge and vice versa . Surprisingly, heat and acid responses did not present significant cross-protection in P . freudenreichii . During adaptations, important changes in cellular protein synthesis were observed using two-dimensional electrophoresis . While global protein synthesis decreased, several proteins were overexpressed during stress adaptations . Thirty-four proteins were induced by acid pretreatment, 34 by bile salts pretreatment, and 26 by heat pretreatment . Six proteins are common to all stresses and represent general stress-response components . Among these polypeptides, general stress chaperones, and proteins involved in energetic metabolism, oxidative stress response, or SOS response were identified . These results bring new insight into the tolerance of P . freudenreichii to heat, acid, and bile salts, and should be taken into consideration in the development of probiotic preparations.

Microb Pathog, 2004 Mar, 36(3), 171 - 4
Studies on the cytotoxic effects of Propionibacterium acnes strains isolated from cornea; Csukas Z et al.; Eukaryotic tissue culture appears to be a suitable model for measuring the bacterial cytotoxic effect . Propionibacterium acnes strains were isolated from corneal tissue removed by keratoplastic surgery from patients with corneal dystrophy or bullous keratopathy . The cytotoxic effect of the filtrates of 10 P . acnes strains were studied by means of measuring the decrease of the mitochondrial dehydrogenase activities of viable epithelial (HeLa) and fibroblastic (BHK-21) cell cultures . A time and concentration dependent, reversible cytotoxic effect was detected in both tissue types . The results also showed that strains of P . acnes are capable of surviving anaerobic conditions for as long as 8 months and suggest that production cytotoxic effects during the long persistence it may harm human tissue.

J Vasc Surg, 2003 Dec, 38(6), 1384 - 9
Multiple bacteria in aortic aneurysms; Marques da Silva R et al.; OBJECTIVE: The purpose of the present study was to reexamine the possibility that bacteria, particularly anaerobes, are present in aortic aneurysms . METHODS: From December 2000 to November 2001, 53 samples from aneurysm walls were collected from 49 patients during reconstructive surgery . The tissue specimens were sectioned and cultured under anaerobic conditions . Twenty-eight specimens were also subjected to scanning or transmission electron microscopy . RESULTS: Anaerobic cultivation yielded bacteria in 14 of the 53 samples (26.4%) . All bacteria were gram-positive cocci or rods from nine genera and 12 species . Five cultures (35%) were mixed, containing two bacterial species . Mixed aerobic and anaerobic species were found in four samples (28.5%) . Anaerobic bacteria were recovered from 10 of 14 positive cultures (71%) . Among anaerobes found were Propionibacterium acnes, Propionibacterium granulosum, Actinomyces viscosus, Actinomyces naeslundii, and Eggerthella lenta . Coaggregating bacteria of different sizes and structure were found on the aneurysm walls and inside the intravascular plaque at electron microscopy . Bacteria were found in 20 of the 28 samples (71%) examined with scanning or transmission electron microscopy . CONCLUSION: Multiple bacteria, many of which did not belong to the indigenous skin microflora, colonize aortic aneurysms . It is not clear whether the bacteria contribute to weakening of the aortic wall by eliciting inflammation or whether they are secondary colonizers of aneurysms.

Skinmed, 2003 Jul-Aug, 2(4), 234 - 45
Subantimicrobial dose doxycycline for acne and rosacea; Bikowski JB; Acne vulgaris and rosacea present therapeutic challenges due to their chronicity, potential for disfigurement, and psychosocial impact . Although pathophysiologically distinct, both conditions have major inflammatory components . Consequently, topical and systemic antimicrobial agents are routinely prescribed for extended periods . Emergence of resistant strains of Propionibacterium acnes, adverse events, and compliance issues associated with chronic systemic tetracycline use have led to new treatment approaches . At subantimicrobial doses, tetracyclines reduce inflammation via anticollagenolytic, antimatrix-degrading metalloproteinase, and cytokine down-regulating properties . Subantimicrobial dose (SD) doxycycline (Periostat 20 mg) has clinical utility in periodontitis and has been investigated in a double-blind, placebo-controlled trial in the treatment of moderate facial acne as well as in an open label study in the treatment of rosacea . The results of subantimicrobial dose doxycycline treatment in early trials support its benefits and further investigation in acne and rosacea.

Dermatology, 2003, 207(4), 343 - 8
Is androgenetic alopecia a photoaggravated dermatosis?
Trueb RM.
Progressive thinning of the scalp hair in androgenetic alopecia (AGA) results in a gradual decline in natural protection of the scalp from ultraviolet radiation (UVR) . A number of pathologic conditions of the scalp are evidently related to UVR, particularly photosensitive diseases and disorders of the chronically photodamaged bald scalp . The most important chronic effects of UVR are photocarcinogenesis and solar elastosis . Besides these, erosive pustular dermatosis and 'red scalp' are distinct disorders peculiar to the balding scalp . While the consequences of sustained UVR on the unprotected scalp are well appreciated, the effects of UVR on hair loss have widely been ignored . However, clinical observations and theoretical considerations suggest that UVR may have negative effects: acute telogen effluvium from UVR has been described, and the production of porphyrins by Propionibacterium sp . in the pilosebaceous duct, with photoactivation of porphyrins leading to oxidative tissue injury, has been implicated in follicular microinflammation . Alternatively, keratinocytes themselves may respond to physicochemical stress from UVR, besides irritants and pollutants, by producing radical oxygen species and nitric oxide and by releasing proinflammatory cytokines, eventually leading to injury of the putative site of follicular stem cells in the superficial portion of the hair follicle . Since all of these processes involved in hair loss share the common feature that they are induced or exacerbated by exposure to sunlight, it is proposed that AGA is a photoaggravated dermatosis that requires photoprotection .

Am J Clin Dermatol, 2003, 4(12), 813 - 31
Is antibiotic resistance in cutaneous propionibacteria clinically relevant? : implications of resistance for acne patients and prescribers; Eady AE et al.; It is well recognized that some patients with acne do not respond adequately to antibiotic therapy . It is important to distinguish antibiotic recalcitrant acne which we would suggest represents acne that shows a diminished response to treatment irrespective of the cause as opposed to 'antibiotic-resistant acne' which is acne that is less responsive to treatment as a direct consequence of skin colonization with resistant propionibacteria . Here we show that antibiotic-resistant acne is not just a theoretical possibility but a real phenomenon that could have important consequences for patients and prescribers . The relationship between skin colonization by antibiotic-resistant propionibacteria and treatment outcomes is a complex one that is explained at the follicular level by physiological differences affecting local drug concentrations . A systematic review of the literature on antibiotic-resistant propionibacteria revealed methodological shortcomings in studies of their prevalence and a paucity of evidence on their clinical significance . Despite the elucidation of resistance mechanisms in cutaneous propionibacteria, our continuing inability to distinguish between strains of Propionibacterium acnes means that we still do not fully understand how resistance spreads, although person-to-person transfer is most likely . Finally, we present a decision tree for acne management in an era of prudent antimicrobial prescribing that provides an alternative to existing treatment algorithms by placing topical retinoids and not antibiotics at the cornerstone of acne management.

Surgery, 2003 Nov, 134(5), 818 - 26
Effects of OPC-6535 on lipopolysaccharide-induced acute liver injury in the rat: involvement of superoxide and tumor necrosis factor-alpha from hepatic macrophages; Hasegawa T et al.; BACKGROUND: The objective of this study was to investigate the effects of OPC-6535 on Propionibacterium acnes-primed and lipopolysaccharide-induced liver injury in the rat . METHODS: P . acnes was administered intravenously to the rat at 16 mg/kg 7 days before the experiments . In liver perfusion experiments, lipopolysaccharide was mixed in perfusion buffer at 2.5 microg/mL . The chemiluminescence method and histochemical reduction of nitro blue tetrazolium were used for detecting superoxide . Release of cytokines into the perfusate was examined . In in vivo experiments, lipopolysaccharide was administered intravenously to the rat at 200 microg/kg . Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and cytokines were determined in the plasma, and myeloperoxidase activity was measured in the liver tissue . OPC-6535 was given intravenously at 1 mg/kg 30 minutes before lipopolysaccharide challenge, and was then, in perfusion experiments, added to the buffer at 10 micromol/L . RESULTS: In perfusion experiments, P . acnes and lipopolysaccharide caused dramatic production of superoxide, tumor necrosis factor-alpha (TNF-alpha) and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) . Superoxide was mainly from hepatic macrophages . Treatment with OPC-6535 suppressed superoxide and TNF-alpha but did not affect GRO/CINC-1 . In in vivo experiments, P . acnes and lipopolysaccharide increased the level of TNF-alpha, GRO/CINC-1, AST and ALT in the plasma, and myeloperoxidase activity in the liver . OPC-6535 reduced TNF-alpha, AST, and ALT, but did not affect GRO/CINC-1 or myeloperoxidase . CONCLUSION: Attenuation of liver injury by OPC-6535 is believed to be due to its inhibitory effects on superoxide and TNF-alpha production by hepatic macrophages in P . acnes- and lipopolysaccharide-treated rats.

Sarcoidosis Vasc Diffuse Lung Dis, 2003 Oct, 20(3), 197 - 203
Propionibacterium acnes DNA detected in bronchoalveolar lavage cells from patients with sarcoidosis; Hiramatsu J et al.; BACKGROUND AND AIM OF THE WORK: The causes of sarcoidosis are unknown . Propionibacterium acnes is so far the only bacterium to be found in sarcoid lymph nodes . We attempted to detect P . acnes DNA in cells recovered by bronchoalveolar lavage (BAL) from patients with sarcoidosis . METHODS: BAL cells from 30 patients with histologically proven sarcoidosis and 30 controls with other lung diseases were examined by a nested polymerase chain reaction (PCR) for 16S rRNA of P . acnes . BAL cells from three recent sarcoid patients and two control patients were also examined by in situ PCR to locate P . acnes DNA . Clinical findings in sarcoid patients with and without positive results by PCR were compared . RESULTS: P . acnes DNA was detected in BAL cells from 21 (70%) sarcoid patients and 7 (23%) control patients . In situ signals of P . acnes DNA were detected in the cytoplasm of 0.2% to 2.8% of alveolar macrophages from sarcoid patients, but from no cells of the control patients . Gallium-67 uptake by lung parenchyma was found in about half of the sarcoid patients with P . acnes DNA, but in none of the other sarcoid patients . More of these patients with such DNA had lung parenchymal shadows in chest X-ray films and were in more advanced stages of the disease than the other sarcoid patients . CONCLUSIONS: Detection of P . acnes DNA in BAL cells was significantly more common in the patients with confirmed sarcoidosis . Detection was associated with some indices of disease activity in the lung.

Clin Microbiol Infect, 2003 Nov, 9(11), 1125 - 7
Molecular diagnosis of a vascular prosthesis infection, due to Propionibacterium acnes, by amplification and sequencing of 16S rDNA; Le Page L et al.; We describe a case of indolent vascular prosthesis infection due to Propionibacterium acnes . The microorganism was identified only by amplification and sequencing of 16S rDNA, while standard cultures remained negative . This observation underscores the usefulness of molecular techniques for the diagnosis of infection caused by fastidious microorganisms.

FEMS Microbiol Lett, 2003 Nov 7, 228(1), 51 - 5
Analysis of clinical isolates of Propionibacterium acnes by optimised RAPD; Perry AL et al.; Random amplification of polymorphic DNA (RAPD) was evaluated as a genotypic method for typing clinical strains of Propionibacterium acnes . RAPD can suffer from problems of reproducibility if parameters are not standardised . In this study the reaction conditions were optimised by adjusting template DNA concentration and buffer constituents . All isolates were typeable using the optimised RAPD protocol which was found to be highly discriminatory (Simpson's diversity index, 0.98) and reproducible . Typing of P . acnes by optimised RAPD is an invaluable tool for the epidemiological investigation of P . acnes for which no other widely accepted method currently exists.

Eur J Pharm Biopharm, 2003 Nov, 56(3), 407 - 12
Hydrogel patches containing triclosan for acne treatment; Lee TW et al.; Adhesive hydrogel patches containing Triclosan (TS) were prepared as an anti-acne dosage form . Sodium polyacrylate and carboxymethylcellulose (sodium salt) were used as matrix polymers, and Al(3+), produced by the reaction of dihydroxy aluminum aminoacetate and L(+)-tartaric acid, was employed as a crosslinking agent for the negatively charged polymers . The crosslinking reactions were done at 25, 40 and 50 degrees C for predetermined time intervals . The semi-solid gels were obtained only when the reaction period was more than 12 h, but the polymer gels were fluidic with a shorter reaction . The swelling ratios increased as the reaction period was prolonged and the reaction temperature increased, indicating that the degree of the crosslinking is proportional to the reaction period and the temperature . On a scanning electron microphotograph, the crosslinked gel exhibited a honeycomb-like structure having pores of a few micrometers . The adhesive force of a patch, which could be easily attached to and peeled off facial skin, was 45.5 gmf and it increased by adding poly acrylic acid into the patch formulations . Propionibacterium acnes (ATCC 6919) growth inhibition area around the patch was not significant on an agar plate when TS content was 0.01 wt.%, but the antibacterial activity was apparent when the content was 0.05 wt.% . In vitro permeation revealed that up to 5 wt.% of Transcutol (TC) content in patch, TC, a permeation enhancer, significantly increased the amount of TS transported into hairless mouse skins but it did not substantially accelerate TS transportation into the receptors of Franz diffusion cells . Since our patches for the treatment of acne was aimed to localize TS into skins, TC content of 5 wt.% seems to be adequate for the dermal delivery of TS . The model patches in this study would be applicable to facial skins for the treatment of acne.

Vet Q, 2003 Sep, 25(3), 131 - 6
First cases of animal diseases published since 2000 . 3 . Cattle; Elsinghorst TA; In this third article of a series of papers listing first case reports of animal diseases published since 2000, the following seven cases of cattle diseases are discussed: AL amyloidosis . Canola oil intoxication . Disseminated intracytoplasmic neuronal vacuolation . Encephalomyelitis associated with Akabane virus infection in adult cows . Lower limb deformity: "mirror image duplication of the plantar/palmar half of the distal portion of the digit" . Lupinus argenteus intoxication . Novel Propionibacterium infection . After a short introduction, the bibliographical data, the abstract of the author(s), and some additional information derived from the article are given . The article will be regularly updated adding overlooked as well as new first reports.

Eur Radiol, 2003 Oct, 13(10), 2304 - 8 Epub 2003 Mar 13.
Diagnostic management of patients with SAPHO syndrome: use of MR imaging to guide bone biopsy at CT for microbiological and histological work-up; Kirchhoff T et al.; Propionibacterium acnes (P . acnes) is suspected to be involved in the pathophysiology of SAPHO syndrome, since it has been isolated repeatedly through open surgical bone biopsy . This study demonstrates the role of MRI in identifying inflamed bone areas in patients with SAPHO syndrome and the role of CT-guided bone biopsies in obtaining samples from these areas for microbiological and histopathological investigations, thus obviating open surgery . Fourteen consecutive patients with SAPHO syndrome were investigated by MRI to identify acute inflammatory changes in hyperostotic periarticular bone . The CT-guided biopsies for microbiological investigations were taken from the areas identified . Patients positive for P . acnes were started on long-term antibiotic therapy according to antibiotic susceptibility . On MRI the inflammatory changes appeared as hyperintense areas on fat-saturated T2 fast-spin-echo (FSE) images and showed signal increase on fat-saturated T1 SE images after Gd-DTPA . With MR localization CT-guided bone biopsies yielded P . acnes in 8 patients . No bacteria could be isolated from the remaining 6 patients . Acute inflammatory bone changes in SAPHO syndrome are well localized by MRI . With MR localization, CT-guided bone biopsies offer a minimally invasive alternative to open surgery in the detection of . P . acnes leading to the institution of a specific antibiotic therapy.

Biol Pharm Bull, 2003 Oct, 26(10), 1393 - 7
Influence of histamine in a liver injury model induced by Propionibacterium acnes and lipopolysaccharide; Kurihara H et al.; In normal mice, plasma histamine levels were 29.4+/-10.1 pmol/ml . When 0.1 microg of lipopolysaccharide (LPS) was intravenously injected into Propionibacterium acnes (P . acnes)-primed ICR mice, histamine levels increased remarkably to 61.2+/-15.9 pmol/ml (p<0.001) . An increase was also observed in liver tissues . Oral administration of histidine at 200 mg/kg once daily for 5 d before intravenous LPS injection increased the plasma alanine aminotransferase (ALT) activity to 2936.5+/-356.3 IU/l, a significant change compared with the controls (2244.8+/-425.5 IU/l, p<0.05) . The 24 h survival rate after LPS injection was 72.7% in the mice treated with 50 mg/kg of ranitidine, in contrast with 50% in the control group although the treatment did not significantly decrease the plasma ALT activity . On the other hand, 50 mg/kg of pyrilamine significantly reduced plasma ALT activity (p<0.001) . The results suggested that histamine levels are related to hepatic damage in the P . acnes plus LPS induction of liver injury.

Dermatol Nurs, 2003 Aug, 15(4), 359 - 62
Antibiotic resistance of Propionibacterium acnes in acne vulgaris; Swanson JK; Acne vulgaris is a common skin disease affecting all ages . Antibiotics remain the most common prescribed agent for the treatment of acne . Improper use of antibiotics in the dermatological setting needs to be evaluated to prevent the increasing prevalence of antibiotic resistance.

J Leukoc Biol, 2003 Dec, 74(6), 1056 - 63 Epub 2003 Nov 21.
TNF revisited: TNF-independent antitumor activity in sera of mice sensitized with Propionibacterium acnes and challenged with lipopolysaccharide; Schwamberger G et al.; Sera of mice sensitized with bacteria and subsequently challenged with lipopolysaccharide promote hemorrhagic necrosis of tumors in vivo and display cytotoxic activity against tumor cells in vitro, which has been attributed to the induction of tumor necrosis factor (TNF) . Here, we describe the induction of a previously unrecognized antitumor activity in such sera, which is distinct from TNF but displays tumor-specific cytocidal activity in vitro as well as potent tumor-regressing activity in vivo . Biochemical analysis of this activity yielded a molecular mass of approximately 150 kDa, closely resembling a novel tumoricidal factor of murine macrophages (Mphi) termed MTC 170 (Mphi tumor cytotoxin, approximate molecular mass 170 kDa), which we have previously proposed to constitute a major effector pathway for the destruction of tumor cells by activated Mphi.

J Leukoc Biol, 2003 Nov, 74(5), 889 - 96 Epub 2003 Aug 11.
Generation and characterization of mice transgenic for human IL-18-binding protein isoform a; Fantuzzi G et al.; Interleukin (IL)-18 binding protein (IL-18BP) is a natural inhibitor of the pleiotropic cytokine IL-18 . To study the role of IL-18BP in modulating inflammatory responses in vivo, mice transgenic for human IL-18BP isoform a (IL-18BP-Tg) were generated . The transgene was expressed at high levels in each organ examined . High levels of bioactive human IL-18BPa were detectable in the circulation of IL-18BP-Tg mice, which were viable, fertile, and had no tissue or organ abnormality . The high levels of IL-18BP in the transgenic mice were able to completely neutralize the interferon-gamma (IFN-gamma)-inducing activity of exogenously administered IL-18 . Following administration of endotoxin, with or without prior sensitization with heat-inactivated Propionibacterium acnes, IL-18BP-Tg mice produced significantly lower serum levels of IFN-gamma and macrophage-inflammatory protein-2 compared with nontransgenic littermates . Significantly reduced production of IFN-gamma in response to endotoxin was also observed in cultures of IL-18BP-Tg splenocytes . Finally, IL-18BP-Tg mice were completely protected in a model of hepatotoxicity induced by administration of concanavalin A . These results indicate that high endogenous levels of IL-18BP in trangenic mice effectively neutralize IL-18 and are protective in response to different inflammatory stimuli.

Pneumonol Alergol Pol, 2003, 71(1-2), 51 - 8
{Evaluation of anaerobic flora in lung neoplasms}; Zajac-Lenczewska I et al.; Purpose of this study was to analyse the kind and frequency of anaerobic bacteria in the lower respiratory tract as well as susceptibility of the bacteria to antibiotics . Material from 35 patients with lung tumour derived from tumour and post-tumoural area sample . Collected sample was cultivated in anaerobic and aerobic conditions . Anaerobic bacteria were found in 23 (66%) samples . Totally there were 44 isolated of anaerobic bacteria strains . The most common G-negative strains belonged to genus of Bacteroides (11 strains); two types dominated: Bacteroides gracilis (4 strains) Bacteroides fragilis (4 strains) . Among G-positive anaerobic bacteria most common were Peptostreptococcus (9 strains) . G-positive rods were represented by Propionibacterium genus (8 strains) . The susceptibility of anaerobic bacteria was estimated towards mostly used antibacterial drugs . Results suggest that most of bacteria were susceptible for imipenem, piperacillin/tazobactam, amoxicillin/clavulanate, ampicillin/sulbactam, metronidazole, piperacillin and clindamycin . Bacteria were less susceptible to roxitromycin and examined cephalosporins . Most of the strains were resistant for cefuroxime.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2003 Aug, 96(2), 215 - 22
Polymerase chain reaction detection of Propionibacterium propionicus and Actinomyces radicidentis in primary and persistent endodontic infections; Siqueira JF Jr et al.; OBJECTIVE: Propionibacterium propionicus and the recently described species Actinomyces radicidentis have been isolated from infections of endodontic origin; nevertheless, the possibility exists that their actual prevalence may have been underestimated by culture . The purpose of our study was to assess the occurrence of these 2 species in different types of endodontic infections by using the sensitive 16S rDNA-based nested polymerase chain reaction approach . STUDY DESIGN: To detect these 2 species, nested polymerase chain reaction was performed directly in samples taken from primary endodontic infections associated with asymptomatic periradicular lesions, acute apical periodontitis, or acute periradicular abscesses and in samples from patients in whom endodontic therapy had failed . DNA was extracted from the samples and initially amplified by using universal 16S rDNA primers . In the second round of amplification, the first polymerase chain reaction products were used to detect a specific 16S rDNA fragment of either P propionicus or A radicidentis . RESULTS: P propionicus was detected in 6/21 (29%) root canal samples from teeth with chronic periradicular lesions, in 5/10 (50%) cases diagnosed as acute apical periodontitis, and in 7/19 (37%) pus samples aspirated from acute periradicular abscesses . Overall, this species was found in 18/50 (36%) samples taken from primary endodontic infections . Of the root canal samples obtained from root-filled teeth with chronic periradicular lesions, P propionicus was detected in 7/12 (58%) cases . A radicidentis was detected in 1/21 (5%) root canal samples from teeth with chronic periradicular lesions and in 1/10 (10%) cases of acute apical periodontitis . No pus sample yielded this species . In general, A radicidentis was detected in 2/50 (4%) samples taken from primary endodontic infections and in 1/12 (8%) root canal samples taken from patients in whom endodontic treatment had failed . CONCLUSIONS: P propionicus was found in a relatively large number of patients with primary and persistent endodontic infections . This strengthens the assumption that this bacterial species is an endodontic pathogen associated with different forms of periradicular diseases . In contrast, A radicidentis was only occasionally detected in the patients examined . The role played by this species in endodontic infections remains to be clarified.

Acta Derm Venereol, 2003, 83(4), 241 - 8
Pathological mechanisms of acne with special emphasis on Propionibacterium acnes and related therapy; Jappe U; Acne is a common disease that in cases of extreme disfiguration can have severe consequences for the personality development of young people and is associated with a relatively high prevalence of depression and suicide . Spontaneous regression is common, but acne can extend into the fourth and fifth decades of life . The pathogenesis is still not fully understood . Factors promoting the development of acne are: increased sebum production, ductal cornification, bacterial colonization of the pilosebaceus ducts and inflammation . However, there is evidence that inflammation is not a factor but rather a consequence of the interaction of the other three factors . Propionibacterium acnes releases pro-inflammatory cytokines as well as antigens and mitogen(s), with cellular and non-cellular responses to these products triggering inflammation . Treatment is often frustran . Therapeutical strategies are needed based on new understandings of the pathomechanisms involved in acne . The aim of this review is to summarize the data on aetiopathological factors in acne and their contribution to acne pathology and therapy.

J Ind Microbiol Biotechnol, 2003 Aug, 30(8), 500 - 9 Epub 2003 Jul 26.
Metabolic engineering of Escherichia coli for improved 6-deoxyerythronolide B production; Murli S et al.; Escherichia coli is an attractive candidate as a host for polyketide production and has been engineered to produce the erythromycin precursor polyketide 6-deoxyerythronolide B (6dEB) . In order to identify and optimize parameters that affect polyketide production in engineered E . coli, we first investigated the supply of the extender unit ( 2S)-methylmalonyl-CoA via three independent pathways . Expression of the Streptomyces coelicolor malonyl/methylmalonyl-CoA ligase ( matB) pathway in E . coli together with methylmalonate feeding resulted in the accumulation of intracellular methylmalonyl-CoA to as much as 90% of the acyl-CoA pool . Surprisingly, the methylmalonyl-CoA generated from the matB pathway was not converted into 6dEB . In strains expressing either the S . coelicolor propionyl-CoA carboxylase (PCC) pathway or the Propionibacteria shermanii methylmalonyl-CoA mutase/epimerase pathway, methylmalonyl-CoA accumulated up to 30% of the total acyl-CoA pools, and 6dEB was produced; titers were fivefold higher when strains contained the PCC pathway rather than the mutase pathway . When the PCC and mutase pathways were expressed simultaneously, the PCC pathway predominated, as indicated by greater flux of (13)C-propionate into 6dEB through the PCC pathway . To further optimize the E . coli production strain, we improved 6dEB titers by integrating the PCC and mutase pathways into the E . coli chromosome and by expressing the 6-deoxyerythronolide B synthase (DEBS) genes from a stable plasmid system.

Drugs, 2003, 63(15), 1579 - 96
Current concepts of the pathogenesis of acne: implications for drug treatment; Gollnick H; The pathogenesis of acne is complex, with strong evidence supporting the involvement of sebaceous hyperplasia, follicular hyperkeratinisation, bacterial hypercolonisation, as well as immune reactions and inflammation . High sebum concentrations and follicular hyperkeratinisation lead to a change of the follicular milieu with consecutive proliferation of bacteria, chiefly Propionibacterium acnes . This leads to further increased production of the pro-inflammatory cytokines interleukin-1alpha and tumour necrosis factor alpha by T cells and keratinocytes, leading to proliferation of both cell types . Follicular keratinocytes fail to differentiate by apoptosis and produce hypergranulosis similar to the impermeable skin outer layer, resulting in the formation of microcomedones . Further inflammatory responses lead to the development of increasing degrees of severity in inflammatory forms of acne.Retinoids aid the differentiation and reduce the hyperproliferation of keratinocytes, and can inhibit the migration of leucocytes . Combination therapy using retinoids plus benzoyl peroxide or antibacterials can treat existing acne lesions faster than the individual agents alone and can also prevent the development of new lesions . The new retinoids (e.g . adapalene) have not only the typical potent comedolytic activity but also anti-inflammatory effects . When added to antibacterial therapy, topical retinoids demonstrate faster and significantly greater reduction of inflammatory acne lesions and comedones than antibacterials alone.

Dev Immunol, 2002 Sep, 9(3), 143 - 9
Kupffer cell-mediated recruitment of dendritic cells to the liver crucial for a host defense; Matsuno K et al.; Tissue recruitment of dendritic cells (DCs) is essential for antigen presentation . When latex particulates were injected intravenously into rats, DC precursors were recruited to the liver . Propionibacterium acnes also induced the recruitment of definite mouse DC precursors . These DCs initially showed a selective binding to Kupffer cells . In the Kupffer cell-depleted rats, DCs could neither be recruited to the liver nor adhere to sinusoidal walls . Pretreatment with varied monosaccharides in vitro showed that sugar residues consisting of N-acetylgalactosamine were necessary for this binding . Mouse DC precursors had CC-chemokine receptor 1 and 5, while granulama tissues and rat Kupffer cells expressed the corresponding chemokine, macrophage inflammatory protein-lalpha . Recruited DC precursors phagocytosed latex or bacteria and some of them soon translocated to hepatic nodes and induced the immune response there . We conclude that after invasion of pathogens, Kupffer cells not only scavenge them but also recruit DCs/DC precursors via chemokine- and N-acetylgalactosamine-mediated interactions . The accelerated DC traffic and the presence of blood-lymph translocation would induce rapid and efficient immune responses and thus contribute to the local defense to antigens within liver tissues as well as systemic defense to blood-borne antigens.

Hepatology, 2003 Aug, 38(2), 335 - 44
Nuclear factor kappa B decoy oligodeoxynucleotides prevent endotoxin-induced fatal liver failure in a murine model; Ogushi I et al.; Endotoxin syndrome is a systemic inflammatory response mediated by inflammatory cytokines . Nuclear factor kappa B (NF-kappa B) is the dominant regulator of the production of these cytokines by inflammatory cells . The aim of this study was to assess the efficacy of in vivo transfer of synthetic double-stranded oligodeoxynucleotides (ODN) with high affinity against NF-kappa B (NF-kappa B/decoy/ODN) as a therapeutic strategy for treating endotoxin-induced fatal liver injury . Liver injury was induced by administration of lipopolysaccharide (LPS) to Propionibacterium acnes-primed BALB/C mice . NF-kappa B/decoy/ODN was transferred into the portal vein using a fusigenic liposome with hemagglutinating virus of Japan . NF-kappa B/decoy/ODN was preferentially transferred to Kupffer cells, and activation of NF-kappa B after the LPS challenge was suppressed, leading to decreased inflammatory cytokine production . As a result, the massive necrosis and hepatocyte apoptosis observed in the control mice was dramatically attenuated and the survival rate improved . In conclusion, NF-kappa B/decoy/ODN transfer in vivo effectively suppressed endotoxin-induced fatal liver injury in mice.

Immunol Lett, 2003 Aug 5, 88(2), 163 - 9
Treatment with Propionibacterium acnes modulates the late phase reaction of immediate hypersensitivity in mice; Braga EG et al.; The administration of killed Propionibacterium acnes suspension to mice enhances macrophage phagocytic and tumoricidal activities, have an adjuvant effect to antibody response and increases resistance to infection . Recent reports demonstrated that P . acnes treatment promotes IL-12 and IL-18 synthesis in mice inducing IFN-gamma release, enhancement of IgG2a switch and inhibition of Th2 cell expansion . These findings led us to investigate whether P . acnes could modulate hypersensitivity type I reaction observed in a murine model . Animals were implanted with heat coagulated hen's egg white (HEW) into the subcutaneous tissue, followed by OVA-challenge in the footpad . The observed reaction was characterized by elevated Th2 cytokine levels, especially IL-4 and increase in eosinophil infiltration as occurs in the late phase reaction (LPR) of type I hypersensitivity, a pattern observed in allergic asthma in human . Two different biological effects were induced by killed P . acnes depending on the experimental protocol used . When mice were treated with one dose of P . acnes per week during 3 weeks and the last dose administrated at the same time of HEW implantation, a strong adjuvant effect on type I hypersensitivity reaction with intense eosinophilic infiltration was observed . On the other hand, when the HEW implant was made 1 week after the administration of the last dose of P . acnes, animals developed a typical delayed type hypersensitivity reaction, and a cytokines pattern characteristic of the Th1 immune response.

J Surg Res, 2003 Jun 1, 112(1), 102 - 10
Effects of endotoxin tolerance on Propionibacterium acnes-primed lipopolysaccharide hepatic injury; Margenthaler JA et al.; BACKGROUND: Prior administration of the Gram-positive bacteria Propionibacterium acnes (PA) results in hypersensitivity and hepatocyte necrosis to a subsequent low dose of lipopolysaccharide (LPS) . Endotoxin tolerance has been shown to prevent lethality after ischemia/reperfusion injuries, sepsis, and endotoxic shock . We investigated whether prior induction of LPS tolerance could prevent subsequent PA-priming and LPS-induced death . The levels of known effector cytokines possibly responsible for these changes were measured . METHODS: C57BL/6 (B6) mice were given heat-killed PA (0.5 mg/mouse) followed 7 days later by LPS (20 microg/mouse) . In parallel experiments, B6 mice were pretreated with a single 20 microg/mouse dose of LPS (lethal dose = 800 microg/mouse) 7 days prior to PA priming . Animal survival, liver and spleen weights, and histology were examined . Cytokine levels of the inflammatory cytokines interferon-alpha, tumor necrosis factor-gamma, interleukin (IL)-6, and IL-12 and the anti-inflammatory cytokines IL-4 and IL-10 were measured by enzyme-linked immunosorbent assay and by reverse-transcription polymerase chain reaction . RESULTS: Hepatomegaly, splenomegaly, and hepatocyte necrosis with death developed in all PA-primed B6 mice challenged with LPS . However, 83% of B6 mice given a tolerizing dose of LPS prior to PA survived (P < 0.01) without any increase in liver or spleen weights and without histological evidence of necrosis . Markedly decreased in vivo and in vitro inflammatory (interferon-alpha, tumor necrosis factor-gamma, IL-6, and IL-12) cytokine levels corresponded with survival in the LPS-tolerant mice . Endotoxin tolerance and subsequent survival were also associated with an increase in anti-inflammatory (IL-4 and IL-10) mRNA expression . CONCLUSIONS: Lethal PA-primed LPS-induced hepatic injury can be prevented by administering a tolerizing dose of LPS prior to PA-priming . LPS protects the liver by preventing hepatic mononuclear cellular infiltration, reducing the production of the toxic proinflammatory cytokines, and inducing the production of endogenous anti-inflammatory cytokines.

J Cosmet Laser Ther, 2003 Jun, 5(2), 111 - 7
The effective treatment of acne vulgaris by a high-intensity, narrow band 405-420 nm light source; Elman M et al.; BACKGROUND: Available topical treatments are slow and frequently irritating . Oral therapies may be associated with increased bacterial resistance (antibiotics) or possible severe side effects (oral isotretinoin) . In vitro and in vivo exposure of acne bacteria to 405-420 nm ultraviolet (UV) free blue light results in the photo-destruction of these bacteria through the effects on the porphyrins produced naturally by Propionibacterium acnes . A novel, high-intensity, narrow band 420 nm UV free blue light has been shown to decrease inflammatory acne lesions after eight bi-weekly treatments . OBJECTIVES: To examine the effects of high-intensity, narrow band 420 nm UV free blue light (ClearLight) on inflammatory acne lesions . METHODS: Three studies were carried out to examine the clinical effects of high-intensity, narrow band blue light on papulo-pustular acne: the split-face dose-response study, the full-face open trial and the split-face, double-blind controlled study . The studies enrolled 10, 13 and 23 patients respectively . RESULTS: The data show more than an 80% response to 420 nm acne phototherapy with a significant reduction of 59-67% of inflammatory acne lesions after only eight treatments of 8-15 minutes . The reduction in lesions was steady in the follow-ups at 2, 4 and 8 weeks after the end of therapy . Prolonged remission was evident in the 8 weeks after the end of therapy . No adverse effects or patient discomfort were noted in any of the patients . CONCLUSIONS: Acne phototherapy by high intensity, narrow band 405-420 nm light is proven to be an attractive, fast, effective, non-invasive alternative to current topical and parenteral anti-acne remedies.

J Drugs Dermatol, 2002 Sep, 1(2), 153 - 7
A new treatment for acne vulgaris combining benzoyl peroxide with clindamycin; Tschen E et al.; Topical acne therapies are widely used for the treatment of mild to moderately severe acne vulgaris . However, many available treatments have limitations associated with their use, including lengthy time to response, cosmetic acceptability, and photosensitivity . Combinations of topical antibiotics and comedolytics are especially useful, but some formulations have stability challenges . A new combination formulation that contains 1% clindamycin and 5% benzoyl peroxide (BenzaClin Topical Gel) is currently available . In clinical trials, clinical improvement occurred at the first two follow-up visits and continued throughout treatment . In addition, combination therapy with clindamycin/benzoyl peroxide gel rapidly reduces Propionibacteria acnes counts and suppresses the emergence of clindamycin-resistant P . acnes . This formulation is stable at room temperature for up to 2 months after compounding . The aqueous gel vehicle is less drying, and there is no photosensitivity associated with its use . This study compares the combination treatment of 1% clindamycin and 5% benzoyl peroxide topical gel with other therapeutic options for mild to moderately severe acne vulgaris.

Appl Environ Microbiol, 2003 Jul, 69(7), 3809 - 18
Susceptibility and adaptive response to bile salts in Propionibacterium freudenreichii: physiological and proteomic analysis; Leverrier P et al.; Tolerance to digestive stresses is one of the main factors limiting the use of microorganisms as live probiotic agents . Susceptibility to bile salts and tolerance acquisition in the probiotic strain Propionibacterium freudenreichii SI41 were characterized . We showed that pretreatment with a moderate concentration of bile salts (0.2 g/liter) greatly increased its survival during a subsequent lethal challenge (1.0 g/liter, 60 s) . Bile salts challenge led to drastic morphological changes, consistent with intracellular material leakage, for nonadapted cells but not for preexposed ones . Moreover, the physiological state of the cells during lethal treatment played an important role in the response to bile salts, as stationary-phase bacteria appeared much less sensitive than exponentially growing cells . Either thermal or detergent pretreatment conferred significantly increased protection toward bile salts challenge . In contrast, some other heterologous pretreatments (hypothermic and hyperosmotic) had no effect on tolerance to bile salts, while acid pretreatment even might have sensitized the cells . Two-dimensional electrophoresis experiments revealed that at least 24 proteins were induced during bile salts adaptation . Identification of these polypeptides suggested that the bile salts stress response involves signal sensing and transduction, a general stress response (also triggered by thermal denaturation, oxidative toxicity, and DNA damage), and an alternative sigma factor . Taken together, our results provide new insights into the tolerance of P . freudenreichii to bile salts, which must be taken into consideration for the use of probiotic strains and the improvement of technological processes.

J Pediatr Orthop B, 2003 Jul, 12(4), 284 - 7
Subacute Propionibacterium acnes osteomyelitis of the spine in an adolescent; Do TT et al.; Moderate to severe facial acne is caused by infection with Propionibacterium acnes, an organism that has also been implicated in subacute osteomyelitis . The symptoms are often indolent in nature, but slowly progressive . We present a case report of subacute P . acnes osteomyelitis at our institution . A high index of suspicion and an extended incubation time are required for diagnosis . Treatment usually requires irrigation and debridement, with or without antibiotics.

Infection, 2003 Jun, 31(3), 184 - 5
Pacemaker endocarditis due to Propionibacterium acnes; Zedtwitz-Liebenstein K et al.; Propionibacterium acnes belongs to the cutaneous flora of humans; it is often considered to be contaminant but has also been found to be a pathogen in human diseases . It is an uncommon causal agent in infective endocarditis and appears to have a predilection for prosthetic valves and foreign bodies . We describe a case of pacemaker endocarditis which shows that so-called harmless bacteria like P . acnes must be considered to be potential pathogens.

Cutis, 2003 May, 71(5), 353 - 4
Lasers, light, and acne; Hirsch RJ et al.; Acne vulgaris is a highly prevalent disease with significant potential for physical and emotional scarring . Acne lesions have long been noted to improve after exposure to sunlight . This improvement may be secondary to activation of endogenous porphyrins produced by Propionibacterium acnes . Recently, several investigators have presented studies in which light of particular wavelengths has been used to treat acne vulgaris . In this article, we review the results of these studies as we look to the future of light-based acne treatment.

Vet Ther, 2003 Spring, 4(1), 5 - 11
Increases in cytokine and antimicrobial peptide gene expression in horses by immunomodulation with Propionibacterium acnes; Davis EG et al.; Immunomodulation with Propionibacterium acnes is used for prophylaxis of respiratory disease or in horses suffering from chronic pulmonary inflammation; however, the mechanism for this response is poorly understood . Semiquantitative reverse transcriptase-polymerase chain reaction assays were used to evaluate gene expression of interleukin (IL)-2, IL-10, interferon (IFN)-gamma, and NK-lysin in healthy horses treated with P . acnes . Findings in the study indicated that horses treated with a P . acnes-based immunomodulator exhibited increased IFN-gamma and NK-lysin gene expression in peripheral blood mononuclear cells . These results suggest that part of the immunostimulating properties of a P . acnes-based immunomodulator is derived from enhanced gene expression of the type-1 cytokine IFN-gamma and NK-lysin, an antimicrobial peptide.

EMBO J, 2003 May 15, 22(10), 2334 - 47
Transcarboxylase 12S crystal structure: hexamer assembly and substrate binding to a multienzyme core; Hall PR et al.; Transcarboxylase from Propionibacterium shermanii is a 1.2 MDa multienzyme complex that couples two carboxylation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate, yielding propionyl-CoA and oxaloacetate . The 1.9 A resolution crystal structure of the central 12S hexameric core, which catalyzes the first carboxylation reaction, has been solved bound to its substrate methylmalonyl-CoA . Overall, the structure reveals two stacked trimers related by 2-fold symmetry, and a domain duplication in the monomer . In the active site, the labile carboxylate group of methylmalonyl-CoA is stabilized by interaction with the N-termini of two alpha-helices . The 12S domains are structurally similar to the crotonase/isomerase superfamily, although only domain 1 of each 12S monomer binds ligand . The 12S reaction is similar to that of human propionyl-CoA carboxylase, whose beta-subunit has 50% sequence identity with 12S . A homology model of the propionyl-CoA carboxylase beta-subunit, based on this 12S crystal structure, provides new insight into the propionyl-CoA carboxylase mechanism, its oligomeric structure and the molecular basis of mutations responsible for enzyme deficiency in propionic acidemia.

Paediatr Drugs, 2003, 5(5), 301 - 13
Guidelines for the management of acne vulgaris in adolescents; Goulden V; This article reviews the treatment of acne in adolescents . The choice of therapy should be principally based on the type of lesion and the severity of the acne, but psychosocial disability relating to the disease and the presence of scarring may also influence the approach to treatment.Mild acne generally requires topical treatment only . Benzoyl peroxide, azelaic acid, and antibacterials are generally used for inflammatory lesions . Topical retinoids are particularly effective for noninflamed lesions, and combination therapies are useful for mixed lesions.Moderately severe acne generally requires oral antibacterials . Tetracyclines/oxytetracycline and erythromycin are usually the first-line antibacterials . Second-generation tetracyclines, such as lymecycline, doxycycline, and minocycline, show improved absorption . Minocycline has the advantage of being rarely associated with Propionibacterium acnes antibacterial resistance, but can occasionally lead to potentially serious adverse effects . Trimethoprim is a useful third-line antibacterial therapy for patients resistant to other antibacterial therapies . Benzoyl peroxide should generally be used in combination with oral antibacterials as this has been shown to reduce the development of antibacterial resistance.For severe nodular acne, isotretinoin is the treatment of choice . In addition, over recent years dermatologists have increasingly used this drug to treat patients with moderate acne which has not responded to other systemic therapies, particularly when associated with scarring or significant psychological disability . However, this use is outside the current license of the drug . Isotretinoin is associated with a number of serious adverse effects and careful monitoring of patients during therapy is required.Physical therapies for the treatment of acne nodules and macrocomedones are also important adjuncts to drug therapies.

Anesth Analg, 2003 May, 96(5), 1486 - 8, table of contents
Lumbar spondylodiscitis caused by Propionibacterium acnes after epidural obstetric analgesia; Hernandez-Palazon J et al.; IMPLICATIONS: We report a case of Propionibacterium acnes spondylodiscitis after the placement of an epidural catheter for obstetric analgesia . This observation should alert the anesthesiologist to the fact that infection, although rare, may occur after uneventful epidural analgesia in the healthy parturient and reinforces the importance of aseptic technique during epidural catheter insertion.

Am J Clin Dermatol, 2003, 4(5), 307 - 14
Antibacterial therapy for acne: a guide to selection and use of systemic agents; Tan HH; Acne vulgaris is a very common disorder, affecting virtually every adolescent at some point in time . Systemic antibacterials have been used in the treatment of acne for many years, and there are several commonly used antibacterials which have established efficacy and safety records . In recent years, the issue of antibacterials resistance has become more prominent, especially with concerns that Propionibacterium acnes can transfer antibacterials resistance to other bacteria within the resident skin flora.Commonly used antibacterials include tetracycline, doxycycline, minocycline, erythromycin (and other macrolides) and trimethoprim/sulfamethoxazole (cotrimoxazole) . The choice of antibacterial should take into account efficacy, cost-effectiveness, benefit-risk ratios, patient acceptability and the potential for the development of resistance.Poor clinical response can be the result of poor compliance, inadequate duration of therapy, development of gram-negative folliculitis, resistance of P . acnes to the antibacterial(s) administered, or a high sebum excretion rate.In order to help prevent the development of resistance a number of measures should be undertaken: antibacterials are prescribed for an average of 6 months; if retreatment is required, utilize the same antibacterial; generally, antibacterials should be given for at least 2 months before considering switching due to poor therapeutic response; concomitant use of oral and topical chemically-dissimilar antibacterials should be avoided (try benzoyl peroxide and/or retinoids instead) and systemic isotretinoin should be considered if several antibacterials have been tried without success.

Lett Appl Microbiol, 2003, 36(5), 327 - 31
Probiotics for the skin: a new area of potential application?
Ouwehand AC, Batsman A, Salminen S.
AIMS: The current study aimed at assessing, in vitro, the potential use of probiotics for the skin . METHODS AND RESULTS: Propionibacteria were chosen as potential probiotics as they are members of the normal cutaneous microbiota . Dairy strains were chosen because of their documented safe use . Production of anti-microbial substances was assessed, against selected skin pathogens . Only production of organic acids was detected . Two of the tested strains were found to exhibit high adhesion to human keratin, in vitro . Despite this high adhesion, no inhibition of skin pathogen adhesion to human keratin was observed . CONCLUSIONS: The current strains assessed may not be optimal for use as skin probiotics . However, the results of the study show that the methodology works for investigating this kind of application . SIGNIFICANCE AND IMPACT OF THE STUDY: Methods for selecting probiotics for potential application on the skin are presented.

Br J Dermatol, 2003 Mar, 148(3), 467 - 78
Antibiotic-resistant acne: lessons from Europe; Ross JI et al.; BACKGROUND: Propionibacterium acnes and P . granulosum are widely regarded as the aetiological agents of inflammatory acne . Their proliferation and metabolism are controlled using lengthy courses of oral and/or topical antibiotics . Despite numerous reports of skin colonization by antibiotic-resistant propionibacteria among acne patients, accurate prevalence data are available only for the U.K . OBJECTIVES: To determine the prevalence of skin colonization by antibiotic-resistant propionibacteria among acne patients and their contacts from six European centres . METHODS: Skin swabs were collected from 664 acne patients attending centres in the U.K., Spain, Italy, Greece, Sweden and Hungary . Phenotypes of antibiotic-resistant propionibacteria were determined by measuring the minimum inhibitory concentrations (MIC) of a panel of tetracycline and macrolide, lincosamide and streptogramin B (MLS) antibiotics . Resistance determinants were characterized by polymerase chain reaction (PCR) using primers specific for rRNA genes and erm(X), followed by nucleotide sequencing of the amplified DNA . RESULTS: Viable propionibacteria were recovered from 622 patients . A total of 515 representative antibiotic-resistant isolates and 71 susceptible isolates to act as control strains were characterized phenotypically . The prevalence of carriage of isolates resistant to at least one antibiotic was lowest in Hungary (51%) and highest in Spain (94%) . Combined resistance to clindamycin and erythromycin was much more common (highest prevalence 91% in Spain) than resistance to the tetracyclines (highest prevalence 26.4% in the U.K.) . No isolates resistant to tetracycline were detected in Italy, or in Hungary . Overall, there were strong correlations with prescribing patterns . Prevalence of resistant propionibacteria on the skin of untreated contacts of the patients varied from 41% in Hungary to 86% in Spain . Of the dermatologists, 25 of 39 were colonized with resistant propionibacteria, including all those who specialized in treating acne . None of 27 physicians working in other outpatient departments harboured resistant propionibacteria . CONCLUSIONS: The widespread use of topical formulations of erythromycin and clindamycin to treat acne has resulted in significant dissemination of cross-resistant strains of propionibacteria . Resistance rates to the orally administered tetracycline group of antibiotics were low, except in Sweden and the U.K . Resistant genotypes originally identified in the U.K . are distributed widely throughout Europe . Antibiotic-resistant propionibacteria should be considered transmissible between acne-prone individuals, and dermatologists should use stricter cross-infection control measures when assessing acne in the clinic.

Skin Pharmacol Appl Skin Physiol, 2003 Mar-Apr, 16(2), 84 - 90
Anti-acne effects of Oriental herb extracts: a novel screening method to select anti-acne agents; Nam C et al.; The acne-therapeutic effects of Oriental herb extracts were investigated in terms of antichemotactic effect on polymorphonuclear leucocytes, antilipogenic actions, antibacterial activity against Propionibacterium acnes and resistance induction potency in the bacteria . The ethanol extract (0.01%) of Angelica dahurica markedly suppressed neutrophil chemotaxis, comparable to the effect of erythromycin (0.01%), whereas a strong antilipogenic effect was obtained with rhizoma coptidis (Coptis chinensis) extract (0.01%), leading to a higher efficacy than that of retinoic acid (0.01%) . Interestingly, only Glycyrrhiza glabra showed a remarkable antibacterial activity against P . acnes, resulting in negligible induction of resistance, in comparison with a marked development of resistance in the bacteria treated with erythromycin . We suggest that an appropriate formulation containing A . dahurica, rhizoma coptidis and G . glabra could be helpful for the prevention and treatment of acne lesions .

Phytomedicine, 2003 Jan, 10(1), 34 - 8
Inhibition of Propionibacterium acnes-induced mediators of inflammation by Indian herbs; Jain A et al.; Propionibacterium acnes, an anaerobic pathogen, plays an important role in the pathogenesis of acne by inducing certain inflammatory mediators . These mediators include reactive oxygen species (ROS) and pro-inflammatory cytokines . In the present study, ROS, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were used as the major criteria for the evaluation of anti-inflammatory activity . To prove the anti-inflammatory effects of herbs, polymorphonuclear leukocytes (PMNL) and monocytes were treated with culture supernatant of P . acnes in the presence or absence of herbs . It was found that Rubia cordifolia, Curcuma longa, Hemidesmus indicus, and Azadirachta indica caused a statistically significant suppression of ROS from PMNL . Sphaeranthus indicus caused a smaller, still significant suppression of ROS . Aloe vera had no effect on ROS production . In the case of proinflammatory cytokine-induced monocytes, maximum suppression was shown by Azadirachta indica and Sphaeranthus indicus, followed by Hemidesmus indicus, Rubia cordifolia, and Curcuma longa . Aloe vera showed insignificant inhibitory activity . Thus, these herbs shows anti-inflammatory activity by suppressing the capacity of P . acnes-induced ROS and pro-inflammatory cytokines, the two important inflammatory mediators in acne pathogenesis.

FEMS Immunol Med Microbiol, 2003 Jan 21, 35(1), 17 - 24
Eradication of Propionibacterium acnes by its endogenic porphyrins after illumination with high intensity blue light; Ashkenazi H et al.; Propionibacterium acnes is a Gram-positive, microaerophilic bacterium that causes skin wounds . It is known to naturally produce high amounts of intracellular porphyrins . The results of the present study confirm that the investigated strain of P . acnes is capable of producing endogenic porphyrins with no need for any trigger molecules . Extracts from growing cultures have demonstrated emission peaks around 612 nm when excited at 405 nm, which are characteristic for porphyrins . Endogenic porphyrins were determined and quantified after their extraction from the bacterial cells by fluorescence intensity and by elution retention time on high-performance liquid chromatography (HPLC) . The porphyrins produced by P . acnes are mostly coproporphyrin, as shown by the HPLC elution patterns . Addition of delta-aminolevulinic acid (ALA) enhanced intracellular porphyrin synthesis and higher amounts of coproporphyrin have been found . Eradication of P . acnes by its endogenic porphyrins was examined after illumination with intense blue light at 407-420 nm . The viability of 24 h cultures grown anaerobically in liquid medium was reduced by less than two orders of magnitude when illuminated once with a light dose of 75 J cm(-2) . Better photodynamic effects were obtained when cultures were illuminated twice or three times consecutively with a light dose of 75 J cm(-2) and an interval of 24 h between illuminations . The viability of the culture under these conditions decreased by four orders of magnitude after two illuminations and by five orders of magnitude after three illuminations . When ALA-triggered cultures were illuminated with intense blue light at a light dose of 75 J cm(-2) the viability of the treated cultures decreased by seven orders of magnitude . This decrease in viability can occur even after a single exposure of illumination for the indicated light intensity . X-ray microanalysis and transmission electron microscopy revealed structural damages to membranes in the illuminated P . acnes . Illumination of the endogenous coproporphyrin with blue light (407-420 nm) apparently plays a major role in P . acnes photoinactivation . A treatment protocol with a series of several illuminations or illumination after application of ALA may be suitable for curing acne . Treatment by both pathways may overcome the resistance of P . acnes to antibiotic treatment.

Dermatology, 2003, 206(1), 54 - 6
Propionibacterium acnes resistance: a worldwide problem; Eady EA et al.; Antibiotic therapy directed against Propionibacterium acnes has been a mainstay of treatment for more than 40 years . Despite years of widespread use of systemic tetracyclines and erythromycin, change in P . acnes sensitivity to antibiotics was not seen until the early 1980s . The first clinically relevant changes in P . acnes antibiotic sensitivity were found in the USA shortly after the introduction of topical formulations of erythromycin and clindamycin . By the late 1980s, P . acnes strains with very high MIC levels for erythromycin and elevated MICs for tetracycline were increasingly found in the UK and the USA . Mutations in the genes encoding the 23S and 16S subunits of ribosomal RNA were first identified in the UK and also seen in a recent survey from clinics in Europe, Japan, Australia and the USA . In addition, strains were found in which these known mutations could not be identified, indicating that as yet unidentified resistance mechanisms have evolved . These findings indicate the need to develop strategies to minimize the use of antibiotics in acne therapy .

Dermatology, 2003, 206(1), 17 - 23
New aspects in acne inflammation; Toyoda M et al.; There is ample clinical evidence suggesting that the nervous system such as emotional stress can influence the course of acne . We examined possible participation of cutaneous neurogenic factors including neuropeptides, neuropeptide-degrading enzymes and neurotrophic factors, in association with inflammation in the pathogenesis of acne . Immunohistochemical studies revealed that substance P (SP)-immunoreactive nerve fibers were in close apposition to the sebaceous glands, and that neutral endopeptidase (NEP) was expressed in the germinative cells of the sebaceous glands in the skin from acne patients . Nerve growth factor showed immunoreactivity only within the germinative cells . In addition, an increase in the number of mast cells and a strong expression of endothelial leukocyte adhesion molecule-1 on the postcapillary venules were observed in adjacent areas to the sebaceous glands . In vitro, the levels and the expression of stem cell factor by fibroblasts were upregulated by SP . When organ-cultured normal skin specimens were exposed to SP, we observed significant increases in the sizes of the sebaceous glands and in the number of sebum vacuoles in sebaceous cells . Furthermore, supplementation of SP to organ-cultured skin induced expression of NEP, and we demonstrated the subcellular localization of NEP in the endoplasmic reticulum and the Golgi apparatus within the sebaceous germinative cells using preembedding immunoelectron microscopy . These findings suggest that SP may stimulate lipogenesis of the sebaceous glands which may be followed by proliferation of Propionibacterium acnes, and may yield a potent influence on the sebaceous glands by provocation of inflammatory reactions via mast cells . Thus, cutaneous neurogenic factors should contribute to onset and/or exacerbation of acne inflammation .

J Leukoc Biol, 2003 Feb, 73(2), 213 - 24
Interleukin-18; Gracie JA et al.; Interleukin-18 (IL-18), a recently described member of the IL-1 cytokine superfamily, is now recognized as an important regulator of innate and acquired immune responses . IL-18 is expressed at sites of chronic inflammation, in autoimmune diseases, in a variety of cancers, and in the context of numerous infectious diseases . This short review will describe the basic biology of IL-18 and thereafter address its potential effector and regulatory role in several human disease states including autoimmunity and infection . IL-18, previously known as interferon-gamma (IFN-gamma)-inducing factor, was identified as an endotoxin-induced serum factor that stimulated IFN-gamma production by murine splenocytes {(1) } . IL-18 was cloned from a murine liver cell cDNA library generated from animals primed with heat-killed Propionibacterium acnes and subsequently challenged with lipopolysaccharide {(2) } . Nucleotide sequencing of murine IL-18 predicted a precursor polypeptide of 192 amino acids lacking a conventional signal peptide and a mature protein of 157 amino acids . Subsequent cloning of human IL-18 cDNA revealed 65% homology with murine IL-18 {(3) } and showed that both contain an unusual leader sequence consisting of 35 amino acids at their N terminus.

Am J Clin Dermatol, 2003, 4(2), 75 - 80
The rationale for using a topical retinoid for inflammatory acne; Millikan LE; Both comedogenesis and the development of inflammatory lesions in acne vulgaris appear to be related to genetic as well as immune processes . The key regulatory cytokine, interleukin-1alpha, has recently been documented as playing a major role in both the hypercornification and the orchestration of immune factors, ultimately resulting in noninflammatory and inflammatory lesions . Topical retinoids, such as tretinoin, and topical retinoid analogs, such as adapalene and tazarotene, help normalize the abnormal follicular keratinocyte desquamation - a key pathophysiologic factor in comedogenesis . This normalization also helps mitigate against the development of a propitious microenvironment for Propionibacterium acnes . Preclinical data suggest that topical retinoids and retinoid analogs may also have direct anti-inflammatory effects . A wealth of clinical data confirms that topical retinoids and retinoid analogs significantly reduce inflammatory lesions . Comparative clinical trials also demonstrate that adapalene has the best cutaneous tolerability profile of all these agents . Optimal therapy for inflammatory acne would involve the use of topical retinoids or retinoid analogs combined with oral or topical antibacterials.

Dermatol Online J . 2002 Oct;8(2):2.
Anti-inflammatory effects of erythromycin and tetracycline on Propionibacterium acnes induced production of chemotactic factors and reactive oxygen species by human neutrophils; Jain A et al.; Propionibacterium acnes (P . acnes), an anaerobic pathogen, plays an important role in the pathogenesis of acne and seems to initiate the inflammatory process by producing neutrophil chemotactic factors (NCF) . Once neutrophils attracted by bacterial chemoattractants reach the inflamed site, they release inflammatory mediators such as lysosomal enzymes and reactive oxygen species (ROS) . Previously, it has been shown that antibiotics may affect acne by means other than their anti-bacterial effects . Thus, we investigated the effect of subminimal inhibitory concentration (sub-MIC) of tetracycline and erythromycin on production of NCF and ROS . NCF was tested in vivo in a mouse model and ROS was estimated on human PMNL in vitro, by nitroblue tetrazolium dye reduction test (NBT) and cytochrome-C reduction test . Tetracycline (CS-T) and Erythromycin (CS-E) treated cultures showed a significant reduction of 35.8% and 58.3% in NCF production respectively, as compared to P . acnes stimulated cultures . Tetracycline and erythromycin at their sub-MIC also significantly inhibited release of ROS from human PMNL . Thus, tetracycline and erythromycin, besides having antibacterial activity, also have an anti-inflammatory action . These antibiotics reduce the capacity of P . acnes to produce NCF, as well decrease its ability to induce ROS from PMNL.

J Endotoxin Res, 2002, 8(5), 337 - 342
Enhancement of endotoxin activity by muramyldipeptide; Takada H et al.; Synthetic muramyldipeptide (MDP), the minimum structural moiety of bacterial peptidoglycan for adjuvant and related activities, sensitized mice for two types of lethal shock induced by lipopolysaccharide (LPS): an early anaphylactoid shock and late endotoxin shock . In relation to the late reaction in MDP-primed mice, enhanced production of inflammatory cytokines was induced in response to various bacterial components . MDP showed a priming effect in mice not only when administered parentally but also via the oral route . MDP activated human monocytic THP-1 cells in a CD14-, Toll-like receptor 2 (TLR2)- and TLR4-independent manner to increase expression of MyD88, a common adaptor and signaling molecule for TLRs, and exhibited synergistic cytokine inducing effects with TLR4 agonists (LPS, synthetic lipid A), TLR2 agonist (synthetic lipopeptide), and TLR9 agonist (bacterial CpGDNA) in THP-1 cells in culture . Consistent with these findings, MDP primed TLR2 knockout mice as well as wild-type controls, but not TLR4-mutated C3H/HeJ mice, to enhance production of tumor necrosis factor-alpha upon stimulation with synthetic lipid A . In contrast to the BCG- and Propionibacterium acnes-priming system, MDP primed mice in an interferon-gamma-independent manner . Further studies are required to elucidate the mechanisms of the synthetic and priming activities of MDP for various bacterial components.

Curr Microbiol, 2003 Feb, 46(2), 141 - 5
Glucose fermentation by Propionibacterium microaerophilum: effect of pH on metabolism and bioenergetic; Koussemon M et al.; pH affected significantly the growth and the glucose fermentation pattern of Propionibacterium microaerophilum . In neutral conditions (pH 6.5-7.5), growth and glucose fermentation rate (qs) were optimum producing propionate, acetate, CO(2), and formate {which together represented 90% (wt/wt) of the end products}, and lactate representing only 10% (wt/wt) of the end products . In acidic conditions, propionate, acetate, and CO(2) represented nearly 100% (wt/wt) of the fermentation end products, whereas in alkaline conditions, a shift of glucose catabolism toward formate and lactate was observed, lactate representing 50% (wt/wt) of the fermentation end products . The energy cellular yields ( Y(X/ATP)), calculated (i) by taking into account extra ATP synthesized through the reduction of fumarate into succinate, was 6.1-7.2 g mol(-1) . When this extra ATP was omitted, it was 11.9-13.1 g mol(-1) . The comparison of these values with those of Y(X/ATP) in P . acidipropionici and other anaerobic bacteria suggested that P . microaerophilum could not synthesize ATP through the reduction of fumarate into succinate and therefore differed metabolically from P . acidipropionici.

Int J Syst Evol Microbiol, 2002 Nov, 52(Pt 6), 1925 - 7
Propionimicrobium gen . nov., a new genus to accommodate Propionibacterium lymphophilum (Torrey 1916) Johnson and Cummins 1972, 1057AL as Propionimicrobium lymphophilum comb . nov; Stackebrandt E et al.; Based upon significant differences in chemotaxonomic properties, i.e., amino acid composition of peptidoglycan, fatty acids and base composition of DNA, and supported by the phylogenetic position of the 165 rDNA sequence the species Propionibacterium lymphophilum was reclassified as Propionimicrobium lymphophilum comb . nov.

J Shoulder Elbow Surg, 2002 Nov-Dec, 11(6), 605 - 8
Infection after mini-open rotator cuff repair; Herrera MF et al.; A consecutive case series from 2 institutions of patients with postoperative wound infections after mini-open rotator cuff repair was reviewed . Between 1991 and 2000, 360 patients underwent mini-open rotator cuff repair after arthroscopic subacromial decompression . Seven patients had postoperative infection develop (1.9%) . All patients were men, with a mean age of 55 years (range, 40-64 years) . Treatment included serial irrigation and debridement, long-term intravenous antibiotics, and revision rotator cuff repair . Mean follow-up after definitive treatment was 32 months (range, 12-57 months) . Propionibacter acnes was present in 6 of 7 patients (86%) with infections . The initial rotator cuff repair was disrupted in 4 shoulders and intact in 3 . A revision rotator cuff repair was performed at the final irrigation and debridement in all 4 shoulders . Results were 100% satisfactory . The mean American Shoulder and Elbow Surgeons pain score improved from 7 (range, 6-9) preoperatively to 1 (range, 0-2) . The mean final score was 95 . Because these infections were noted to occur only in arthroscopically assisted rotator cuff repairs, a second preparation and draping were introduced as routine protocol . No postoperative infections have occurred in the ensuing 200 mini-open rotator cuff repairs.

Appl Microbiol Biotechnol, 2002 Dec, 60(4), 481 - 4 Epub 2002 Oct 18.
Cell-adhered conjugated linoleic acid regulates isomerization of linoleic acid by resting cells of Propionibacterium freudenreichii; Rainio A et al.; The microbiological isomerization of linoleic acid (LA) to conjugated linoleic acid (CLA) was studied in resting cell suspensions of a propionibacterium and micellar LA to identify factors critical in the isomerization efficiency . These suspensions, containing cells 5x10(10) colony-forming units ml(-1) and 510 micro g LA ml(-1), isomerized about 90% of LA to CLA . However, the yield was not improved with higher amounts of micellar LA, suggesting that the cells had a fixed capacity to carry out the isomerization . This was explained by the fact that the CLA formed had a tendency to accumulate in the cell mass rather than in the aqueous micellar phase during the isomerization . Concomitantly, cell viability and isomerization rates were gradually reduced . Upon cessation of the reaction, about 46% of all the CLA formed was in the cell material . This accumulation to the cells was prevented by adding the detergent in excess to that required for micellization of LA . Then the cells remained viable, but the rate of isomerization was drastically lowered, due to impaired availability of LA from the fortified micellar phase to the cells . It was concluded that the phase distribution of substrate and product plays a critical role in the microbiological production of CLA.

J Pathol, 2002 Dec, 198(4), 541 - 7
In situ localization of Propionibacterium acnes DNA in lymph nodes from sarcoidosis patients by signal amplification with catalysed reporter deposition; Yamada T et al.; Sarcoidosis is a systemic granulomatous disease of unknown aetiology . Many genomes of Propionibacterium acnes and P . granulosum have been detected in lymph nodes from patients with sarcoidosis . In situ localization of propionibacterial genomes in sarcoid lymph nodes may help to establish an aetiological link between sarcoidosis and these indigenous bacteria . Formalin-fixed and paraffin-embedded biopsy samples of lymph nodes from nine patients with sarcoidosis, nine patients with tuberculosis, and nine patients with non-specific lymphadenitis as controls were examined by quantitative real-time PCR (QPCR) for P . acnes and by in situ hybridization (ISH) that used catalysed reporter deposition (CARD) for signal amplification with digoxigenin-labelled oligonucleotide probes that complemented 16S rRNA of P . acnes . The signals per 250 micro m(2) of tissue sections were counted from inside and outside the granulomas of sarcoidosis and tuberculosis and from control lymph nodes . The number of genomes by QPCR was examined for correlation with the mean signal count by ISH with CARD . In sarcoid samples, one or several signals were detected in the cytoplasm of some epithelioid cells in granulomas and of many mononuclear cells around granulomas . The mean signal counts were higher (p < 0.001) in granulomatous areas than in other areas of sarcoid lymph nodes . Even in their non-granulomatous areas, counts were higher than in granulomatous areas (p = 0.0023) and non-granulomatous areas (p < 0.001) of tuberculous lymph nodes and control lymph nodes (p = 0.0071) . Correlation between the results by QPCR and ISH with CARD was significant (r = 0.86, p < 0.001) . The accumulation of P . acnes genomes in and around sarcoid granulomas suggests that this indigenous bacterium may be related to the cause of granulomatous inflammation in sarcoidosis .

J Biol Chem, 2003 Feb 7, 278(6), 3948 - 56 Epub 2002 Nov 08.
Novel bacterial polar lipids containing ether-linked alkyl chains, the structures and biological properties of the four major glycolipids from Propionibacterium propionicum PCM 2431 (ATCC 14157T); Pasciak M et al.; Propionibacterium propionicum belongs to the "acnes group" of propionibacteria, which is currently considered as clinically important because of its growing potential in infections, in particular with those connected with immune system dysfunctions . Propionibacteria are thought to be actinomycete-like microorganisms and may still cause diagnostic difficulties . The chloroform-methanol extracts of the cell mass of P . propionicum (type strain) gave in TLC analysis the characteristic glycolipid profile containing four major glycolipids, labeled G(1) through G(4) . These polar lipids were found to be useful chemotaxonomic markers to differentiate P . propionicum from other cutaneous propionibacteria, in particular from strains of the acnes group . Glycolipids G(1)-G(4) were isolated and purified using gel-permeation chromatography, TLC, and high performance liquid chromatography, and their structures were elucidated by compositional and methylation analyses, specific chemical degradations, MALDI-TOF mass spectrometry, and (1)H NMR and (13)C NMR spectroscopy, including HMBC, TOCSY, HMQC, and NOESY experiments . Glycolipids G(2) and G(3) possess as backbone alpha-d-Glcp-(1 --> 3)-alpha-d-Glcp-(1 --> 1)-Gro (Gro, glycerol), in which position O-2 of the glycerol residue is acylated by a fatty acid (mainly C(15):0) while O-3 is substituted by an alkyl ether chain . In glycolipid G(3), an additional fatty acyl chain was linked to O-6 of the terminal glucose residue . Glycolipid G(4) was structurally related to G(2) but devoid of one glucose residue . Glycolipid G(1) was isolated in small amounts, and its structure was therefore deduced from MALDI-TOF-MS experiments alone, which revealed that it possessed the structure of G(2) but was lacking one fatty acid residue . In studies on the biological properties of P . propionicum glycolipids, the anti-P . propionicum rabbit antisera reacted in dot enzyme-immunoblotting test with G(2) and G(3) . Glycolipid G(3) was able to induce the delayed type of hypersensitivity . The results indicated that these novel ether linkage-containing polar glycolipids are immunogenic and possibly active in hypersensitivity, and thus, in pathogenesis.

Syst Appl Microbiol, 2002 Oct, 25(3), 386 - 95
Use of predictive modeling for Propionibacterium strain classification; Matte-Tailliez O et al.; Computed data analysis of biochemical or molecular profiles is currently used in studies of microbial taxonomy, epidemiology, and microbial diversity . We assessed the use of Partial Least Squares (PLS) regression for multivariate data analysis in bacteriology . We identified clear relationships between RAPD profiles of propionibacteria strains and their species classification, autolytic capacities, and their origins . The PLS regression also predicted species identity of some strains with RAPD profiles partially related to those of reference strains . The PLS analysis also allowed us to identify key characteristics to use to classify strains . PLS regression is particularly well adapted to i) describing a collection of bacterial isolates, ii) justifying bacterial groupings using several sets of data, and iii) predicting phenotypic characters of strains that have been classified by routine typing methods.

Biochem Biophys Res Commun, 2002 Nov 15, 298(5), 675 - 86
Gene expression profile analysis of the mouse liver during bacteria-induced fulminant hepatitis by a cDNA microarray system; Dong H et al.; Fulminant hepatic failure (FHF) is a disease characterized by sudden and severe impairment of liver function . To elucidate the mechanism involved in FHF, we adopted a murine model of FHF by administrating mice with heat-killed Propionibacterium acnes (P . acnes), followed by a low dose of lipopolysaccharide (LPS), and analyzed the dynamic change of gene expression profile of the murine liver using an in-house cDNA microarray system which contained most of the cDNAs encoding chemokines/cytokines and their receptors (33 chemokines/21 chemokine receptors, 28 cytokines/35 cytokine receptors) as well as 230 liver related proteins mostly selected by serial analysis of gene expression (SAGE) . Among them, 335 genes were found to differ by more than 2-fold in at least one time point comparing with normal liver . Hierarchical cluster analysis revealed that except for a few genes, such as heme oxygenase (HO)-1 and nicotinamide N-methyltransferase (NNMT) of which expression increased, the expression of most of the genes encoding drug metabolizing enzymes decreased with the progress of the disease . The expression of the genes encoding chemokines/cytokines was dramatically changed, such as Mig, IP-10, RANTES, TNF-alpha, and IFN-gamma . In addition, the expression of those that were not previously linked to this murine model was also identified to be changed . These include endogenous IL-18 binding protein (IL-18BP), CXCL16 (the ligand of Bonzo, CXCR6) as well as ESTs . Taken together this study has shown the systemic and comprehensive gene expression profile during FHF and may contribute to better understanding of the mechanism of FHF.

Cornea, 2002 Nov, 21(8), 812 - 7
Ocular surface inflammation induced by Propionibacterium acnes; Suzuki T et al.; PURPOSE: In the eye, is commonly isolated in the lid, conjunctiva, and meibomian gland secretion . Well known as a causative bacterium of granulomatous endophthalmitis and a potent inflammatory stimulus, reportedly induces a delayed-type hypersensitivity (DTH) response and forms granulomas in the liver and lung in animal models . In this study, we examined whether can induce a DTH response in the cornea . METHODS: Six- to 8-week-old female Lewis rats were immunized with heat-killed suspension of and assessed as to DTH response via ear challenge at 2 weeks after immunization . At 3 weeks after immunization, suspension was injected in the rat corneal stroma, which was then observed biomicroscopically at 6, 24, and 48 hours after injection . Phenol-killed suspension was also used for the comparison . Histological examination was also performed on the corneal tissues, using hematoxylin and eosin staining as well as immunohistochemical staining against CD4 and CD8 T cells . RESULTS: Rats immunized with suspension showed significantly higher ear swelling values at both the 24- and 48-hour measurements than did the naive controls (p < 0.005) . Massive cellular infiltration with stromal edema was observed biomicroscopically at 48 hours after injection of suspension in the corneal stroma . Histological study showed that the cell infiltration pattern was similar to that of DTH in the skin, i.e., neutrophils infiltrated at 6 hours, followed by mononuclear cells that, including macrophages and lymphocytes, increased and mixed with neutrophils, accompanied by stromal edema at 48 hours . Immunohistochemical study revealed that CD4 T-cell infiltration in the corneal stroma appeared to predominate over CD8 T-cell infiltration . CONCLUSIONS: These results indicate that can induce a DTH response in the cornea and may be a causative bacterium of ocular surface inflammation.

Dermatology, 2002, 205(3), 260 - 4
Inhibition of lipase activity in antibiotic-resistant propionibacterium acnes strains; Gloor M et al.; BACKGROUND AND OBJECTIVE: Erythromycin-sensitive and/or clindamycin-sensitive strains of Propionibacterium acnes show a reduced lipase production at levels below the minimal growth-inhibitory concentration (MIC) . The objective of this study was to determine whether erythromycin and clindamycin concentrations far below the MIC inhibit lipase production in P . acnes strains resistant to these antibiotics . METHODS: Of 42 P . acnes strains, 10 showed an MIC >256 micro g/ml for erythromycin . Two strains showed MICs of 0.19 and 0.25 micro g/ml, while the MIC of the remaining strains was <or=0.016 micro g/ml . Lipase activity was determined up to a concentration of 192 micro g/ml by cultivation on spirit blue agar + lipase reagent . The 10 strains whose erythromycin MIC was >256 micro g/ml were also tested for lipase inhibition by clindamycin . While this method fails to differentiate between inhibition of lipase production and inhibition of lipase activity, the absence of inhibition of lipase activity rules out inhibition of lipase production . RESULTS: Inhibition of lipolysis by sub-MIC concentrations was demonstrated only for clindamycin in 3 P . acnes strains . However, lipase inhibition was seen only at the dilution level immediately below the MIC . CONCLUSIONS: Resistant P . acnes strains with high erythromycin and/or clindamycin MICs can be ruled out to show in vitro inhibition of lipase production at antibiotic concentrations far below the MIC .

Transfus Med, 2002 Oct, 12(5), 303 - 9
Evaluation of the 3D BacT/ALERT automated culture system for the detection of microbial contamination of platelet concentrates; McDonald CP et al.; Bacterial transmission remains the major component of morbidity and mortality associated with transfusion-transmitted infections . Platelet concentrates are the most common cause of bacterial transmission . The BacT/ALERT 3D automated blood culture system has the potential to screen platelet concentrates for the presence of bacteria . Evaluation of this system was performed by spiking day 2 apheresis platelet units with individual bacterial isolates at final concentrations of 10 and 100 colony-forming units (cfu) mL-1 . Fifteen organisms were used which had been cited in platelet transmission and monitoring studies . BacT/ALERT times to detection were compared with thioglycollate broth cultures, and the performance of five types of BacT/ALERT culture bottles was evaluated . Sampling was performed immediately after the inoculation of the units, and 10 replicates were performed per organism concentration for each of the five types of BacT/ALERT bottles . The mean times for the detection of these 15 organisms by BacT/ALERT, with the exception of Propionibacterium acnes, ranged from 9.1 to 48.1 h (all 10 replicates were positive) . In comparison, the time range found using thioglycollate was 12.0-32.3 h (all 10 replicates were positive) . P . acnes' BacT/ALERT mean detection times ranged from 89.0 to 177.6 h compared with 75.6-86.4 h for the thioglycollate broth . BacT/ALERT, with the exception of P . acnes, which has dubious clinical significance, gave equivalent or shorter detection times when compared with the thioglycollate broth system . The BacT/ALERT system detected a range of organisms at levels of 10 and 100 cfu mL-1 . This study validates the BacT/ALERT microbial detection system for screening platelets . Currently, the system is the only practically viable option available for routinely screening platelet concentrates to prevent bacterial transmission.

Scand J Gastroenterol, 2002 Sep, 37(9), 1008 - 11
Influence of short-chain fatty acids on iron absorption by proximal colon; Bougle D et al.; BACKGROUND: Short-chain fatty acids produced by bacterial fermentation in the colon enhance the local absorption of cations, such as calcium, that could be used to improve the bioavailability of iron if a significant colonic absorption of iron were to occur . METHODS: Iron (iron gluconate, 100 microM) absorption by the caecum of the rat was compared with that in proximal sites of the small bowel using the Ussing chamber model; the influence of probiotic bacteria (Propionibacterium freudenreichii) on iron absorption was assessed and compared with that of two of their fermentation products (acetic and propionic acids) using the Ussing chamber and the ligated colon with gamma emitting iron as experimental models . RESULTS: The caecum absorbed less iron than the duodenum, but significantly more than the jejunum and ileum . This occurred mainly through an enhanced mucosal transfer of iron uptake . Propionibacteria enhanced iron absorption from the proximal colon; the same effect was observed in the presence of viable bacteria, or the culture medium free of viable bacteria, or acetate and propionate or propionate alone . CONCLUSIONS: The proximal colon could be a significant site available for iron absorption; this absorption can be enhanced by local production of short-chain fatty acids such as propionate.

Cardiology, 2002, 98(1-2), 1 - 5
Endocarditis due to anaerobic bacteria; Brook I; This review describes the microbiology, diagnosis and management of endocarditis due to anaerobic bacteria . Anaerobic bacteria are an uncommon but important cause of endocarditis . Most cases of anaerobic endocarditis are caused by anaerobic cocci, Propionibacterium acnes and Bacteroides fragilis group . Predisposing factors and signs and symptoms of endocarditis caused by anaerobic bacteria are similar to those seen in endocarditis with facultative anaerobic bacteria with the following exceptions: the gastrointestinal tract was the most common source for B . fragilis group endocarditis, the head and neck were the most common origin for Fusobacterium and Bacteroides spp., and the head and neck and genitourinary tract were the most common source for peptostreptococci . Complications with anaerobic endocarditis include valvular destruction, multiple mycotic aneurysms, aortic-ring abscess, aortitis, cardiogenic shock, dysrhythmias and septic shock . The mortality rate for patients with anaerobes endocarditis is 21-43% . Treatment of endocarditis involving anaerobic bacteria includes the use of antibiotic therapy effective against these organisms .

J Cutan Med Surg, 2003 Jan-Feb, 7(1), 31 - 7 Epub 2002 Oct 09.
A randomized, double-blind, multicenter, parallel group study to compare relative efficacies of the topical gels 3% erythromycin/5% benzoyl peroxide and 0.025% tretinoin/erythromycin 4% in the treatment of moderate acne vulgaris of the face; Gupta AK et al.; BACKGROUND: Combination treatments for acne vulgaris, such as Benzamycin (3% erythromycin/5% benzoyl peroxide) and Stievamycin (0.025% tretinoin/erythromycin 4%), reduce bacterial growth, which contributes to the inflammatory lesions typical of adolescent acne, and also decrease the epidermal cell compaction which may form the characteristic noninflammatory comedone . Both agents contain erythromycin to reduce the growth of Propionibacterium acnes in skin . Benzoyl peroxide has antibiotic activity as well as anticomedogenic properties . Tretinoin may increase the turnover of epidermal cells and loosen the cells compacted to form comedones . A combination preparation containing the two antibiotics may reduce the development of resistance; the combination preparation containing tretinoin and erythromycin will have an antibiotic effect as well as acting on differentiation . PATIENTS AND METHODS: This multicenter, randomized, double-blind, parallel group study compared the effectiveness of 3% erythromycin/5% benzoyl peroxide and 0.025% tretinoin/erythromycin 4%, each applied twice daily in patients with moderate acne vulgaris . Overall physician and patient ratings of severity of acne symptoms were performed at baseline and at weeks 2, 4, 8, and 12 . RESULTS: At baseline the two treatment groups had similar disease severity . The number of papules, pustules, and comedones was reduced in both treatment groups at week 12, and the reductions were not significantly different between the two comparators . Global physician rating of improvement was significantly higher in the 3% erythromycin/5% benzoyl peroxide group compared with the 0.025% tretinoin/erythromycin 4% group; however, there was no significant difference in global patient ratings between the two treatment groups . An aggregate score was produced, for both physician rating and patient rating, by adding up individual symptom severity ratings . Compared with 0.025% tretinoin/erythromycin 4%, 3% erythromycin/5% benzoyl peroxide provided significantly greater reduction in both physician- and patient-rated severity of acne symptoms; there was a significant difference between the two groups as early as week 2 . The 3% erythromycin/5% benzoyl peroxide demonstrated significantly greater reduction of erythema and scaling, as evaluated by the study physician, compared with tretinoin 0.025%/erythromycin 4% . Patients judged 3% erythromycin/5% benzoyl peroxide to have a significantly greater effect on redness, dryness, oiliness, and burning . CONCLUSION: In moderate acne vulgaris, 3% erythromycin/5% benzoyl peroxide may provide a greater beneficial effect than 0.025% tretinoin/erythromycin 4%.

Nippon Rinsho, 2002 Sep, 60(9), 1704 - 13
{Epithelioid cell granuloma in sarcoidosis: light and electron microscopic morphology}; Takemura T; Light and electron microscopic features of epithelioid cell granuloma in sarcoidosis were presented, focusing on the lymph node and the lung which are mostly involved . The distribution of granulomas is frequently conglomerated with occasionally central necrosis . Hamazaki-Wesenberg body in lymph node is considered to be closely associated with Propionibacterium acnes . Granuloma is encircled by reticulin fibers and collagen fibers within the granuloma are detected in electron microscopy . Granuloma may disappear but some develop hyalinization and fibrosis associated with lymphatic and vascular involvement and specific organ structure . Vascular endothelial growth factor is immunohistochemically demonstrated in granuloma, which may be related to microvascular dilatation and proliferation . Thus, epithelioid cell granulomas play an central role in fibrosis and microangiopathy in sarcoidosis.

Nippon Rinsho, 2002 Sep, 60(9), 1688 - 96
{Etiology of sarcoidosis}; Eishi Y; The cause(s) of sarcoidosis is unknown . Sarcoidosis seems to result from exposure of a genetically susceptible subject to a specific environmental antigen(s) . From biopsy samples of lymph nodes from patients with sarcoidosis, Propionibacterium acnes has been isolated in culture, and many genomes of P.acnes or P.granulosum have been detected by quantitative PCR . Antigen-specific mitogenic responses of peripheral blood mononuclear cells were induced in sarcoidosis patients but not in healthy controls, when recombinant proteins from a propionibacterial trigger factor were used as stimulators . Sarcoidosis may arise from a Th1 immune response to one or more antigens of propionibacteria in an individual with a hereditary or acquired abnormality of the immune system.

Infect Immun, 2002 Oct, 70(10), 5596 - 603
Beneficial or deleterious effects of a preexisting hypersensitivity to bacterial components on the course and outcome of infection; Gumenscheimer M et al.; Priming with heat-killed Propionibacterium acnes enhances the sensitivity of mice to lipopolysaccharide (LPS) and other biologically active bacterial components . We show that P . acnes priming has protective and deleterious effects on a subsequent serovar Typhimurium infection . It may result in a complete protection or prolonged survival, or it may accelerate mortality of the infected mice, depending on the number of serovar Typhimurium bacteria administered and on the degree of LPS hypersensitivity at the time of infection . Both effects of P . acnes-induced hypersensitivity are mediated by gamma interferon (IFN-gamma) and are based on a differential activation of the innate immune mechanisms which recognize and react against the LPS present in infecting bacteria . In P . acnes-primed mice null for LPS-binding protein (LBP(-/-) mice), the impaired LPS recognition, due to the absence of LBP, resulted in a higher resistance to serovar Typhimurium infection . A similar P . acnes priming of mice had a protective, but no deleterious effect on a subsequent L . monocytogenes infection . This effect was IFN-gamma dependent but independent of LBP.

J Dermatolog Treat, 2002 Sep, 13(3), 107 - 10
Comparative efficacy of clindamycin and benzoyl peroxide for in vivo suppression of Propionibacterium acnes; Gans EH et al.; BACKGROUND: Benzoyl peroxide and clindamycin are the two most widely prescribed topical antimicrobials in the treatment of acne . AIM: To compare the antimicrobial efficacy, in vivo, of benzoyl peroxide and clindamycin against Propionibacterium acnes . METHODS: Two groups of 10 subjects each, with comparable mean P . acnes baseline counts of log 5.75 to 5.85, underwent twice daily application of benzoyl peroxide or clindamycin for 14 days . RESULTS: The results of quantitatively sampling P . acnes after 3, 7 and 14 days of treatment showed that Triaz 6% benzoyl peroxide special gel produced faster and significantly greater reductions in P . acnes than did the 1% clindamycin phosphate in Cleocin-T lotion (p < 0.01) . These results were paralleled by the greater reductions produced by Triaz versus Cleocin (p < 0.05) in P . acnes fluorescence . CONCLUSION: Benzoyl peroxide formulations suppress the follicular population of P . acnes more rapidly and to a greater degree than topical antibiotics such as clindamycin.

Skin Therapy Lett, 2002 May, 7(5), 3 - 7
Systemic antibiotic therapy for acne: a review; Kunynetz R; Acne is a multifactorial disease of the pilosebaceous unit in the skin . Four contributing pathogenic factors need to be elucidated and include excess sebum production, follicular hyperkeratinization, colonization of the pilosebaceous unit by Propionibacterium acnes, which is a gram positive anaerobic diphtheroid, and the release of inflammatory mediators into the follicle and dermis . One or more of these factors are targeted by each of the systemic therapies for this disease and its variant, including systemic antibiotic therapies, which will be reviewed here.

Ann Dermatol Venereol, 2002 Jun-Jul, 129(6-7), 874 - 82
{Doxycycline}; Bonnetblanc JM; Doxycyclin is a semi-synthetic structural isomer of the tetracycline family . It exhibits good intra-cellular penetration, with bacteriostatic activity on many bacteria . Different types or bacterial resistance are known . Acquired resistance has a ribosomal or a plasmidic mechanism . Resistance of Propionibacterium acnes is secondary to a mutation of ARNr . Doxycyclin also has an anti-inflammatory activity, via numerous pathways . Doxycyclin is rapidly and almost completely absorbed by the digestive tract . Food has no incidence on the absorption . It has a high but labile affinity for proteins with 90 p . 100 of the molecule linked . It rapidly diffuses in the extravascular compartment and in most of the tissues . Bile excretion is the main excretion route . It occurs more slowly by the kidney with tubular reabsorption . The main dermatological indication is acne with daily dose varing between 50 mg and 100 mg . Although good assays are lacking, a large professional consensus has validated its use . It is also active at the same dosage in rosacea . Chlamydial and mycoplasma urethritis may be treated by doxycyclin, and this antibiotic is presently used as second choice . Many other diseases may be treated as a primary or secondary choice, such as treponematoses, brucellosis, pasteurellosis, borreliosis, rickettsioses and cholera . Some non infectious diseases have been occasionally treated by doxycycline . Digestive side effects are the more frequent . Esophageal toxicity has been reduced with tablets and sufficient concomitant water ingestion . Phototoxicity is dose-dependent . Various cutaneous side effects have been described, some of them severe . Systemic toxicity is rare . Pregnancy is a contra-indication, and as other tetracyclines, it should not be given to children and during lactation . Doxycycline is commercialized as tablets . No reduction of the dose is necessary in renal failure . Association with retinoids is not recommended . Anticoagulants are potentialized . Didanosin, iron, and mineral salts lower its activity.

J Dairy Sci, 2002 Jul, 85(7), 1738 - 51
Propionibacteria fed to dairy cows: effects on energy balance, plasma metabolites and hormones, and reproduction; Francisco CC et al.; To determine the effect of feeding Propionibacteria on energy balance, milk yield, and composition, metabolites and hormones of early-lactating dairy cows, multiparous Holstein cows were individually fed a total mixed ration from -2 to 12 wk postpartum with no addition (control, n = 10) or with an additional 17 g of Propionibacteria culture daily (Treated, n = 9) . Daily feed intake and milk production were recorded . Plasma cholesterol, nonesterified fatty acids (NEFA), leptin, insulin, glucose, insulin-like growth factor-I (IGF-I), IGF-binding proteins (IGFBP), and progesterone concentrations were measured up to twice weekly . Cows fed supplemental Propionibacteria had improved energy balance at wk 1 of lactation and had lower DMI per kg of body weight than control cows on wk 3 to 7, 10, and 12 . Cows fed Propionibacteria had a greater percentage of milk protein and solids-not-fat and plasma NEFA concentrations than did control cows only at wk 1 of lactation . Treatment did not affect milk production or percentage of milk fat and lactose . Leptin levels were greater in treated than control cows throughout the study . Plasma glucose, insulin, cholesterol, IGFBP-3, and IGF-I concentrations were not affected by feeding Propionibacteria, but those variables increased with week postpartum . Plasma IGFBP-2 and IGFBP-5 levels decreased with week postpartum . Measures of reproductive and ovarian function did not differ between Propionibacteria-treated and control cows . Feeding Propionibacteria culture to transition and early lactating dairy cows may hold potential for improved milk protein production and metabolic efficiency during early lactation, without affecting reproductive function.

Clin Ther, 2002 Jul, 24(7), 1117 - 33
A randomized, double-blind comparison of a clindamycin phosphate/benzoyl peroxide gel formulation and a matching clindamycin gel with respect to microbiologic activity and clinical efficacy in the topical treatment of acne vulgaris; Cunliffe WJ et al.; BACKGROUND: One approach to suppressing the overgrowth of antibiotic-resistant bacteria is to develop combination products composed of active constituents with complementary but distinct mechanisms of antibacterial action . OBJECTIVE: The purpose of this study was to compare the antimicrobial and clinical efficacy and tolerability of clindamycin phosphate 1%/benzoyl peroxide 5% gel formulation with matching clindamycin 1% gel in the treatment of acne vulgaris . METHODS: This 16-week, single-center, double-blind, randomized, parallel-group study compared the combination gel with clindamycin monotherapy applied BID in patients 13 to 30 years of age with mild to moderate acne and facial Propionibacterium acnes counts > or = 10(4) colony-forming units per square centimeter of skin . RESULTS: Seventy-nine patients were enrolled and randomly assigned to receive the combination gel (n = 40) or clindamycin monotherapy (n = 39) . Seventy patients (50 males, 20 females; mean age, 18.2 years) were included in the intent-to-treat group . The combination gel treatment produced significantly greater reductions (P < or = 0.046) from baseline in total lesion counts and in numbers of inflammatory lesions and comedones compared with clindamycin monotherapy . Greater reductions in the severity of acne also were observed in the physician's and patient's Clinical Global Improvement scale scores and in other secondary efficacy measurements . Reductions in clindamycin-resistant P acnes counts were observed relative to baseline in the combination gel group; in contrast, P acnes counts increased by >1,600% in the clindamycin monotherapy group at week 16 (P = 0.018 vs combination gel) . Reductions in inflammatory (r2 = 0.31; P = 0.016) and total (r2 = 0.28; P = 0.027) lesions were correlated with decreases in clindamycin-resistant bacteria . Also, significant correlations were observed between the percent change from baseline in total lesion counts (r2 = 0.44; P < 0.001) and comedo counts (r2 = 0.50; P < 0.001) and the log10 change from baseline in total P acnes counts . CONCLUSIONS: The total P acnes count (P = 0.002) and the clindamycin-resistant P acnes count (P = 0.018) were significantly reduced after 16 weeks of treatment with combination gel compared with clindamycin monotherapy . These reductions in total P acnes and clindamycin-resistant P acnes counts correlated with reductions in total acne lesions.

Curr Opin Pulm Med, 2002 Sep, 8(5), 429 - 34
What causes sarcoidosis?
Moller DR, Chen ES.
Limited but encouraging progress has been made over the last several years in our understanding of the etiology of sarcoidosis as a result of recent investments in epidemiologic, immunologic, and molecular biologic studies . A recent US multicenter study of sarcoidosis found few environmental or occupational exposures associated with a two-fold or higher risk of development of sarcoidosis, suggesting noninfectious exposures play a small, if any, role in causing systemic sarcoidosis . In contrast, recent studies have linked infectious agents including mycobacterial and propionibacterial organisms with sarcoidosis . The association of sarcoidosis with the use of Th1-promoting biologic response modifiers is consistent with a central role for enhanced Th1 immune responses in the pathogenesis of sarcoidosis . Given evidence for a genetic predisposition to sarcoidosis, these findings suggest that the etiology of systemic sarcoidosis is linked to genetically determined enhanced Th1 immune responses to a limited number of microbial pathogens.

J Clin Microbiol, 2002 Aug, 40(8), 3060 - 3
Assessment of mycobacterial, propionibacterial, and human herpesvirus 8 DNA in tissues of greek patients with sarcoidosis; Gazouli M et al.; The causes of sarcoidosis are unknown . In this study, we report the presence of Mycobacterium tuberculosis complex and Propionibacterium granulosum DNA in a significant proportion of Greek patients with sarcoidosis . Human herpesvirus 8 DNA was not detected in sarcoid tissues from Greek patients . Our findings are discussed.

No Shinkei Geka, 2002 Jul, 30(7), 731 - 3
{Postoperative subdural empyema due to Propionibacterium acnes}; Uozumi Y et al.; Propionibacterium acnes are gram-positive pleomorphic rods that grow under an anaerobic condition . They are the most frequent inhabitants of sebaceous glands of skin, hair follicles, mouth, upper respiratory tract, and as a frequent contaminant in laboratory cultures . Propionibacterium acnes is an underestimated but significant cause of postneurosurgical infection, especially in the presence of foreign bodies such as shunt systems . We present a rare case with a postoperative subdural empyema in which the only pathogen isolated was Propionibacterium acnes . In our case, the clinical course was atypically rapid . The most effective antibiotic therapy for Propionibacterium acnes infections has not been established . However, high dose penicillin in combination with surgical drainage and removal of foreign bodies is recommended as the treatment of choice.

J Immunol, 2002 Aug 1, 169(3), 1535 - 41
Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses; Kim J et al.; One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P . acnes induces inflammation is not known . Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs) . We investigated whether TLR2 mediates P . acnes-induced cytokine production in acne . Transfection of TLR2 into a nonresponsive cell line was sufficient for NF-kappa B activation in response to P . acnes . In addition, peritoneal macrophages from wild-type, TLR6 knockout, and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P . acnes . P . acnes also induced activation of IL-12 p40 promoter activity via TLR2 . Furthermore, P . acnes induced IL-12 and IL-8 protein production by primary human monocytes and this cytokine production was inhibited by anti-TLR2 blocking Ab . Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles . These data suggest that P . acnes triggers inflammatory cytokine responses in acne by activation of TLR2 . As such, TLR2 may provide a novel target for treatment of this common skin disease.

Can J Microbiol, 2002 May, 48(5), 449 - 57
Some factors affecting the adherence of probiotic Propionibacterium acidipropionici CRL 1198 to intestinal epithelial cells; Zarate G et al.; Adhesion to the intestinal mucosa is generally considered an important property of probiotic microorganisms and has been related to many of their health benefits . This study investigated some factors that could affect or be involved in the adherence of Propionibacterium acidipropionici CRL 1198, a dairy strain with suggested probiotic effects and high adherence in vitro and in vivo to intestinal epithelial cells . In vitro adhesion of propionibacteria was decreased by gastric digestion but not affected by bile and pancreatic enzymes . Adherence was also decreased by pretreatment of bacterial cells with protease, sodium metaperiodate, and trichloroacetic acid, revealing that different features of the cell surface, like protein factors, carbohydrates, and teichoic acids, are involved in the process . Adherence to intestinal epithelial cells was enhanced by calcium and was dependent on other divalent cations . Adhesion to intestinal mucus was also demonstrated . The results should explain the metabolic effects in the host previously obtained with this strain and support the potential of Propionibacterium for development of new probiotics.

J Gastroenterol, 2002, 37 Suppl 13, 74 - 7
Indications and criteria for liver transplantation for fulminant hepatic failure; Fujiwara K et al.; Liver transplantation is the only effective treatment for potentially fatal cases of fulminant hepatic failure . However, it is very difficult to predict which cases will be fatal . The mortality may depend on alternative medical therapies . According to a nationwide survey of patients with fulminant hepatic failure presenting with encephalopathy of a coma grade greater than II within 8 weeks from the first symptoms of illness with a prothrombin time less than 40% of normal value, there were 93 patients in 311 hospitals between January and December 1998 in Japan . During this period, there were 11 patients with late-onset hepatic failure . The etiology was HAV infection in 4%, HBV infection in 44%, and nonA-nonB in 41% . Specific therapies were intensively used in all patients . The mean survival rate was 41%, with differences depending on the etiology . Six patients underwent liver transplantation, and 5 survived . In animal experiments, sinusoidal fibrin deposition caused massive liver necrosis . Activation of Kupffer cells and hepatic macrophages was a major contributing factor of this development . There were different mechanisms of such fibrin deposition . Tumor necrosis factor-alpha and superoxide anions released from hepatic macrophages after endotoxin administration destroyed endothelial cells, and then coagulopathy occurred in the sinusoids in rats given Propionibacteriom acnes, while a tissue factor from Kupffer cells played that role in rats undergoing partial hepatectomy . The prognosis of fulminant hepatic failure may depend on the etiology . The indication for liver transplantation for this disease must be carefully decided by analyzing the etiology, pathological conditions, and response to therapies in each case.

J Dermatol Sci, 2002 Aug, 29(2), 97 - 103
Propionibacterium acnes-induced IL-8 production may be mediated by NF-kappaB activation in human monocytes; Chen Q et al.; Propionibacterium acnes (P . acnes) causes an inflammatory acne that is characterized by massive neutrophilic infiltration . IL-8 is thought to play an important role in the pathophysiology of P . acnes, although the mechanisms by which P . acnes up-regulates the release of IL-8, a neutrophilic chemokine, from target cells is not well understood . In this study, we investigated the mechanisms through which heat-killed P . acnes induces IL-8 production in THP-1 cells (a human monocytic cell line) . We found that P . acnes is able to directly induce IL-8 production and IL-8 mRNA expression in human monocytic cells in a dose- and time-dependent manner through a mechanism requiring transcription factor NF-kappaB activation . Additionally, P . acnes-induced IL-8 secretion was inhibited by roxithromycin, a macrolide antibiotic, and its inhibitory effect seemed to be partially associated with the inhibition of P . acnes-induced NF-kappaB activation . This is the first study to show that NF-kappaB activation is involved in the IL-8 production of monocytic cells stimulated by P . acnes.

Cutis, 2002 Jun, 69(6), 475 - 80
Effect of topical benzoyl peroxide/clindamycin versus topical clindamycin and vehicle in the reduction of Propionibacterium acnes; Leyden JJ; Propionibacterium acnes is one of the primary factors involved in the pathogenesis of acne vulgaris; proliferation of this bacteria is present in all patients with inflammatory lesions . Combination topical therapy with agents that have different but complementary antimicrobial mechanisms of action has the potential to increase efficacy and to prevent the emergence of resistant organisms . The onset of action and effectiveness of 3 topical preparations (benzoyl peroxide 5%/clindamycin phosphate 1% gel, clindamycin phosphate 1% solution, and vehicle gel) in reducing P acnes were compared in a randomized, open-label, evaluator-blinded, comparative trial involving 60 healthy volunteers who were free of acne but had high levels of facial P acnes . Treatment with benzoyl peroxide 5%/clindamycin phosphate 1% gel significantly (P<.001) reduced P acnes levels by >1 log10/cm2 from baseline (91% inhibition) 24 hours after application . Progressive declines were observed throughout the 2-week study period, with a 3 log10/cm2 reduction (99.9% inhibition) from baseline in P acnes at the end of the 2-week treatment period . In contrast, significant (P<.05) reductions from baseline in P acnes levels following treatment with clindamycin phosphate 1% solution were only observed at the last assessment period (2 weeks), with an average reduction of 0.64 log10/cm2 (77% inhibition) . Patients receiving vehicle gel had no measurable reductions in P acnes from baseline . These results demonstrate that topical benzoyl peroxide 5%/clindamycin phosphate 1% gel produces rapid and clinically relevant reductions in P acnes greater than those produced by single-agent therapy . This activity is likely responsible for the quick onset of clinical efficacy produced by this combination regimen.

Dermatology, 2002, 204(4), 277 - 80
Effects of Roxithromycin on the production of lipase and neutrophil chemotactic factor by Propionibacterium acnes; Akamatsu H et al.; BACKGROUND: The macrolide antibiotic roxithromycin is effective against acne associated with inflammation, but the mechanism by which this is achieved has not been clarified . OBJECTIVE: We studied the effects of roxithromycin on the production of lipase and neutrophil chemotactic factor by Propionibacterium acnes in vitro . RESULTS: Roxithromycin significantly inhibited the production of lipase and neutrophil chemotactic factor by P . acnes at a concentration one eighth of the MIC, at which the growth curve of P . acnes is not affected . CONCLUSION: One mechanism of the effectiveness of roxithromycin in acne therapy is thought to be the inhibition of bacterial lipase and neutrophil chemotactic factor production by P . acnes .

Am J Clin Dermatol, 2002, 3(5), 349 - 60
Clindamycin/benzoyl peroxide gel: a review of its use in the management of acne; Warner GT et al.; Clindamycin/benzoyl peroxide gel has demonstrated clinical efficacy in the treatment of acne vulgaris through both antibacterial and anti-inflammatory means . Benzoyl peroxide may exert its antibacterial activity by the interaction of oxidized intermediates with elements of bacterial cells . Clindamycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunits causing inhibition of peptide-bond formation . Benzoyl peroxide decreases inflammatory damage by inhibiting the release of reactive oxygen species from polymorphonuclear leukocytes (PMNs) through the killing of PMNs . Clindamycin suppresses the complement-derived chemotaxis of polymorphonuclear leukocytes in vitro, thereby reducing the potential for inflammation . Several well designed clinical trials have demonstrated that twice-daily application of clindamycin 1%/benzoyl peroxide 5% gel for 10 to 16 weeks was more effective in reducing the number of inflammatory lesions than benzoyl peroxide 5%, clindamycin 1% or vehicle in patients with mild to moderately severe acne . Two studies also showed clindamycin/benzoyl peroxide to be more effective than benzoyl peroxide, clindamycin or vehicle in reducing total lesions, and one study showed clindamycin/benzoyl peroxide to be significantly more efficacious than clindamycin or vehicle in reducing the number of noninflammatory lesions . Moreover, in two trials, physician-rated mean global improvement scores, as well as patient-rated scores in one of those trials, were significantly greater in the clindamycin/benzoyl peroxide group than in the benzoyl peroxide, clindamycin or vehicle groups . In another study, clindamycin/benzoyl peroxide was as efficacious as benzoyl peroxide/erythromycin in the reduction of inflammatory and noninflammatory lesions and in raising mean global improvement scores, but was significantly more effective than benzoyl peroxide in the reduction of inflammatory lesions and in increasing both physician- and patient-assessed global improvement scores . Clindamycin/benzoyl peroxide gel applied twice daily was well tolerated in clinical trials in patients with acne, and has a tolerability profile similar to that of benzoyl peroxide alone . The most common adverse events were dry skin, peeling, erythema and rash; however, adverse event-caused treatment discontinuation rates for patients using clindamycin/benzoyl peroxide were low, ranging from 0 to 0.8% . CONCLUSIONS: Clindamycin/benzoyl peroxide gel has demonstrated efficacy and good overall tolerability in several well designed clinical studies in the topical treatment of patients with mild to moderately severe acne vulgaris . Clindamycin/benzoyl peroxide was more effective than benzoyl peroxide, clindamycin or vehicle, and similar in efficacy to benzoyl peroxide/erythromycin in the reduction of inflammatory lesions and in raising physician- and patient-assessed mean global improvement scores . It may be useful in treating patients with acne caused by resistant strains of Propionibacterium acnes . Clindamycin/benzoyl peroxide gel is an effective topical agent in the treatment of patients with mild to moderately severe acne . It is a suitable alternative for patients who are currently using topical antibacterials either alone or in conjunction with other topical anti-acne agents or systemic antibacterials.

Microbiology, 2002 Jun, 148(Pt 6), 1845 - 53
Isolation and characterization of 14 additional genes specifying the anaerobic biosynthesis of cobalamin (vitamin B12) in Propionibacterium freudenreichii (P . shermanii); Roessner CA et al.; A search for genes encoding enzymes involved in cobalamin (vitamin B12) production in the commercially important organism Propionibacterium freudenreichii (P . shermanii) has resulted in the isolation of an additional 14 genes encoding enzymes responsible for 17 steps of the anaerobic B12 pathway in this organism . All of the genes believed to be necessary for the biosynthesis of adenosylcobinamide from uroporphyrinogen III have now been isolated except two (cbiA and an as yet unidentified gene encoding cobalt reductase) . Most of the genes are contained in two divergent operons, one of which, in turn, is closely linked to the operon encoding the B12-dependent enzyme methylmalonyl-CoA mutase . The close linkage of the three genes encoding the subunits of transcarboxylase to the hemYHBXRL gene cluster is reported . The functions of the P . freudenreichii B12 pathway genes are discussed, and a mechanism for the regulation of cobalamin and propionic acid production by oxygen in this organism is proposed.

Rev Prat, 2002 Apr 15, 52(8), 841 - 3
{General antibiotic therapy in acne}; Dreno B; The primary indication for systemic antibiotics is acute therapy for moderate-to-severe inflammatory acne . The preferred agents include tetracyclines and derivatives; macrolides, co-trimoxazole, and trimethoprim may represent acceptable alternatives . Antibiotics act mainly on inflammatory lesions (papules and pustules) and are only slightly comedolytic . Oral antibiotics reduce the number of Propionibacterium acnes . In addition, they have an anti-inflammatory activity . The side effects associated with oral antibiotics for acne depend on the drug; however, severe side effects are not common . Resistant strains of Propionibacterium acnes to antibiotics are increasing . Thus, general guidelines are useful when utilizing oral antibiotic therapy in acne.

Rev Prat, 2002 Apr 15, 52(8), 828 - 30
{Mechanisms and causes of acne}; Beylot C; Three pathogenic factors are closely involved in the mechanism of acne with a sequence beginning with seborrhea, then sebum retention, and finally inflammation . The sebaceous gland is a target of androgens . Acne may be related to an excessive sensitivity of sebaceous end-organs to androgens . However, in women, an ovarian or adrenal hyperandrogenism may be implicated . The cause of sebum retention is the hyperkeratinisation of the infra infundibulum of the sebaceous duct . Many factors, particularly the chemical composition of sebum in acne and the androgens are responsible for this hyperkeratinisation . The inflammation is related to the inflammatory role of the numerous enzymes of Propionibacterium acnes and to the chimiotactism of neutrophils . Other pathogenic factors may have a role in acne, particularly smoking and stress . The knowledge of these pathogenic factors and their evaluation in each patient are a main point for therapeutic strategy, because every available treatment has a special impact on such or such factor.

J Immunol, 2002 Jun 1, 168(11), 5621 - 8
Induction of macrophage-inflammatory protein-3alpha gene expression by TNF-dependent NF-kappaB activation; Sugita S et al.; Macrophage-inflammatory protein-3alpha (MIP-3alpha), also designated as liver and activation-regulated chemokine (LARC), Exodus, or CCL20, is a recently identified CC chemokine that is expected to play a crucial role in the initiation of immune responses . In this study, we describe that MIP-3alpha expression is under the direct control of NF-kappaB, a key transcription factor of immune and inflammatory responses . Overexpression of the p65/RelA subunit of NF-kappaB significantly increased the MIP-3alpha mRNA level . MIP-3alpha transcription was stimulated by TNF, and this stimulation was inhibited by an NF-kappaB inhibitor, I-kappaBalpha superrepressor . Analysis of the human MIP-3alpha promoter demonstrated a functional NF-kappaB site responsible for its expression . We also show that MIP-3alpha expression is induced in LPS-treated mouse livers that were primed with Propionibacterium acnes, which developed massive liver injury with infiltration of inflammatory cells . This induction was fully dependent on the TNF signaling cascade, because it was not observed in the livers of TNFR1-deficient mice . Furthermore, pretreatment with gliotoxin, an inhibitor of NF-kappaB activity, abrogated the P . acnes/LPS-induced MIP-3alpha expression of wild-type mice . These results clearly demonstrate that MIP-3alpha gene expression is dependent on NF-kappaB activity in vitro, and indicate that the TNFR1-mediated TNF signaling cascade that leads to NF-kappaB activation plays an essential role in MIP-3alpha expression in the murine liver injury model.

J Exp Med, 2002 May 20, 195(10), 1257 - 66
Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes; Yoneyama H et al.; Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets . Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored . Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs) . Hepatic LN DCs preferentially produced CXCL10 to attract 5'-bromo-2'-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-gamma-producing CD4+ T cells by day 7 after antigen challenge . Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells . BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody . This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-gamma leading to exacerbation of liver injury . Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses.

New Microbiol, 2002 Apr, 25(2), 239 - 42
Perianal abscess caused by Propionibacterium avidum in a cirrhotic patient; Wang TK et al.; We describe the first case of community-acquired Propionibacterium avidum subcutaneous tissue infection in a cirrhotic patient . A 70-year-old Chinese male with a 2-year history of hepatitis B virus-induced chronic liver failure and hemorrhoidectomy 17 months previously presented with a painful left buttock abscess, which was culture positive for P . avidum . Being a normal flora of skin with low pathogenicity, there have been only 3 case reports on P . avidum infection, all associated with surgical intervention within 2 to 6 weeks before the onset of P . avidum infection . We hereby review the literature on P . avidum summarizing

Br J Dermatol, 2002 May, 146(5), 840 - 8
Prevalence of antibiotic-resistant propionibacteria on the skin of acne patients: 10-year surveillance data and snapshot distribution study; Coates P et al.; BACKGROUND: Cutaneous propionibacteria are implicated in acne pathogenesis, although their exact role in the genesis of inflammation is still poorly understood . Agents, including antibiotics, that reduce the numbers of propionibacteria on skin are therapeutic . Resistance in the target organism is a well-recognized consequence of antibiotic therapy for acne but formal prevalence and distribution data are lacking . OBJECTIVES: To monitor the prevalence of skin colonization by antibiotic-resistant propionibacteria in acne patients attending the dermatology out-patient clinic at Leeds General Infirmary over a 10-year period beginning in 1991, and to examine the distribution of resistant strains on acne-prone skin and in the nares . METHODS: Propionibacterial samples were obtained from the skin surface of the worst affected site (usually the face) of 4274 acne patients using a moistened swab . The swab was used to inoculate agar plates with and without selective antibiotics . After anaerobic incubation at 37 degrees C for 7 days, the amount of growth in the presence of each antibiotic was scored on a scale from 0 to 5+ . A small number of patients (72) were selected for more detailed quantitative sampling at six different sites to examine the distribution of resistant propionibacteria on acne-prone skin and in the anterior nares . RESULTS: The proportion of patients carrying strains resistant to one or more commonly used antiacne antibiotics rose steadily from 34.5% in 1991 to a peak of 64% in 1997 . The prevalence dropped to 50.5% during 1999 and then rose again to 55.5% in 2000 . Resistance to erythromycin was the most common and the majority of erythromycin-resistant strains were cross-resistant to clindamycin . Resistance to tetracyclines was less common in all years and with little increase over time . The more detailed quantitative study in 72 patients showed that population densities of resistant propionibacteria varied considerably between sites and between individuals . Almost invariably, patients were colonized with resistant strains at multiple sites, including the nares . CONCLUSIONS: Skin colonization with antibiotic-resistant propionibacteria is much more common now than a decade ago . Resistant propionibacteria are widely distributed on acne-prone skin and in the nares . This suggests that they will be very difficult to eradicate using existing therapeutic regimens, especially from the nasal reservoir.

Biochemistry, 2002 Apr 23, 41(16), 5193 - 201
Metabolic engineering of a methylmalonyl-CoA mutase-epimerase pathway for complex polyketide biosynthesis in Escherichia coli; Dayem LC et al.; A barrier to heterologous production of complex polyketides in Escherichia coli is the lack of (2S)-methylmalonyl-CoA, a common extender substrate for the biosynthesis of complex polyketides by modular polyketide synthases . One biosynthetic route to (2S)-methylmalonyl-CoA involves the sequential actions of two enzymes, methylmalonyl-CoA mutase and methylmalonyl-CoA epimerase, which convert succinyl-CoA to (2R)- and then to (2S)-methylmalonyl-CoA . As reported {McKie, N., et al . (1990) Biochem . J . 269, 293-298; Haller, T., et al . (2000) Biochemistry 39, 4622-4629}, when genes encoding coenzyme B(12)-dependent methylmalonyl-CoA mutases were expressed in E . coli, the inactive apo-enzyme was produced . However, when cells harboring the mutase genes from Propionibacterium shermanii or E . coli were treated with the B12 precursor hydroxocobalamin, active holo-enzyme was isolated, and (2R)-methylmalonyl-CoA represented approximately 10% of the intracellular CoA pool . When the E . coli BAP1 cell line {Pfeifer, B . A., et al . (2001) Science 291, 1790-1792} harboring plasmids that expressed P . shermanii methylmalonyl-CoA mutase, Streptomyces coelicolor methylmalonyl-CoA epimerase, and the polyketide synthase DEBS (6-deoxyerythronolide B synthase) was fed propionate and hydroxocobalamin, the polyketide 6-deoxyerythronolide B (6-dEB) was produced . Isotopic labeling studies using {(13)C}propionate showed that the starter unit for polyketide synthesis was derived exclusively from exogenous propionate, while the extender units stemmed from methylmalonyl-CoA via the mutase-epimerase pathway . Thus, the introduction of an engineered mutase-epimerase pathway in E . coli enabled the uncoupling of carbon sources used to produce starter and extender units of polyketides.

Drugs Exp Clin Res, 2001, 27(5-6), 161 - 4
Effect of lipase activities of Propionibacterium granulosum and Propionibacterium acnes; Higaki S et al.; We studied the lipase activities of Propionibacterium granulosum, P . acnes and the suppression of these activities by Jumi-haidoku-to (JHT) . Lipase activity of P . acnes biotype III (BIII) was strongest, while that of P . granulosum was faintly expressed . Compared with the control medium, the production of propionic and butyric acids was suppressed by all the tested mediums combined with JHT . The decrease in these acids produced by JHT was significantly higher in P . granulosum than in P . acnes . Although P . acnes BIII may produce a strong effect on acne, the presence of P . granulosum should not be ignored . Further research is required on the correlation between P . acnes and P . granulosum.

Int J Syst Evol Microbiol, 2002 Mar, 52(Pt 2), 441 - 4
Propionivibrio limicola sp . nov., a fermentative bacterium specialized in the degradation of hydroaromatic compounds, reclassification of Propionibacter pelophilus as Propionivibrio pelophilus comb . nov . and amended description of the genus Propionivibrio; Brune A et al.; Strain GolChi1T, a mesophilic, anaerobic bacterium, was isolated with quinic acid (1,3,4,5-tetrahydroxy-cyclohexane-1-carboxylic acid) as the sole source of carbon and energy . Of more than 30 substrates tested, only the hydroaromatic compounds quinic acid and shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) were utilized, yielding acetate and propionate as the only fermentation products . Sugars, alcohols, (di-)carboxylic acids, amino acids and aromatic compounds were not fermented and no external electron acceptors were used . Strain GolChi1T is a gram-negative, rod-shaped, aerotolerant anaerobe that possesses superoxide dismutase; it does not employ the classical hydroaromatic pathway of aerobic bacteria for the degradation of hydroaromatic compounds (no aromatic intermediates involved) . 16S-rRNA-based phylogenetic analyses revealed a common origin of this isolate and Rhodocyclus, Propionibacter and Propionivibrio species . High sequence similarity (> 96%) and phenotypic traits indicated a closer relationship between strain GolChi1T and the type species of the monospecific genera Propionivibrio and Propionibacter but, due to its phenotypic properties, strain GolChi1T could not be assigned conclusively to either of these taxa . We propose (i) the amended description of the genus Propionivibrio, (ii) the reclassification of Propionibacter pelophilus Meijer et al . 1999 as Propionivibrio pelophilus comb . nov . and (iii) designation of Propionivibrio limicola sp . nov., with the type strain GolChi1T (= DSM 6832T = ATCC BAA-290T).

Hepatology, 2002 Apr, 35(4), 805 - 14
The resistance of P . acnes--primed interferon gamma-deficient mice to low-dose lipopolysaccharide-induced acute liver injury; Shimizu Y et al.; Endotoxin has been identified as a principal mediator of sepsis, often with resulting multiple organ failure . Although interferon gamma (IFN-gamma) has a central role in controlling bacterial infection through the activation of macrophages and T lymphocytes, it can also enhance the harmful effects of the inflammatory response . To examine the role of IFN-gamma in lipopolysaccharide (LPS)-induced injury, we administered LPS (20 or 800 microg/mouse) alone or as low-dose LPS (20 microg/mouse) 7 days after heat-killed Propionibacterium acnes (P . acnes) injection into wild-type C57BL/6 (B6) mice or IFN-gamma-deficient (GKO) mice (B6 background) . Although low-dose (20 microg) LPS alone had no effect on survival, the administration of 800 microg LPS alone resulted in 100% mortality in both B6 and GKO mice without significant hepatic mononuclear cellular infiltration or differences in elevated plasma tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-12 levels . In contrast, mortality after low-dose (20 microg) LPS challenge in P . acnes-primed B6 mice was 100%, but 0% in GKO mice . In vivo plasma cytokine (IFN-gamma, TNF-alpha, IL-6, and IL-12) levels and in vitro cytokine production by hepatic mononuclear cells were significantly higher in B6 mice compared with GKO mice . Associated hepatic mononuclear cellular infiltration, multifocal liver necrosis, hepatomegaly, and splenomegaly were found in B6 mice, but not in GKO mice . Finally, the anti-inflammatory NK1.1+CD4+ cell proportion of hepatic infiltrating mononuclear cell numbers 7 days after P . acnes administration was significantly reduced in B6 compared with GKO mice, whereas the proportion of inflammatory NK1.1+CD4- cells was increased . In conclusion, these data suggest that IFN-gamma mediates P . acnes-primed low-dose LPS injury through the hepatic infiltration of mononuclear cells and the subsequent elevation of inflammatory cytokines after LPS challenge, whereas the lethal effects of high-dose LPS alone does not depend on the presence of IFN-gamma.

Liver, 2001 Dec, 21(6), 415 - 24
Sinusoidal endothelial cell injury by superoxide anion and iron in the Propionibacterium acnes-pretreated and lipopolysaccharide-stimulated rat liver; Hasegawa T et al.; AIMS/BACKGROUND: We attempted to measure the generation of superoxide anion, examine its site of release and determine its pathological role in Propionibacterium acnes-lipopolysaccharide-induced liver injury in the rat . METHODS: The P . acnes-pretreated (16 mg/kg i.v.) rat liver was perfused with buffer containing lipopolysaccharide (2.5 microg/ml) . Chemiluminescence enhanced with Cypridina luciferin analog, MCLA, and reduction of nitro blue tetrazolium were used for detecting superoxide anion . Leakage of enzymes and release of cytokines into the perfusate, and histological specimens were also examined . RESULTS: Superoxide dismutase-inhibitable chemiluminescence peaked at 30 min of lipopolysaccharide infusion and blue formazan precipitate was histochemically deposited mainly on hepatic macrophages . Purine nucleoside phosphorylase (PNP) activity in the perfusate, as a marker of sinusoidal endothelial cell injury, reached its maximum at 50 min and aspartate aminotransferase (AST) activity, as a marker of hepatocyte injury, reached a plateau at 90 min . Simultaneous treatment with superoxide dismutase and deferoxamine mesylate significantly suppressed the leakage of PNP and AST . Release of tumor necrosis factor-alpha and growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 lagged behind PNP leakage . Light microscopy showed destruction of the sinusoids followed by hepatocyte necrosis . Electron microscopy revealed adherence of hepatic macrophages to sinusoidal endothelial cells . CONCLUSION: These results indicate that superoxide anion released from hepatic macrophages may induce sinusoidal endothelial cell injury via interaction with iron in the P . acnes-lipopolysaccharide-treated liver.

Br J Dermatol, 2002 Feb, 146(2), 202 - 9
Propionibacterium acnes and inflammation in acne; P . acnes has T-cell mitogenic activity; Jappe U et al.; BACKGROUND: Circumstantial evidence suggests that Propionibacterium acnes has a role in the inflammation of acne . This could be effected by antigenic or superantigenic or mitogenic reactions . OBJECTIVES: The purpose of this investigation was to determine whether P . acnes had only antigenic activity or additional superantigenic and mitogenic activity . METHODS: A lymphocyte transformation assay was used to detect responses to a mixture of eight P . acnes whole cell isolates, and their supernatant culture fluids . In order to determine the nature of T-cell reactions to P . acnes cells a mouse-antihuman major histocompatibility complex class II monoclonal antibody was used in the lymphocyte transformation assay to inhibit the antigenic stimulation of lymphocytes . An analysis of the T-cell receptor (TCR) variable region beta (BV) repertoire was undertaken using flow cytometry of the unstimulated and stimulated cells . RESULTS: Peripheral blood mononuclear cells (PBMNC) from adults with no history of acne responded strongly to stationary growth phase cells of P . acnes, less strongly to cells in the exponential growth phase . No response was detected to supernatant culture fluids . PBMNC from five cord blood samples (CBMNC) responded maximally after 3 and 7 days of incubation with stationary growth phase cells of P . acnes . The reaction of CBMNC to P . acnes cells was not suppressed completely by the blocking antibody . The analysis of the TCRBV repertoire indicated that P . acnes induced no deletion or over-representation of certain BV element-bearing T cells . The TCRBV analysis was repeated after preincubation with the blocking antibody . Deletion of T cells bearing certain BV components occurred and there was no over-representation of T cells carrying certain BV components . CONCLUSIONS: Two mechanisms of lymphocyte activation by P . acnes cells are proposed, antigen and mitogen driven . These results are consistent with the histological evidence of inflammation in acne lesions.

J Food Prot, 2002 Mar, 65(3), 534 - 9
Adhesion of dairy propionibacteria to intestinal epithelial tissue in vitro and in vivo; Zarate G et al.; Adhesion to the intestinal mucosa is a desirable property for probiotic microorganisms and has been related to many of their health benefits . In the present study, 24 dairy Propionibacterium strains were assessed with regard to their hydrophobic characteristics and their autoaggregation and hemagglutination abilities, since these traits have been shown to be indicative of adherence in other microorganisms . Six strains were further tested for their capacity to adhere to ileal epithelial cells in vitro and in vivo . The results of the study showed that propionibacteria were highly hydrophilic, and hemagglutination and autoaggregation were properties not commonly found among these microorganisms . No relationship was found between surface characteristics and adhesion ability, since hemagglutinating, autoaggregating, and nonautoaggregating bacteria were able to adhere to intestinal cells both in vitro and in vivo . Microscopic examination revealed that autoaggregating cells adhered in clusters, with adhesion being mediated by only a few bacteria, whereas the hemagglutinating and nonautoaggregating strains adhered individually or in small groups making contact with each epithelial cell with the entire bacterial surface . The in vitro assessment of adhesion was a good indication of the in vivo association of propionibacteria with the intestinal epithelium . Therefore, the in vitro method presented here should be valuable in screening routinely adhesive properties of propionibacteria for probiotic purposes . The adhesion ability of dairy propionibacteria would prolong their maintenance in the gut and increase the duration of their provision of beneficial effects in the host, supporting the potential of Propionibacterium in the development of new probiotic products.

Eur J Immunol, 2002 Mar, 32(3), 761 - 72
Expression and role of CD14 in mice sensitized to lipopolysaccharide by Propionibacterium acnes; Merlin T et al.; Propionibacterium acnes-primed mice develop an IFN-gamma-dependent hypersensitivity towards LPS . Since CD14 plays a key role in LPS-induced cell activation the regulation and function of CD14 in this sensitization process were studied in IFN-gamma R-/- and the respective wild-type (wt) mice . In unprimed mice, CD14 (mRNA and protein) was either absent (liver) or only weakly expressed in organs (spleen, lung) and in plasma . Priming with P . acnes led to a moderate, mainly IFN-gamma-dependent up-regulation of CD14 . LPS challenge of unprimed mice induced an IFN-gamma-independent increase in CD14 mRNA and CD14 protein . LPS challenge of P . acnes-primed mice induced a strong CD14 overexpression . This response was completely absent in IFN-gamma R-/- mice and is therefore strictly IFN-gamma-dependent . The requirement for CD14 in LPS hyper-responsiveness was assessed by comparing CD14-/- and the respective wt mice with respect to their ability to produce TNF and IFN-gamma, two recognized indices of LPS activity . LPS challenge without priming led to a weaker cytokine reaction in CD14-/- than in wt mice . However, priming with P . acnes enhanced the cytokine response to LPS in both wt and CD14-/- mice, although in the latter absolute levels of cytokines were lower . Therefore, hyperreactivity to LPS is characterized by an up-regulation of CD14, but the sensitization by P . acnes is not CD14 dependent.

J Infect, 2001 Nov, 43(4), 249 - 51
Ventricular patch endocarditis caused by Propionibacterium acnes: advantages of gallium scanning; Vandenbos F et al.; Propionibacterium acnes is a weakly pathogenic commensal of the skin . When isolated from blood cultures it is often considered a contaminant . However, P . acnes may be responsible for severe infections and its role in certain cases of infectious endocarditis has now been definitely established.(1) We report a case of endocarditis due to P . acnes stemming from a ventricular patch and revealed by a gallium 67 scan .

Int Endod J, 2002 Jan, 35(1), 13 - 21
Effects of instrumentation, irrigation and dressing with calcium hydroxide on infection in pulpless teeth with periapical bone lesions; Peters LB et al.; AIM: The aim of this study was to evaluate the fate of microorganisms in root canals of teeth with infected pulps and periapical bone lesions with and without the use of calcium hydroxide medication . METHODOLOGY: Endodontic samples were cultured and microorganisms were counted and identified in 43 teeth before (sample 1) and after (sample 2) treatment during the first visit and before (sample 3) and after (sample 4) treatment during the second visit . In the first visit teeth were instrumented and half of the teeth were filled with a thick slurry of calcium hydroxide in sterile saline . The other teeth were obturated with gutta-percha and AH-2 6 sealer . After 4 weeks the teeth with calcium-hydroxide were accessed again and after microbiological sampling they were obturated with gutta-percha and AH-26 sealer . RESULTS: The mean total colony forming unit (CFU) counts of positive samples dropped significantly as a result of canal preparation during the first visit from 1.0 x 10(6) to 1.8 x 10(3) (between samples 1 and 2) but increased to 9.3 x 10(3) in the period between the two visits (sample 2 and 3) . There was no difference in mean total CFU counts of positive samples between the end of the first (sample 2) and the end of the second visit (sample 4) . The most frequently isolated species were Prevotella intermedia, Capnocytophaga spp. . Actinomyces odontolyticus . Propionibacterium acnes and Peptostreptococcus micros . CONCLUSIONS: Although a calcium hydroxide paste was placed in the prepared canals, the number of positive canals had increased in the period between visits . However, the number of microorganisms had only increased to 0.93% of the original number of CFU (sample 1) . It is concluded that a calcium hydroxide and sterile saline slurry limits but does not totally prevent regrowth of endodontic bacteria.

J Eur Acad Dermatol Venereol, 2001, 15 Suppl 3, 51 - 5
Current issues in antimicrobial therapy for the treatment of acne; Leyden JJ; This review summarizes current information regarding the use of antimicrobial agents for the treatment of patients with inflammatory acne . A number of drugs have been used effectively as topical or systemic therapy, often in combination with benzoyl peroxide or a retinoid . Propionibacterium acnes exhibits high in vitro sensitivity to a wide range of antimicrobials, including ampicillin, clindamycin, erythromycin, tetracycline, doxycycline, nadifloxacin, ofloxacin, minocycline, cephalexin, and gentamycin . However, not all of these drugs are equally effective in penetrating the lipid-filled microcomedo and reducing numbers of P . acnes in the skin . Antimicrobial therapy, particularly systemic treatment, may be complicated by the potential for drug-drug interactions . Historically, the potential for antimicrobials to reduce the effectiveness of oral contraceptives has been a concern in the treatment of acne . However, there is evidence to suggest that such an interaction does not take place in patients being treated with the antimicrobials most often used in dermatological practice . Antimicrobial therapy for acne has also been complicated by the emergence of antibiotic-resistant strains of P . acnes . Increasing P . acnes resistance can be combated by judicious use of retinoids in combination with antibiotics to reduce inflammation and infection, and employment of retinoids for maintenance therapy.

J Eur Acad Dermatol Venereol, 2001, 15 Suppl 3, 43 - 9
The integral role of topical and oral retinoids in the early treatment of acne; Shalita A; This article will review the rationale for early use of topical retinoids alone or in combination with topical antimicrobials in light of the pathogenesis of microcomedones and later lesions . Knowledge of the pathogenic processes in acne vulgaris has risen dramatically over the last three decades . It is now widely accepted that acne is the result of four distinct processes: increased proliferation, cornification, and shedding of follicular epithelium; increased sebum production; colonization of the follicle with Propionibacterium acnes; and induction of inflammatory responses by bacterial antigens and cell signals . Clinical focus of disease management has shifted toward earlier treatment targeting these fundamental processes . Elimination of microcomedones, the precursor to all subsequent lesions, would optimize acne therapy by preventing the later inflammatory stages of disease . With the exception of oral isotretinoin, no single first-line agent addresses all pathogenic mechanisms . Topical retinoids have comedolytic and in some cases anti-inflammatory effects, but have no direct impact on P . acnes . Thus treatment with a combination of topical retinoid and topical antimicrobial is warranted . The former can also enhance penetration of the latter by increasing microcomedonal extrusion . In selecting a combination, one must consider efficacy, cost, and likelihood of compliance . Once thought to be effective primarily for treating comedones, topical retinoids have also been demonstrated to be effective in reducing inflammatory lesions . The activity of a topical retinoid combined with an antimicrobial agent has been shown to clear more lesions and to clear them more rapidly than antimicrobial therapy alone . Topical retinoids are also used effectively to maintain remissions.

Cell Death Differ, 2002 Feb, 9(2), 179 - 88
Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain fatty acids acting on mitochondria; Jan G et al.; The genus Propionibacterium is composed of dairy and cutaneous bacteria which produce short-chain fatty acids (SCFA), mainly propionate and acetate, by fermentation . Here, we show that P . acidipropionici and freudenreichii, two species which can survive in the human intestine, can kill two human colorectal carcinoma cell lines by apoptosis . Propionate and acetate were identified as the major cytotoxic components secreted by the bacteria . Bacterial culture supernatants as well as pure SCFA induced typical signs of apoptosis including a loss of mitochondrial transmembrane potential, the generation of reactive oxygen species, caspase-3 processing, and nuclear chromatin condensation . The oncoprotein Bcl-2, which is known to prevent apoptosis via mitochondrial effects, and the cytomegalovirus-encoded protein vMIA, which inhibits apoptosis and interacts with the mitochondrial adenine nucleotide translocator (ANT), both inhibited cell death induced by propionibacterial SCFA, suggesting that mitochondria and ANT are involved in the cell death pathway . Accordingly, propionate and acetate induced mitochondrial swelling when added to purified mitochondria in vitro . Moreover, they specifically permeabi-lize proteoliposomes containing ANT, indicating that ANT can be a critical target in SCFA-induced apoptosis . We suggest that propionibacteria could constitute probiotics efficient in digestive cancer prophylaxis via their ability to produce apoptosis-inducing SCFA.

J Dermatol, 2002 Jan, 29(1), 20 - 2
Minocycline effectively reduces acid producted by Propionibacterium granulosum; Higaki S et al.; We studied the effects of minocycline on Propionibacterium granulosum . P . granulosum lipase activity was detected from acne lesions . Production of propionic and butyric acids by P . granulosum was well suppressed by all tested media with added minocycline; the higher the concentration of minocycline in the medium, the less of these acids was produced . It appeared that the decrease in these acids due to minocycline was greater in P . granulosum than in P . acnes . Although the influence of P . granulosum on acne lesions might be feebler than that of P . acnes, we should not neglect its presence . More research is needed to elucidate the relationship between the two species in acne lesions.

Clin Infect Dis, 2002 Mar 15, 34(6), 853 - 4 Epub 2002 Jan 31.
Propionibacterium acnes chest infections in patients with chronic granulomatous disease: case reports; Bourdeaut F et al.; Antibiotic prophylaxis in patients with chronic granulomatous disease (CGD) has decreased the prevalence of infections, but uncommon microorganisms are being observed more frequently . Propionibacterium acnes, a saprophyte of the skin, is generally not involved in infections other than acne . Two cases of P . acnes extracutaneous infections in teenagers with CGD are reported.

Appl Environ Microbiol, 2002 Feb, 68(2), 608 - 15
Conversion of L-leucine to isovaleric acid by Propionibacterium freudenreichii TL 34 and ITGP23; Thierry A et al.; Several branched-chain volatile compounds are involved in the flavor of Swiss cheese . These compounds are probably produced by enzymatic conversion of branched-chain amino acids, but the flora and the pathways involved remain hypothetical . Our aim was to determine the ability of Propionibacterium freudenreichii, which is one of the main components of the secondary flora of Swiss cheese, to produce flavor compounds during leucine catabolism . Cell extracts and resting cells of two strains were incubated in the presence of L-leucine, alpha-ketoglutaric acid, and cofactors, and the metabolites produced were determined by high-performance liquid chromatography and gas chromatography . The first step of leucine catabolism was a transamination that produced alpha-ketoisocaproic acid, which was enzymatically converted to isovaleric acid . Both reactions were faster at pH 8.0 than at acidic pHs . Cell extracts catalyzed only the transamination step under our experimental conditions . Small amounts of 3-methylbutanol were also produced by resting cells, but neither 3-methylbutanal noralpha-hydroxyisocaproic acid was detected . L-Isoleucine and L-valine were also converted to the corresponding acids and alcohols . Isovaleric acid was produced by both strains during growth in a complex medium, even under conditions simulating Swiss cheese conditions (2.1% NaCl, pH 5.4, 24 degrees C) . Our results show that P . frendenreichii could play a significant role in the formation of isovaleric acid during ripening.

Eur J Ophthalmol, 2001 Oct-Dec, 11(4), 383 - 5
Propionibacterium acnes endophthalmitis in Ahmed glaucoma valve; Gutierrez-Diaz E et al.; PURPOSE: To report a case of Propionibacterium acnes endophthalmitis in a patient with an Ahmed glaucoma valve . CASE REPORT: A nine-year-old boy with bilateral congenital glaucoma, with an Ahmed glaucoma valve implanted in the left eye, had recurrent conjunctival dehiscence and endophthalmitis . RESULTS: Vitreous cultures demonstrated the presence of Propionibacterium acnes . CONCLUSIONS: This is the first reported case of Propionibacterium acnes endophthalmitis in an Ahmed glaucoma valve and the second one in a glaucoma drainage device . We strongly recommend using a patch graft to prevent and treat tube exposure . Conjunctival grafts may be useful to close the conjunctiva when there is marked scarring to prevent patch exposure and melting or extrusion.

World J Gastroenterol, 1998 Feb, 4(1), 14 - 18
CCR5 gene expression in fulminant hepatitis and DTH in mice; Guo BY et al.; AIM:To isolate mouse CCR5 cDNA (muCCR5) and study its expression in vivo.METHODS: Marathon PCR was used to isolate muCCR5 cDNA and two animal models were designed to investigate the gene expression in vivo, one was mouse fulminant hepatitis induced by Propionibacterium acnes (P.acnes) and the other was that with delayed type hypersensitivity reaction (DTH) . A specific GST-NH2-terminus of muCCR5 fusion protein antibody F(ab')(2) was prepared and clarified . RT-PCR and immunohistochemical analysis were used to observe the expression level of CCR5 gene in mice.RESULTS: A positive reaction of mouse macrophage was found in DTH but not expressed in P.acnes induced fulminant hepatitis by RT-PCR and immunohistochemical analysis.CONCLUSION: This muCCR5 expression may be involved in an allergic processmediated by cellular immunity but not acute inflammatory reaction induced by P.acnes.

Eur J Dermatol, 2002 Jan-Feb, 12(1), 53 - 7
The effect of benzoyl peroxide and benzoyl peroxide/erythromycin combination on the antioxidative defence system in papulopustular acne; Basak PY et al.; Acne vulgaris is a common, inflammatory disease of the pilosebaceous duct . Propionibacterium acnes proliferated in sebum, produces chemotactic factors followed by phagocytosis and this process results in the production of reactive oxygen species which contribute to the inflammatory reaction in papulopustular type acne . Benzoyl peroxide (BP) and BP combination with erythromycin (BP/E) are effective topical medications for the treatment of mild and moderate acne vulgaris . In the present study, the effects of BP and BP/E on antioxidant defence enzymes in 40 patients with papulopustular type acne were evaluated . The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and also thiobarbituric acid reactive substance (TBARS) levels were determined in peripheral blood leukocytes in all patients, as well as in tissues of a small group of patients before and at the end of 4 weeks of treatment . No difference was detected in leukocyte antioxidant enzyme activities and TBARS levels due to BP treatment . However, SOD, CAT and GSH-Px activities in leukocytes decreased and TBARS levels increased in BP/E-treated patients (p < 0.05) . There was no statistically significant difference between pretreatment and posttreatment enzyme activities in tissue samples . The results of this preliminary study may be attributable to in vivo conditions and possible stability problems while compounding the mixture of the BP/E . Influence of the other ingredients of the formulations applied in the study must also be considered.

J Immunol, 2002 Jan 15, 168(2), 537 - 40
Cutting edge: Th2 response induction by dendritic cells: a role for CD40; MacDonald AS et al.; We investigated the influence of dendritic cell (DC) CD40 expression on Th2 and Th1 development by in vivo transfer of Ag-pulsed bone marrow-derived DC generated from wild-type (WT) or CD40(-/-) mice . Contrary to expectation, CD40(-/-) DC primed with Ag that inherently induce a Th2 response (soluble egg Ag from Schistosoma mansoni) failed to induce a Th2 response or any compensatory Th1 response, whereas CD40(-/-)DC primed with Ag that inherently induce a Th1 response (Propionibacterium acnes) generated a competent Th1 response . Thus, DC expression of CD40 is a prerequisite for initiation of Th2, but not Th1, responses by these Ag . Consistent with this, CD154(-/-) mice, unlike WT mice, failed to mount a Th2 response when directly injected with schistosome eggs but mounted a normal Th1 response after challenge with P . acnes . CD40-CD154 interaction can therefore play a major role in Th2 response induction.

Head Neck, 2002 Jan, 24(1), 84 - 6
Anaerobic thyroid abscess from a thyroid cyst after fine-needle aspiration; Sun JH et al.; BACKGROUND: Anaerobic abscess formation within a thyroid cyst is rare but still possible, although aerobic thyroid abscess formation in the thyroid gland after fine-needle aspiration (FNA) has been observed in immunocompromised patients . METHODS: This study describes the clinical manifestations, thyroid echography, cytologic finding, culture outcome, and treatment course of an anaerobic abscess formation within a thyroid cyst after FNA in a healthy subject . RESULTS: A 53-year-old male subject had rapid enlargement of a left thyroid cyst develop after second FNA . Frank pus was obtained through third FNA . The culture outcome was Propionibacterium acnes, which was rich in saliva and one of the pathogens causing periodontitis and gingivitis . After adequate antimicrobial therapy, the abscess gradually diminished . CONCLUSIONS: This article reported, for the first time, on the formation of an anaerobic thyroid abscess after FNA in a healthy subject . We recommended careful aseptic procedure and adequate isolation processes, such as wearing a mask to avoid an unfavorable outcome as a result of a bacterial infection .

J Clin Microbiol, 2002 Jan, 40(1), 198 - 204
Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis; Eishi Y et al.; The cause(s) of sarcoidosis is unknown . Mycobacterium spp . are suspected in Europe and Propionibacterium spp . are suspected in Japan . The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species . Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England . Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp . paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR . Either P . acnes or P . granulosum was found in all but two of the sarcoid samples . M . avium subsp . paratuberculosis was found in no sarcoid sample . M . tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples . In sarcoid lymph nodes, the total numbers of genomes of P . acnes or P . granulosum were far more than those of M . tuberculosis . P . acnes or P . granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P . acnes or P . granulosum in such samples were less than those in sarcoid samples . Propionibacterium spp . are more likely than Mycobacteria spp . to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.

Med Dosw Mikrobiol, 2001, 53(2), 167 - 75
{Use of the Etest method for antimicrobial susceptibility testing of obligate anaerobes}; Rokosz A et al.; The aim of this study was to evaluate Etest usefulness for antimicrobial susceptibility testing of obligate anaerobes and to compare the activity of five antibacterial drugs against clinical strains of anaerobes . One hundred strains of obligate anaerobes were tested: 2 reference strains (B . fragilis ATCC 25285 and B . thetaiotaomicron ATCC 29741) and 98 clinical strains isolated from patients of the Infant Jesus Clinical Hospital--Center for Trauma Treatment in Warsaw during the last three years (1997-1999) . Strains of seven genera of obligate nonsporeforming anaerobes (Bacteroides, Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Propionibacterium and Actinomyces) and strains of two sporeforming species (C . perfringens and C . difficile) were examined . The MIC values were determined by the gradient diffusion method Etest (AB BIODISK, Sweden) . Wilkins-Chalgren solid medium supplemented with 5% of sheep blood was used . Test plates were incubated at 35 degrees C for 48 hours in glove-box (85% N2, 10% H2, 5% CO2) . The MIC values for each strain and antimicrobial agent, and the MIC ranges for bacteria of the same species were established . Ten strains resistant to clindamycin, ten resistant to piperacillin, and ten resistant to imipenem were detected . Seven strains were resistant to metronidazole and two strains to piperacillin combined with tazobactam . Tazobactam restored the susceptibility of eight strains to piperacillin . Obtained results confirm that Etest method is useful for antimicrobial susceptibility testing of obligate anaerobes . Older (clindamycin and metronidazole) and newer (piperacillin, piperacillin/tazobactam and imipenem) antimicrobial agents revealed high and comparable activity against clinical strains of obligate anaerobes . The percentage of strains susceptible to tested antimicrobials was > or = 90 . These antimicrobials may be still useful in the empiric treatment of infections caused by medically important anaerobes.

Infect Immun, 2001 Dec, 69(12), 7271 - 6
Differences in innate defense mechanisms in endotoxemia and polymicrobial septic peritonitis; Echtenacher B et al.; Loss, reduction, or enhancement of the ability to respond to bacterial lipopolysaccharide (LPS) has no influence on survival of mice in a model of postoperative polymicrobial septic peritonitis induced by cecal ligation and puncture (CLP) . This was demonstrated by using either mice with a defective Tlr4 gene, which encodes the critical receptor molecule for LPS responses, or mice deficient for LPS binding protein (LBP) or mice sensitized to LPS by Propionibacterium acnes . Though interleukin-12 (IL-12) and gamma interferon (IFN-gamma) play an important role in the sensitivity to LPS as well as in the resistance to several infections, loss of these cytokine pathways does not affect survival after CLP . Thus, neutralization of neither endogenous IL-12 nor IFN-gamma altered mortality . In addition, IFN-gamma receptor-deficient mice demonstrated the same sensitivity to CLP as mice with a functional IFN-gamma receptor . However, administration of IFN-gamma at the time of operation or pretreatment of both IFN-gamma-sensitive and IFN-gamma-resistant mice with IL-12 significantly enhanced mortality . This indicates that in the present infection model activation of innate defense mechanisms is not dependent on LPS recognition and does not require endogenous IL-12 or IFN-gamma function . Indeed, exogenous application of these two mediators had deleterious effects.

Am J Clin Dermatol, 2001, 2(4), 263 - 6
The combination formulation of clindamycin 1% plus benzoyl peroxide 5% versus 3 different formulations of topical clindamycin alone in the reduction of Propionibacterium acnes . An in vivo comparative study; Leyden J et al.; BACKGROUND: Isolates of Propionibacterium acnes resistant to one or more anti-acne antibiotics (most commonly erythromycin) are being increasingly reported, and the emergence of resistant strains can be associated with therapeutic failure of topical treatment . OBJECTIVE: Comparison of the in vivo effectiveness of the combination of clindamycin 1% plus benzoyl peroxide 5% in a gel formulation to that of each of 3 clindamycin 1% preparations (gel, lotion, and solution) with respect to reduction in counts of P . acnes cultured from the foreheads of healthy volunteers . METHODS: The effects of treatment with the 4 study drugs were compared in an open-label study . Cultures were collected before, after 1 week and after 2 weeks of treatment . RESULTS: Treatment with the combination formulation resulted in a 99.8% (> 2 logs) reduction in total propionibacterial numbers after 1 week of therapy compared with 30 to 62% (< 1 log) decreases for the different formulations of topical clindamycin alone . By the end of week 2, the combination had decreased P . acnes counts by more than 99.9% (> 3 logs) relative to reductions of from 88 to 95% (< or > 1 log) for the single agent formulations . CONCLUSIONS: Under the conditions of the present study, the combination of clindamycin 1% plus benzoyl peroxide 5% gel produced more rapid and highly significant reductions in P . acnes compared with formulations containing clindamycin alone.

Am J Clin Dermatol, 2001, 2(3), 135 - 41
Optimal management of acne to prevent scarring and psychological sequelae; Layton AM; Acne vulgaris is one of the most common inflammatory dermatoses and is seen in both the hospital setting and in general practice . Multiple factors are involved in the pathophysiology of acne, including: an alteration in the pattern of keratinization within the pilosebaceous follicles resulting in comedone formation; an increase in sebum production which is influenced by androgens; the proliferation of Propionibacterium acnes; and the production of perifollicular inflammation . Genetic and hormonal factors may also contribute to acne . Better understanding of the pathophysiology of the disease has led to the development of novel therapies which are directed at one or more of the implicated etiologic factors . Systemic antibiotics for acne have been the mainstay of treatment for many years . The main cause for concern following the use of systemic antibiotics is the emergence of antibiotic-resistant strains of P . acnes . Concomitant use of non-antibiotic therapies such as benzoyl peroxide helps to decrease the occurrence of resistance and can be effective in the treatment of resistant and nonresistant propionibacterial strains . However, no one agent is able to eradicate resistant strains completely and as resistant strains correlate to poor clinical response to therapy, prescribing strategies are required to minimize the occurrence of resistance to P . acnes . When assessing acne it is important to take an all embracing approach and to examine carefully for both the clinical and psychologic effects of the disease process . There are numerous forms of acne scarring and it is important to be aware of these as patients who are developing scarring merit early effective therapy . Some patients with acne will develop psychologic problems as a consequence of their condition . Even mild to moderate disease can be associated with significant depression and suicidal ideation and psychologic change does not necessarily correlate with disease severity . Acne scars themselves have been shown to produce significant psychopathology . When initiating treatment it is important to consider the aims of therapy . Treatment should be aimed at achieving clearance of acne, prevention of scarring and, where necessary, relief from any psychologic stress resulting from the acne . Therapy should be commenced early in the disease process in order to prevent scarring and it is important to select appropriate therapies according to the clinical signs and psychologic disability . It is also important to ensure that the patient is able to comply with therapy and clear guidelines regarding treatment, possible adverse effects and realistic expectations should be provided.

Am J Clin Dermatol, 2000 Jul-Aug, 1(4), 201 - 9
Is acne an infection of blocked pilosebaceous follicles? Implications for antimicrobial treatment; Eady EA et al.; A model is proposed which is based on the assumption that acne is due to infection of functionally blocked pilosebaceous follicles by propionibacteria . Noninflamed lesions, which are first visible during the adrenarche in acne-prone individuals, do not contain propionibacteria . Comedogenesis appears to be independent of bacterial infection and may be driven by high levels of bioactive interleukin-1 alpha derived from ductal hyperkeratinocytes . The stimulus which triggers interleukin-1 alpha production is unknown . Formalin killed Propionibacterium acnes failed to stimulate production of the cytokine by cultured human keratinocytes in vitro . Inflamed lesions are thought to arise from microcomedones, but the initiating events are unknown . Evidence that propionibacteria are involved in the generation of inflammatory lesions is inconclusive . The cellular infiltrate is consistent with a type IV hypersensitivity response to one or more persistent lesional antigens, not necessarily bacterial . The potent adjuvant activity of P . acnes would up-regulate the immune response to any antigen which came into contact with the mononuclear cell infiltrate . Antibiotics are widely used in the treatment of acne, and their effects in selecting a predominantly resistant commensal population are well recognized . Although they reduce numbers of propionibacteria on the skin, other modes of action may contribute to or explain their therapeutic efficacy . At a time when there is global concern that antibiotic resistance rates in common bacterial pathogens may threaten our future ability to control bacterial infections, practices which promote the spread of antibiotic-resistant bacteria must be fully justified . A thorough reappraisal of the role of propionibacteria in acne is overdue . It is likely that further experimental work is needed to confirm or refute that P . acnes is aptly named.

Biophys J, 2001 Nov, 81(5), 2838 - 50
Motility of single one-headed kinesin molecules along microtubules; Inoue Y et al.; The motility of single one-headed kinesin molecules (K351 and K340), which were truncated fragments of Drosophila two-headed kinesin, has been tested using total internal reflection fluorescence microscopy . One-headed kinesin fragments moved continuously along the microtubules . The maximum distance traveled until the fragments dissociated from the microtubules for both K351 and K340 was approximately 600 nm . This value is considerably larger than the space resolution of the measurement system (SD approximately 30 nm) . Although the movements of the fragments fluctuated in forward and backward directions, statistical analysis showed that the average movements for both K340 and K351 were toward the plus end of the microtubules, i.e., forward direction . When BDTC (a 1.3-S subunit of Propionibacterium shermanii transcarboxylase, which binds weakly to a microtubule), was fused to the tail (C-terminus) of K351, its movement was enhanced, smooth, and unidirectional, similar to that of the two-headed kinesin fragment, K411 . However, the travel distance and velocity of K351BDTC molecules were approximately 3-fold smaller than that of K411 . These observations suggest that a single kinesin head has basal motility, but coordination between the two heads is necessary for stabilizing the basal motility for the normal level of kinesin processivity.

Appl Microbiol Biotechnol, 2001 Sep, 56(5-6), 676 - 80
Propionic acid production in an in situ cell retention bioreactor; Goswami V et al.; Continuous fermentations were conducted with in situ cell retention using spin filters (pore size 5 microm and 10 microm) for propionic acid production by Propionibacterium acidipropionici . Continuous fermentation with a 5-microm pore size spin filter resulted in 50% cell retention . Propionic acid productivity was enhanced (0.9 g l(-1) h(-1)) by approximately four-fold compared to conventional batch fermentation (0.25 g l(-1) h(-1)) . The in situ cell retention (5-microm pore size spin filter) bioreactor was operated continuously and smoothly for 8 days at a dilution rate of D=0.05 h(-1).

Semin Cutan Med Surg, 2001 Sep, 20(3), 139 - 43
The evolving role of Propionibacterium acnes in acne; Leyden JJ; Propionibacterium acnes is a member of the resident cutaneous flora . Sebaceous follicles involved in acne are characterized by the accumulation of abnormally desquamated corneocytes and excess sebum-the microcomedo . This environment provides ideal growth conditions for P acnes . Several orders of magnitude level of P acnes are found in microcomedos . P acnes produces a variety of chemotactic factors and proinflammatory molecules that are responsible for the inflammatory phase of acne . Antibiotic therapy works by reducing the viable number of P acnes as well as by reducing the production of inflammatory stimuli . Antibiotic therapy has been a mainstay of treatment for more than 30 years . In the last decade, decreased sensitivity to antibiotics has developed and clinical resistance has been described . This development threatens the usefulness of antibiotic therapy in the future.

Can J Microbiol, 2001 Aug, 47(8), 735 - 40
Reduction of linoleic acid inhibition in production of conjugated linoleic acid by Propionibacterium freudenreichii ssp . shermanii; Rainio A et al.; A method for the production of conjugated linoleic acid (CLA) from linoleic acid (LA) using growing cultures of Propionibacterium freudenreichii ssp . shermanii JS was developed . The growth inhibitory effect of LA was eliminated by dispersing it in a sufficient concentration of polyoxyethylene sorbitan monooleate detergent . For the whey permeate medium used, the optimum LA:detergent ratio was 1:15 (w/w) . As a result, the cultures tolerated at least 1000 microg x mL(-1) LA, which was converted to CLA with 57%-87% efficiency . The cis-9, trans-11 and trans-9, cis-11 isomers constituted 85%-90% of the CLA produced . The feasibility of the method was demonstrated also in de Man Rogosa-Sharpe (MRS) broth.

Int J Food Microbiol, 2001 Aug 15, 68(1-2), 45 - 52
Characterization of the 16S-23S and 23S-5S rRNA intergenic spacer regions of dairy propionibacteria and their identification with species-specific primers by PCR; Tilsala-Timisjarvi A et al.; In this study, the 16S-23S and 23S-5S rRNA intergenic spacer region sequences of Propionibacterium acidipropionici, P . freudenreichii ssp . freudenreichii and ssp . shermanii, P . jensenii and P . thoenii were determined . The sequences were shown to vary greatly between the species . Specific primer pairs were derived from the 16S-23S rRNA spacer sequences and used for the identification of the species by PCR.

Br J Dermatol, 2001 Sep, 145(3), 463 - 6
A clinical and therapeutic study of 29 patients with infantile acne; Cunliffe WJ et al.; BACKGROUND: Infantile acne is a relatively uncommon condition; there are few data in the literature on the optimum treatment for this disorder . OBJECTIVES: To review treatment results in infantile acne . METHODS: We performed a retrospective review of 29 patients (24 boys and five girls) treated over a 25-year period . RESULTS: The age at onset was 6-16 months (median 9) . The acne was mild in 24%, moderate in 62% and severe in 14% . The type of acne was predominantly inflammatory (59%), but was comedonal in 17%, showed a mixed pattern in 17% and was nodular in 7% . No infants had any clinically obvious endocrinopathy . Patients with mild acne responded well to topical treatment (benzoyl peroxide, erythromycin and retinoids) . All but two infants with moderate acne responded well to oral (paediatric) erythromycin 125 mg twice daily and topical therapy . Patients with erythromycin-resistant Propionibacterium acnes required trimethoprim 100 mg twice daily . Most patients were able to stop oral antibiotics within 18 months . In 38% of children, long-term oral antibiotics (> 24 months) were required . The time for clearance of the acne was 6-40 months (median 18) . One patient required oral isotretinoin that cleared the acne in 4 months . Five patients (17%) were left with scarring . CONCLUSIONS: This study confirms the male predominance of infantile acne . Treatment is similar to that of adult acne, with the exclusion of the use of tetracyclines . When necessary, oral isotretinoin can be used.

Eur J Hum Genet, 2001 Aug, 9(8), 577 - 82
N219Y, a new frequent mutation among mut(degree) forms of methylmalonic acidemia in Caucasian patients; Acquaviva C et al.; Mutations in the MUT locus encoding for the methylmalonyl-CoA mutase (MCM) apoenzyme are responsible for the mut forms of methylmalonic acidemia (MMA) . To date, 49 different mutations have been identified in mut MMA . Only two frequent mutations have been reported in the Japanese population and in African-Americans . Here we report a new missense mutation N219Y (731 A-->T) which we found in five unrelated families of French and Turkish descent . All the patients exhibited a severe mut(degree) phenotype and three of them were homozygotes for N219Y . Direct involvement of the mutation in the loss of enzyme activity was demonstrated by mutagenesis and transient expression study . Mapping of the mutation onto a three-dimensional model of human MCM constructed by homology with the Propionibacterium shermanii enzyme shows that it lies in a highly conserved secondary structure motif and might suggest impaired folding and/or poor stability compatible with the mut(degree) phenotype . Finally, a 1% N219Y carrier frequency was observed in a French anonymous control population . Thus, N219Y is the first frequent mut mutation to be reported in the Caucasian population.

Neurosurgery, 2001 Sep, 49(3), 717 - 20
Focal intracranial infections due to Propionibacterium acnes: report of three cases; Chu RM et al.; OBJECTIVE AND IMPORTANCE: Except for its role in shunt infections, Propionibacterium acnes has been of little interest to neurosurgeons . The rarity and indolent nature of focal intracranial infections by P . acnes limit their recognition . Three cases of serious intracranial infection due to this organism are described . CLINCAL PRESENTATION: Three patients with histories of immunosuppression and neurosurgical procedures developed nonspecific, delayed presentations (5 wk to 5 yr after surgery) of intracranial infections . In two patients, radiological investigations showed enhancing lesions that were later found to be brain abscesses . A subdural empyema was found in the third patient . INTERVENTION: All three patients underwent surgical drainage of the purulent collections . P . acnes was isolated in each case, and each patient was treated with a 6-week course of intravenous penicillin . All three patients made good recoveries, and subsequent imaging showed no recurrence of the infectious collections . CONCLUSION: P . acnes is an indolent organism that may rarely cause severe intracranial infections . This organism should be suspected when an intracranial purulent collection is discovered in a patient with a history of neurosurgical procedures . Immunosuppressed patients may be susceptible to this otherwise benign organism . Surgical drainage and treatment with intravenous penicillin should be considered standard therapy.

Appl Microbiol Biotechnol, 2001 Jul, 56(1-2), 144 - 9
Construction of an expression vector for propionibacteria and its use in production of 5-aminolevulinic acid by Propionibacterium freudenreichii; Kiatpapan P et al.; Several promoters from Propionibacterium freudenreichii subsp . shermanii were isolated using a promoter probe vector, pCVE1, containing the Streptomyces cholesterol oxidase gene (choA) as a reporter gene . Three of four promoters isolated exhibiting a strong activity in Escherichia coli also expressed a strong activity in P . freudenreichii subsp . shermanii IFO12426 . Using two promoters with a strong activity and a previously constructed shuttle vector, pPK705, shuttling between E . coli and Propionibacterium . we constructed expression vectors for propionibacteria . To overproduce 5-aminolevulinic acid (ALA), which is the first intermediate in the synthesis of porphyrins, the ALA synthase gene (hemA) from Rhodobacter sphaeroides was recombined with the expression vectors . The activity of ALA synthase in the recombinant P freudenreichii subsp . shermanii increased about 70-fold that in the strain without a vector . The recombinant Propionibacterium produced ALA at a maximum concentration of 8.6 mM in the absence of levulinic acid, an inhibitor of ALA dehydratase, with 1% glucose as a carbon source . The recombinant P . freudenreichii accumulated 18.8 mmol/g cells ALA in the presence of 1 mM levulinic acid and 30 mM glycine . The construction of an efficient expression vector will facilitate genetic studies of a vitamin B12 producer, Propionibacterium.

Int J Syst Evol Microbiol, 2001 Jul, 51(Pt 4), 1373 - 82
Propionibacterium microaerophilum sp . nov., a microaerophilic bacterium isolated from olive mill wastewater; Koussemon M et al.; A new gram-positive, facultative anaerobic, microaerophilic bacterium, designated strain M5T, was isolated from a decantation reservoir of olive mill wastewater . The cells were rod-shaped, non-motile, non-spore-forming and catalase-negative . Growth occurred at pH ranging from 4.5 to 9.5, with optimum growth at 7.0 . The optimum temperature for growth was around 30 degrees C . Although growth occurred under anaerobic and aerobic conditions, the optimum O2 concentration for growth was determined as 5% in the gas phase of the culture . During anaerobic growth, glucose or lactate were mainly fermented to propionate, acetate and CO2 . In the presence of O2 (more than 2%), glucose was oxidized completely to CO2 . The G+C content of the DNA was 67.7+/-0.6 mol% and 16S rRNA gene analysis revealed that the new isolate belonged to the cluster of 'dairy' propionibacteria, Propionibacterium acidipropionici being its closest phylogenic relative (97.5% similarity) . However, the level of DNA relatedness between strain M5T and P . acidipropionici was 56.2% . Consequently, both the phenotypic (range of substrates used) and genotypic characteristics of strain M5T allow it to be assigned as a new species of the genus Propionibacterium, Propionibacterium microaerophilum sp . nov . The type strain is strain M5T (= CNCM I-2360T = DSM 13435T).

Biotechnol Prog, 2001 Jul-Aug, 17(4), 669 - 75
Study and mathematical modeling of the production of propionic acid by Propionibacterium acidipropionici immobilized in a stirred tank fermentor; Coronado C et al.; A mathematical model was developed that describes production of propionic acid by fermentation of sweet whey with Propionibacterium acidipropionici immobilized in calcium polygalacturonate beads in a fermentor-type stirred tank . This mathematical model is constituted by a partial differential equations system, which fits consumption, production, growth and internal diffusion rates in the support . Fermentation was experimentally studied with free cells and immobilized cells, effective diffusivities of lactose and propionic acid were estimated in the support, and typical parameters of the model were obtained by nonlinear regression of the experimental data . The variance analysis shows that the combination of micro(max) and K(d) parameters is the source of variation most significative, also they were found to be the most sensitive parameters of the model . Finally, an effectiveness factor was calculated in order to assess the effect of mass transfer on the overall reaction rate observed.

Med Electron Microsc, 2001 Mar, 34(1), 29 - 40
Pathogenesis of acne; Toyoda M et al.; Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood . The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation . The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back . At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification . The increased activity of sebaceous glands elicited by androgen causes proliferation of P . acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts . The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture . In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P . acnes . To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy . Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands . It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands . In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view . An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.

Am J Ophthalmol, 2001 Aug, 132(2), 259 - 61
Optic disk edema as a presentation of Propionibacterium acnes endophthalmitis; Kouyoumdjian GA et al.; PURPOSE: To report a patient with an initial presentation of optic disk edema secondary to Propionibacterium acnes endophthalmitis . METHODS: Interventional case report . The patient had surgery and treatment related to endophthalmitis . Nine months after cataract surgery with posterior chamber lens implant, a 79-year-old man receiving topical corticosteroids in the same eye presented with best-corrected visual acuity of 20/60, a superior visual field defect, and optic nerve edema without intraocular inflammation . One year postoperatively, the eye presented a further decrease in best-corrected visual acuity, and a dense white plaque was noted on the posterior capsule . RESULTS: One year postoperatively, a partial capsulectomy with vitrectomy and injection of intravitreal antibiotics was performed . Hematoxylin and eosin stain of the posterior capsule plaque revealed gram-positive coccobacilli characteristic of P . acnes . CONCLUSION: Propionibacterium acnes endophthalmitis may present after cataract surgery with intraocular lens implant with decreased vision, optic disk edema, and a visual field defect.

Structure (Camb), 2001 Jul 3, 9(7), 637 - 46
Crystal structure of methylmalonyl-coenzyme A epimerase from P . shermanii: a novel enzymatic function on an ancient metal binding scaffold; McCarthy AA et al.; BACKGROUND: Methylmalonyl-CoA epimerase (MMCE) is an essential enzyme in the breakdown of odd-numbered fatty acids and of the amino acids valine, isoleucine, and methionine . Present in many bacteria and in animals, it catalyzes the conversion of (2R)-methylmalonyl-CoA to (2S)-methylmalonyl-CoA, the substrate for the B12-dependent enzyme, methylmalonyl-CoA mutase . Defects in this pathway can result in severe acidosis and cause damage to the central nervous system in humans . RESULTS: The crystal structure of MMCE from Propionibacterium shermanii has been determined at 2.0 A resolution . The MMCE monomer is folded into two tandem betaalphabetabetabeta modules that pack edge-to-edge to generate an 8-stranded beta sheet . Two monomers then pack back-to-back to create a tightly associated dimer . In each monomer, the beta sheet curves around to create a deep cleft, in the floor of which His12, Gln65, His91, and Glu141 provide a binding site for a divalent metal ion, as shown by the binding of Co2+ . Modeling 2-methylmalonate into the active site identifies two glutamate residues as the likely essential bases for the epimerization reaction . CONCLUSIONS: The betaalphabetabetabeta modules of MMCE correspond with those found in several other proteins, including bleomycin resistance protein, glyoxalase I, and a family of extradiol dioxygenases . Differences in connectivity are consistent with the evolution of these very different proteins from a common precursor by mechanisms of gene duplication and domain swapping . The metal binding residues also align precisely, and striking structural similarities between MMCE and glyoxalase I suggest common mechanisms in their respective epimerization and isomerization reactions.

J Chemother, 2001 Jun, 13(3), 299 - 308
Effect of perorally administered pivmecillinam on the normal oropharyngeal, intestinal and skin microflora; Sullivan A et al.; To study the ecological effects of pivmecillinam on the human oropharyngeal, intestinal and skin microflora, 15 healthy volunteers were given pivmecillinam tablets 400 mg twice daily for 7 days . Saliva, stool and skin specimens were taken before (days -3 and 0) and on the 2nd, 4th and 7th days during the administration period and 14 and 21 days after the start of administration . Mecillinam caused no major changes in the aerobic or anaerobic oropharyngeal microflora . In the aerobic intestinal microflora there was a decrease in the numbers of Escherichia coli while no changes occurred in the anaerobic microflora . In the skin microflora there was a transient decrease in the numbers of Propionibacterium spp . underneath the wing of the nose . The major effect of pivmecillinam was seen on E . coli and to some extent on Propionibacterium spp . No further ecological disturbances were noticed in the oropharyngeal, intestinal or skin microflora.

Scand J Infect Dis, 2001, 33(5), 379 - 80
Propionibacterium acnes endocarditis in a native valve complicated by intraventricular abscess: a case report and review; Mohsen AH et al.; Propionibacterium acnes is a constituent of the normal skin flora . It has been described as causing infection on prosthetic valves but very rarely on native valves . We describe a case of aggressive P . acnes endocarditis in a healthy 36-y-old man which infected a native aortic valve and was complicated by an aortic root abscess and review the literature.

J Am Acad Dermatol, 2001 Jul, 45(1), 109 - 17
Acne scarring: a classification system and review of treatment options; Jacob CI et al.; Acne is a common condition experienced by up to 80% of people between 11 and 30 years of age and by up to 5% of older adults . In some patients, the severe inflammatory response to Propionibacterium acnes results in permanent, disfiguring scars . Over the past several decades, numerous descriptive terms and surgical techniques have been used to diagnose the types, and improve the appearance, of scarring in those persons with acne . We propose a descriptive, simple, universally applicable acne scar classification system that includes 3 scar types: icepick, rolling, and boxcar . We also have developed an effective treatment algorithm for reconstructing and improving the appearance of acne scars including punch excision, punch elevation, subcutaneous incision (Subcision), and laser skin resurfacing . This new classification system for acne scars enables the physician to more precisely identify scar subtypes . Once the scar type has been defined, appropriate and effective treatment protocols can be developed.

Curr Opin Ophthalmol, 2001 Jun, 12(3), 225 - 9
Treatment of Propionibacterium acnes endophthalmitis; Deramo VA et al.; Propionibacterium acnes is a well-known cause of delayed endophthalmitis following cataract surgery . A white intracapsular plaque, keratic precipitates, and hypopyon may be present . Although there is no consensus on the treatment approach, recent studies have reviewed the outcomes of relatively large numbers of patients . Reasonable treatment options include pars plana vitrectomy and intra-ocular antibiotics with either partial or total capsulectomy/lens exchange . A good visual outcome is possible.

J Appl Microbiol, 2001 May, 90(5), 788 - 96
Study of the effects of temperature, pH and yeast extract on growth and exopolysaccharides production by Propionibacterium acidi-propionici on milk microfiltrate using a response surface methodology; Gorret N et al.; AIMS: To study the effects of temperature, pH and yeast extract (YE) concentration on growth and exopolysaccharide (EPS) production by Propionibacterium acidi-propionici DSM 4900 cultivated on milk microfiltrate . METHODS AND RESULTS: A multifactorial approach using a Response Surface Methodology (RSM) was followed . The results indicated that both growth, and EPS and organic acids production, were influenced by pH, temperature and YE concentration . Biomass and organic acids production occurred in all the tested domains, whereas EPS production was only possible in a narrow pH range (5.3-6.5) . The results clearly showed that the optimal conditions for EPS production were different to those for optimal growth . The effect of YE on EPS production was not only due to an increase in growth but also to a direct effect on the production of EPS . The temperature played a major role . A decrease of temperature induced a slowing down of both growth and organic acids production, making the essential factors of the medium and the precursors of EPS biosynthesis more available and hence, leading to an increase in EPS production . CONCLUSION: The effects of pH, temperature and YE were determined, allowing the definition of favourable, though non-optimal, conditions for EPS production: 23 degrees C, pH 6 and 3 g l(-1) YE concentration . SIGNIFICANCE AND IMPACT OF THE STUDY: The use of a multifactorial approach for investigating the effect of fermentation conditions on EPS production has been demonstrated.

J Appl Microbiol, 2001 May, 90(5), 779 - 87
Exopolysaccharide production by Propionibacterium acidi-propionici on milk microfiltrate; Gorret N et al.; AIMS: The aims of this work were to evaluate growth and exopolysaccharide (EPS) production properties of Propionibacterium acidi-propionici DSM 4900 on milk permeate . METHODS AND RESULTS: Anaerobic growth on milk permeate was only possible if supplemented with yeast extract (YE) . Fermentation capacities of the strain were significantly improved by further increasing the supplemented YE . At 5 g l(-1) YE, consumption of 45 g l(-1) lactose to produce 9 g l(-1) biomass, 34 g l(-1) organic acids and 0.65 g l(-1) EPS was observed . From a kinetic point of view, EPS production occurred during the bacteria growth phase . At the excreted polysaccharide level, the medium showed shear-thinning behaviour with a relatively high apparent viscosity of up to 30 mPa.s (milli.Pascal.second) at a shear rate of 17 s(-1) . CONCLUSION: EPS production by P . acidi-propionici DSM 4900 on milk permeate showed promising rheological behaviour of the milk-derived medium obtained, even at a low production level . SIGNIFICANCE AND IMPACT OF THE STUDY: A kinetic study on EPS production by a food-grade bacterium that could be used in situ in alimentation was carried out.

Bioresour Technol, 2001 Jul, 78(3), 225 - 30
Utilisation of tomato pomace as a substrate for the production of vitamin B12--a preliminary appraisal; Haddadin MS et al.; The cellulose fraction in tomato pomace was hydrolysed using Trichoderma reesei, and the resultant sugars were fermented with Propionibacterium shermanii to produce vitamin B12 . A multifactorial experiment revealed that aeration of the culture of T . reesei gave substantial improvements in cellulase activity as did higher concentrations of available nitrogen, but a rapid drop in pH appeared to inhibit extensive hydrolysis; after 14 days, the maximum level of cellulose degradation was only 34.4% of the total available, and the highest level of reducing sugars achieved was 15 g l(-1) . When flasks with the latter concentration of reducing sugars were inoculated with P . shermanii, 11.1 mg l(-1) of B12 were produced under optimum conditions . If the degree of hydrolysis of the cellulose could be increased, then sufficient vitamin B12 might be generated to justify extraction but, even if purification does not prove to be economically feasible, a fermented tomato pomace (dried) with 50-55 mg kg(-1) or more of B12 could prove a useful feedstuff for animals.

Microsc Res Tech, 2001 May 15, 53(4), 288 - 97
Role of monocyte chemoattractant protein-1 in Propionibacterium acnes-induced pulmonary granulomatosis; Ichiyasu H et al.; The inflammatory process in granulomatous disorders such as sarcoidosis is mainly the consequence of delayed hypersensitivity induced by causative antigens . Propionibacterial DNA was isolated recently by PCR from human sarcoidosis tissue . Hence, we developed a model using sensitized rabbits for T cell-mediated pulmonary granulomatosis induced by Propionibacterium acnes (P . acnes) and investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of the granuloma formation in vivo . Intravenous injection of P . acnes into sensitized rabbits induced massive pulmonary granulomas on day 3 . Maximum levels of MCP-1 in sera and bronchoalveolar lavage fluid (BALF) were detected on day 1 and preceded recruitment of monocyte/macrophages and T cells . In BALF, monocyte chemotaxis peaked 1 day after P . acnes challenge, and T cell chemotaxis peaked 3 days after P . acnes challenge . Anti-MCP-1 IgG inhibited monocyte chemotaxis by 80.2% and T cell chemotaxis by 35.7% . Phenotypic analysis of migrating T cells revealed that activated and memory T cells (CD26(+)/CD45RO(+)) but not naive cells were preferentially attracted to BALF . Administration of MCP-1 antiserum in vivo inhibited the development of granulomas in both size 59.9% reduction and number 28.6% reduction, the number of infiltrating leukocytes in BALF, and the expression of adhesion molecules on leukocytes in peripheral blood and BALF . Our data indicate that MCP-1 plays important roles in granuloma formation by attracting and activating specific types of cells in this model . Furthermore, results suggest that the rabbit model resembles human angiocentric granulomatosis and would be useful for investigating the immunopathogenesis of human pulmonary granulomatosis .

Acta Crystallogr D Biol Crystallogr, 2001 May, 57(Pt 5), 706 - 8 Epub 2001 Apr 24.
Expression, crystallization and preliminary characterization of methylmalonyl coenzyme A epimerase from Propionibacterium shermanii; McCarthy AA et al.; Methylmalonyl-CoA epimerase (MMCE) is an enzyme that interconverts the R and S epimers of methylmalonyl-CoA in the pathway that links propionyl-CoA with succinyl-CoA . This is used for both biosynthetic and degradative processes, including the breakdown of odd-numbered fatty acids and some amino acids . The enzyme has been expressed in Escherichia coli both as the native enzyme and as its selenomethionine (SeMet) derivative . Crystals of both forms have been obtained by vapour diffusion using monomethylether PEG 2000 as precipitant . The native MMCE crystals are orthorhombic, with unit-cell parameters a = 56.0, b = 114.0, c = 156.0 A, and the SeMet-MMCE crystals are monoclinic, with unit-cell parameters a = 43.6, b = 78.6, c = 89.4 A, beta = 92.0 degrees; both diffract to better than 2.8 A resolution.

Appl Environ Microbiol, 2001 May, 67(5), 2235 - 9
Detection of the bacteriocin propionicin PLG-1 with polyvalent anti-PLG-1 antiserum; Leversee JA et al.; Polyclonal antibodies against the bacteriocin propionicin PLG-1 were produced in rabbits at high titer (256,000 to 512,000, as determined by indirect enzyme-linked immunosorbent assay {ELISA}) . Anti-PLG-1 antiserum neutralized the antimicrobial activity of PLG-1 preparations in a well diffusion assay . Cross-reacting protein was detected using an indirect ELISA of the culture supernatant from a fed-batch fermentation of the producer strain Propionibacterium thoenii P127 within the first 24 h of incubation, but bacteriocin activity was not detected in the same culture until 217 h of incubation . Culture supernatants from 156 strains of classical dairy propionibacteria were tested by indirect ELISA at 5 and 12 days of incubation for production of cross-reacting protein and by well diffusion assay for bacteriocin activity . Cross-reacting protein was detected in 52 strains: all of the tested strains of P . thoenii, most of the strains of Propionibacterium jensenii, and a minority of the Propionibacterium acidipropionici and Propionibacterium freudenreichii strains . Of these 52 strains, only 4 strains of P . thoenii showed bacteriocin activity in a well diffusion assay . Eight bacteriocin-negative mutants of strain P127 were negative in both ELISA and well diffusion assays . Western blot analysis showed that three protein bands bound anti-PLG-1 antibodies in culture supernatants: a 9.1-kDa band that is assumed to be the PLG-1 monomer and 16.2- and 27.5-kDa bands that may be precursors, multimers, or complexes of PLG-1.

Appl Environ Microbiol, 2001 May, 67(5), 2029 - 36
Changes in protein synthesis and morphology during acid adaptation of Propionibacterium freudenreichii; Jan G et al.; Survival of bacteria in changing environments depends on their ability to adapt to abiotic stresses . Microorganisms used in food technology face acid stress during fermentation processes . Similarly, probiotic bacteria have to survive acid stress imposed within the stomach in order to reach the intestine and play a beneficial role . Propionibacteria are used both as cheese starters and as probiotics in human alimentation . Adaptation to low pH thus constitutes a limit to their efficacy . Acid stress adaptation in the probiotic SI41 strain of Propionibacterium freudenreichii was therefore investigated . The acid tolerance response (ATR) was evidenced in a chemically defined medium . Transient exposure to pH 5 afforded protection toward acid challenge at pH 2 . Protein neosynthesis was shown to be required for optimal ATR, since chloramphenicol reduced the acquired acid tolerance . Important changes in genetic expression were observed with two-dimensional electrophoresis during adaptation . Among the up-regulated polypeptides, a biotin carboxyl carrier protein and enzymes involved in DNA synthesis and repair were identified during the early stress response, while the universal chaperonins GroEL and GroES corresponded to a later response . The beneficial effect of ATR was evident at both the physiological and morphological levels . This study constitutes a first step toward understanding the very efficient ATR described in P . freudenreichii.

Int Immunol, 2001 May, 13(5), 607 - 13
Antigen-specific T(h)1 cells as direct effectors of Propionibacterium acnes-primed lipopolysaccharide-induced hepatic injury; Okazaki T et al.; T(h)1 cells are cytotoxic effector cells that utilize Fas ligand (FasL) and tumor necrosis factor . The physiological roles of cytotoxic T(h)1 cells are considered to be immunoregulation by eliminating autoreactive lymphocytes or hyper-activated foreign antigen-specific lymphocytes . Their pathological roles, however, remain to be clarified . To investigate whether T(h)1 cells can destroy organs, we generated a Propionibacterium acnes-specific T(h)1 clone from C57BL/6 mice and tested whether the clone could serve as an effector in a P . acnes-primed lipopolysaccharide (LPS)-induced hepatic injury system, one of the septic shock models . B6SMN:C3H-FasL(gld) (B6-gld) mice, which were deficient in functional FasL, were resistant to P . acnes/LPS-induced hepatic shock . The T(h)1 clone rendered B6-gld mice sensitive to the hepatic shock after the i.v . transfer . The hepatic injury in the clone-transferred B6-gld mice, which was evaluated by both biochemical and histological examination, was inhibited by an anti-FasL mAb that we developed . These results suggested that bacterial antigen-specific T(h)1 cells like this clone can participate in organ destruction in vivo as one of the cytotoxic effectors and play a critical role in endotoxin-induced hepatic injury.

Surg Endosc . 2000 Nov;14(11):1086 . Epub 2000 Aug 29.
The role of laparoscopic biopsies in lumbar spondylodiscitis; Corpataux JM et al.; The infection of an intervertebral disk is a serious condition . The diagnosis often is elusive and difficult to make . It is imperative to have appropriate microbiologic specimens before the initiation of treatment . We report the case of a 51-year-old woman with lumbar spondylodiscitis caused by infection after the placement of an epidural catheter for postoperative analgesia . A spinal magnetic resonance imaging (MRI) scan confirmed the diagnosis, but computed tomography (CT)-guided fine-needle biopsy did not yield adequate material for a microbiologic diagnosis . Laparoscopic biopsies of the involved disk provided good specimens and a diagnosis of Propionibacterium acnes infection . We believe that this minimally invasive procedure should be performed when CT-guided fine-needle biopsy fails to yield a microbiologic diagnosis in spondylodiscitis.

Br J Dermatol, 2001 Feb, 144(2), 339 - 46
Phenotypic and genotypic characterization of antibiotic-resistant Propionibacterium acnes isolated from acne patients attending dermatology clinics in Europe, the U.S.A., Japan and Australia; Ross JI et al.; BACKGROUND: Propionibacterium acnes is the target of antimicrobial treatments for acne vulgaris . Acquired resistance to erythromycin, clindamycin and tetracyclines has been reported in strains from diverse geographical loci, but the molecular basis of resistance, via mutations in genes encoding 23S and 16S rRNA, respectively, has so far only been elucidated for isolates from the U.K . OBJECTIVES: To determine whether similar or different resistance mechanisms occur in resistant P . acnes isolates from outside the U.K . METHODS: The phenotypes and genotypes of 73 antibiotic-resistant strains of P . acnes obtained from the skin of acne patients in the U.K., U.S.A., France, Germany, Australia and Japan were compared . Antibiotic susceptibilities were determined by minimum inhibitory concentration (MIC) measurements, and polymerase chain reaction and DNA sequencing were used to identify mutations in genes encoding rRNA . RESULTS: Most erythromycin-resistant isolates (MIC(90) > or = 512 microg mL(-1)) were cross-resistant to clindamycin but at a much lower level (MIC(90) > or = 64 microg mL(-1)) . As in the U.K., resistance to erythromycin was associated with point mutations in 23S rRNA in 49 of 58 strains . An A-->G transition at Escherichia coli equivalent base 2058 was present in 24 strains . This gave a unique cross-resistance phenotype against a panel of macrolide, lincosamide and type B streptogramin antibiotics . Two further point mutations (at E . coli equivalent bases 2057 and 2059) were identified (in three and 22 isolates, respectively) and these were also associated with specific cross-resistance patterns originally identified in isolates from the U.K . However, nine of 10 erythromycin resistant-strains from Germany did not exhibit any of the three base mutations identified and, in six cases, cross-resistance patterns were atypical . Consistent with previous U.K . data, 34 of 38 tetracycline-resistant strains carried a base mutation at E . coli 16S rRNA equivalent base 1058 . Tetracycline-resistant isolates displayed varying degrees of cross-resistance to doxycycline and minocycline, but isolates from the U.S.A . had higher MICs for minocycline (4--16 microg mL(-1)) than isolates from other countries and, in particular, Australia . All the P . acnes isolates resistant to one or more of the commonly used antiacne antibiotics were sensitive to penicillin, fusidic acid, chloramphenicol and the fluoroquinolone, nadifloxacin . All but one isolate (from the U.K.) were sensitive to trimethoprim . CONCLUSIONS: This study shows that 23S and 16S mutations identified in the U.K . conferring antibiotic resistance in P . acnes are distributed widely . However, resistant strains were isolated in which mutations could not be identified, suggesting that as yet uncharacterized resistance mechanisms have evolved . This is the first report of high-level resistance to minocycline and is of concern as these strains are predicted to be clinically resistant and are unlikely to remain confined to the U.S.A . Epidemiological studies are urgently required to monitor how resistant strains are selected, how they spread and to ascertain whether the prevalence of resistance correlates with antibiotic usage patterns in the different countries.

Ann Acad Med Singapore, 2001 Jan, 30(1), 22 - 5
Antibiotic sensitivity of Propionibacterium acnes isolates from patients with acne vulgaris in a tertiary dermatological referral centre in Singapore; Tan HH et al.; OBJECTIVES: To study the minimum inhibitory concentrations (MICs) of Propionibacterium acnes (P . acnes) isolates to selected antibiotics from patients with acne vulgaris in Singapore and determine if resistance increases with prolonged use of antibiotics . DESIGN: A single-centre prospective study . SETTING: Tertiary dermatological referral centre in Singapore . PATIENTS: One hundred and fifty patients with acne vulgaris seen at the National Skin Centre . RESULTS: In patients who had never been on antibiotics, there were no resistant isolates of P . acnes . In patients who had been on short-term antibiotics (between 6 to 18 weeks), there were 2 resistant strains among the 34 isolates (6.25%); in patients who had been on antibiotics for longer periods, there were 11 resistant strains among the 51 isolates (21.6%) . The differences in the rates of isolation of resistant strains between patients who had not been on antibiotics to those that had been on long-term antibiotics were statistically significant (P = 0.015) . There was also a significant difference in isolation of resistant strains from those on short-term antibiotics compared to those who had been on long-term antibiotics (P = 0.036) . Resistance to erythromycin was most commonly encountered . Most of the erythromycin-resistant strains also showed cross-resistance to clindamycin . The average MICs to antibiotics such as minocycline, erythromycin and clindamycin in those on long-term antibiotics were significantly higher when compared to patients who had not been on antibiotics . CONCLUSIONS: Antibiotic resistance in P . acnes isolates in Singapore follows similar patterns to studies conducted in Europe . Resistance to erythromycin was most commonly seen, and this is associated with cross-resistance to clindamycin . Among the tetracycline group of drugs, the average MICs to tetracycline was higher than that for doxycycline, which in turn was higher than that for minocycline . Antibiotic resistance can occur with short-term antibiotic courses, and the rate of resistance increases as the duration of antibiotic consumption increases.

Cutis, 2001 Feb, 67(2 Suppl), 5 - 7
Are 2 combined antimicrobial mechanisms better than 1 for the treatment of acne vulgaris? Clinical and antimicrobial results of a topical combination product containing 1% clindamycin and 5% benzoyl peroxide . Introduction; Leyden J; Acne vulgaris is the most common chronic skin condition seen by dermatologists . Available topical therapies include comedolytic agents such as tretinoin, adapalene, azelaic acid, tazarotene, and salicylic acid; bactericidal agents such as benzoyl peroxide; antibiotics such as clindamycin, erythromycin, and tetracycline; and anti-inflammatory agents such as sodium sulfacetamide and metronidazole . Therapeutic failure with some antibiotic regimens due to the presence or development of resistant strains is becoming an increasing problem in the treatment of acne . One strategy aimed at limiting the resistant Propionibacterium acnes population is the use of treatment regimens that incorporate agents with complementary but different mechanisms of action . A combination gel consisting of 5% benzoyl peroxide and 1% clindamycin has recently become available . This supplement summarizes the dermatopharmacology, clinical efficacy, and tolerability of this combination gel, along with its potential role in the management of acne vulgaris.

Cutis, 2001 Feb, 67(2 Suppl), 25 - 7
Potential role for a new combination topical therapy in treating mild to moderate acne vulgaris; Tschen E; Although a variety of established topical therapies are available to treat acne, treatment success is not always achieved with current preparations . Moreover, many patients find the formulations less than fully acceptable for various reasons . A new gel that stably combines 5% benzoyl peroxide and 1% clindamycin has become available to treat mild to moderately severe inflammatory acne . There are several benefits associated with this new topical combination product: cosmetic and aesthetic acceptability to patients; limited degradation of the antibiotic by the highly reactive benzoyl peroxide component when stored according to label instructions; less irritation and drying than alcohol-based preparations; and rapid onset of action, producing a bactericidal effect after just 1 week of twice-daily use and significant clinical improvements compared with clindamycin and vehicle gels within 2 weeks . Moreover, the decreased development of antibiotic-resistant strains of Propionibacterium acnes demonstrated with the combination gel may prolong treatment efficacy.

Cutis, 2001 Feb, 67(2 Suppl), 21 - 4
The development of antibiotic resistance in Propionibacterium acnes; Leyden J et al.; Two separate studies evaluated the ability of a combination topical gel consisting of 5% benzoyl peroxide and 1% clindamycin to reduce facial Propionibacterium acnes counts in vivo and to decrease the development of resistant organisms . In the first study, the combination gel was compared with 3 topical formulations of 1% clindamycin phosphate (gel, lotion, and solution) in 80 individuals . After only 1 week of treatment, a 99.7% reduction from baseline in facial P acnes count was obtained with the combination gel . This was significantly greater (P < .001) than the 30%, 56%, or 62% reduction obtained with the clindamycin gel, lotion, or solution, respectively . After 2 weeks of treatment, the reduction from baseline P acnes counts with the combination gel was increased to 99.9%, which was again significantly greater (P < .001) than that with 1% clindamycin alone, regardless of the formulation . The second study compared the combination gel with 1% clindamycin gel in 79 patients with mild to moderate acne . After 4 weeks of treatment, the combination gel was more effective than clindamycin alone in reducing the total P acnes count, consistent with the previous study . By week 12, an increase in the number of resistant bacteria appeared in samples from patients using clindamycin alone, while counts of resistant bacteria remained stable or declined in those using the combination gel.

Hepatology, 2001 Mar, 33(3), 530 - 6
Molecular identification of bacterial 16S ribosomal RNA gene in liver tissue of primary biliary cirrhosis: is Propionibacterium acnes involved in granuloma formation?
Harada K, Tsuneyama K, Sudo Y, Masuda S, Nakanuma Y.
The etiopathogenesis of primary biliary cirrhosis (PBC) remains speculative . Epithelioid granulomas are often found in the vicinity of damaged interlobular bile ducts in PBC, raising the possibility of a reaction to microbial materials . In this study, we tried to detect and identify bacterial DNA within granulomatous lesions in PBC . Using liver sections from 9 patients with PBC and 13 control livers, granuloma in portal tracts, portal tracts without granuloma, and adjacent hepatic parenchyma were selectively microdissected from sections, and then DNA was extracted from them . First, part of the bacterial 16S ribosomal RNA (rRNA) gene was amplified from DNA samples extracted from 5 PBC and 6 control livers, and their amplicons were sequenced for the identification of bacterial species . Several indigenous bacteria were identified . Among them, Propionibacterium acnes (P . acnes) was detected as a major clone in 20% to 50% of sequenced clones from granuloma of PBC, but the detection rate of P . acnes was 0% to 20% in those cloned from adjacent hepatic parenchyma of PBC . Then, a P . acnes-specific PCR was performed using all microdissected samples . Distinct PCR products were identified in epithelioid granuloma in all 9 PBC cases . The result that P . acnes DNA is present as a major clone in granulomas of PBC, suggest that P . acnes is involved in the pathogenesis of granuloma in PBC.

Transfus Clin Biol, 2000 Dec, 7(6), 540 - 6
{Bacterial contamination of platelet concentrates by Propionibacterium acnes}; Schneider T et al.; In this study, three incidents of platelet contamination by Proprionibacterium acnes and an investigation of the transfusion process have been reported, which occurred at the Nord-Pas-de-Calais Blood Center over a period of several months . P . acnes is a bacterium that is present in the cutaneous flora; it does not produce any toxin, and is rarely considered as a pathogenic agent; its occurrence is widespread, in particular in those regions that are rich in sebum (face, back, scalp), and it is extremely apparent during adolescence . The three incidents occurred following the transfusion of a pool of leucodepleted platelet concentrates obtained from immunodeficient patients . The clinical outcome was in all cases positive . It was considered that the bacterial contamination of platelet concentrates could reflect insufficient skin disinfection at the site of the venipuncture and a minimal bacterial risk involving the blood collection procedure.

Int J Mol Med, 2001 Mar, 7(3), 321 - 7
The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats; Koyanagi T et al.; Ebselen (2-phenyl-1,2-benzoisoselenazol-3{2H}-one) is a selenoorganic compound containing selenium that has various pharmacological effects, including anti-inflammatory and antioxidant activity . Kupffer cells, residual hepatic macrophages, play an important role in the development of liver injury by producing free radicals and cytokines . The aim of this study is to evaluate whether ebselen suppresses macrophage-associated liver injury in rats . In vivo, we examined the effects of ebselen on liver injury, induced by Propionibacterium acnes and lipopolysaccharide (P . acnes-LPS), in rats where hepatic macrophages are considered to be primarily involved in injury development . Ebselen administration reduced the incidence of death following hepatic failure by P . acnes-LPS (82% vs . 20%, p<0.05) . Serum levels of alanine aminotransferase, at 5 h after LPS administration, were significantly lower in the ebselen-treated group than in the control group (202.4+/-100.3 IU/l vs . 558.4+/-146.4 IU/l, p<0.05) . Histological evidence of injury, such as necrosis, hemorrhage, and degeneration, was also suppressed by ebselen . Further, to assess the mechanisms involved, we investigated the production of cytokines and superoxide anions produced by activated hepatic macrophages in vivo . Serum levels of TNF alpha, interleukin-18 (IL-18)/IFN gamma-inducing factor (IGIF), and interferon gamma (IFN gamma) at 1 h after LPS administration were significantly lower in the ebselen-treated group . Formazan depositions, which were generated by the perfusion of the liver with nitroblue tetrazolium, were also observed less frequently in the ebselen treated group, suggesting a suppression in the release of superoxide anion from activated hepatic macrophages . In addition, we examined the effects of ebselen on cytokine production and mRNA expression, in vitro, using rat primary Kupffer cell culture . Ebselen also inhibited TNF alpha production and mRNA expression in vitro . These data imply that ebselen suppresses liver injury by inhibiting the production and/or release of proinflammatory cytokines and superoxide from activated hepatic macrophages . These data also suggest that ebselen is potent in the prevention of hepatic injury, such as endotoxemia, where hepatic macrophage activation has been implicated.

Acta Crystallogr D Biol Crystallogr, 2001 Feb, 57(Pt 2), 266 - 8
Crystallization and preliminary X-ray analysis of the 12S central subunit of transcarboxylase from Propionibacterium shermanii; Wang YF et al.; The hexameric 12S central subunit of transcarboxylase has been crystallized in both free and substrate-bound forms . The apo crystals belong to the cubic space group P4(2)32, with unit-cell parameters a = b = c = 188.5 A, and diffract to 3.5 A resolution . Crystals of two substrate-bound complexes, 12S with methylmalonyl CoA and 12S with malonyl CoA, are isomorphous and belong to space group C2, with unit-cell parameters a = 115.5, b = 201.4, c = 146.9 A, beta = 102.7 degrees . These crystals diffract to 1.9 A resolution with synchrotron radiation . Two useful heavy-atom phasing derivatives of methylmalonyl CoA-bound crystals have been obtained by co-crystallization or crystal soaking.

Mol Genet Metab, 2001 Feb, 72(2), 181 - 4
Molecular and structural analysis of two novel mutations in a patient with mut(-) methylmalonyl-CoA deficiency; Benoist JF et al.; Inherited defects in the gene encoding the methylmalonyl-CoA mutase (MCM) result in the mut forms of methylmalonic aciduria (MMA) . Twelve mutations have been identified associated with the mut(-) phenotype . We report two novel mutations (K621N and D156N) in a compound heterozygote mut(-) patient . These two mutations and three previously published ones (H627N, A191E, Y231N) were mapped onto a three-dimensional homology model of the human MCM constructed from the crystal structure of the Propionibacterium shermanii enzyme .

J Immunol, 2001 Feb 1, 166(3), 2071 - 9
Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes-induced acute lung inflammation; Itakura M et al.; Chemokine-chemokine receptor interaction plays an essential role in leukocyte/dendritic cell (DC) trafficking in inflammation and immune responses . We investigated the pathophysiological roles of secondary lymphoid tissue chemokine (SLC; CCL21) and macrophage inflammatory protein-2 (MIP-2) in the development of acute pulmonary inflammation induced by an intratracheal injection of Propionibacterium acnes in mice . Immunohistochemical studies revealed that SLC was constitutively expressed in the peribronchial areas and perivascular lymphatics in normal mice . MIP-2-positive cells were observed in alveolar spaces in mice challenged with P . acnes . Both neutralization Abs against MIP-2 and CXC chemokine receptor 2 alleviated the P . acnes-induced pulmonary inflammation when injected before P . acnes Ag challenge . On the other hand, polyclonal anti-SLC Abs (pAbs) exacerbated the pulmonary inflammation . The numbers of mature DCs (MHC class II +, CD11c+, and CD86+) as well as macrophages and neutrophils in the P . acnes Ag-challenged lungs were increased, whereas the number of CD4+ T cells, including memory T cells, was decreased . The numbers of mature and proliferating CD4+ T cells (bromodeoxyuridine(+)CD4+) in regional lymph nodes were decreased in mice injected with anti-SLC pAbs compared with those in mice treated with control Abs . An in vitro proliferation assay confirmed the impairment of the Ag-specific T cell response in regional lymph nodes of mice treated with anti-SLC pAbs . These results indicate for the first time a regulatory role for SLC-recruited mature DCs in bridging an acute inflammatory response (innate immunity) and acquired immunity in the lung.

Appl Environ Microbiol, 2001 Feb, 67(2), 499 - 503
Efficient transformation system for Propionibacterium freudenreichii based on a novel vector; Jore JP et al.; A 3.6-kb endogenous plasmid was isolated from a Propionibacterium freudenreichii strain and sequenced completely . Based on homologies with plasmids from other bacteria, notably a plasmid from Mycobacterium, a region harboring putative replicative functions was defined . Outside this region two restriction enzyme recognition sites were used for insertion of an Escherichia coli-specific replicon and an erythromycin resistance gene for selection in Propionibacterium . Hybrid vectors obtained in this way replicated in both E . coli and P . freudenreichii . Whereas electroporation of P . freudenreichii with vector DNA isolated from an E . coli transformant yielded 10 to 30 colonies per microg of DNA, use of vector DNA reisolated from a Propionibacterium transformant dramatically increased the efficiency of transformation (> or =10(8) colonies per microg of DNA) . It could be shown that restriction-modification was responsible for this effect . The high efficiency of the system described here permitted successful transformation of Propionibacterium with DNA ligation mixtures.

Surg Laparosc Endosc Percutan Tech, 2000 Dec, 10(6), 417 - 9
The role of laparoscopic biopsies in lumbar spondylodiscitis; Corpataux JM et al.; Infection of an intervertebral disk is a serious condition . Diagnosis often is elusive and difficult . It is imperative to obtain appropriate microbiological specimens before initiation of treatment . The authors describe a 51-year-old woman with lumbar spondylodiscitis that was because of infection after the placement of an epidural catheter for postoperative analgesia . A spinal magnetic resonance imaging confirmed the diagnosis, but computed tomography-guided fine needle biopsy did not provide adequate material for a microbiologic diagnosis . Laparoscopic biopsies of the involved disk provided good specimens and a diagnosis of Propionibacterium acnes infection . The authors believe that this minimally invasive procedure should be performed when computed tomography-guided fine needle biopsy does not provide a microbiologic diagnosis in spondylodiscitis.

Z Rheumatol, 2000 Oct, 59(5), 352 - 3
{Azithromycin: an anti-inflammatory effect in chronic recurrent multifocal osteomyelitis? A preliminary report}; Schilling F et al.; In this preliminary communication we report our experience with Azithromycin in patients with Chronic Recurring Multifocal Osteomyelitis (CRMO) . Seven out of 13 patients, mainly teenager, showed a fast clinical improvement after they were started on Azithromycin . The immediate therapeutic effect of Azithromycin in patients with CRMO was surprising and lead us to the hypothesis that Azithromycin could have an antiphlogistic in addition to it's antibiotic effect in this disease setting . In patients with reactive chronic pelvic osteomyelitis Azithromycin obviously had a direct influence on the sympathic coxitis . Half of the patients reported an immediate reduction of pain and a significant improvement in range of movement after they were started on Azithromycin . In all cases the clinical and radiographic signs on MRI showed a reduction of the inflammatory process . Experimental animal models have recently shown that macrolids have independent additional antiinflammatory and immunomodulatory effects . The assumed local immunomodulatory effect of Azithromycin potentially is an additional activity to the already known synergistic antimicrobial and antiinflammatory effect . Right now we are in the process of collecting data from patients with SAPHO Syndrome who underwent bone-biopsies for microbiologic and histomorphologic investigations . All patients with the growth of propionibacterium acnes were started on a long-term antibiotic therapy with Azithromycin . This study will possibly help to answer the question of the additional antiphogistic/immunomodulatory effect of Azithromycin in this disease entity and the related CRMO.

J Exp Med, 2001 Jan 1, 193(1), 35 - 49
Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease; Yoneyama H et al.; We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes-induced granulomas in mouse liver . During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas . Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associated lymphoid tissue" (PALT) . Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT . Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation . Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Appl Environ Microbiol, 2001 Jan, 67(1), 231 - 8
First evidence of lysogeny in Propionibacterium freudenreichii subsp . shermanii; Herve C et al.; Dairy propionic acid bacteria, particularly the species Propionibacterium freudenreichii, play a major role in the ripening of Swiss type cheese . Isometric and filamentous bacteriophages infecting P . freudenreichii have previously been isolated from cheese . In order to determine the origin of these bacteriophages, lysogeny of P . freudenreichii was determined by isometric bacteriophage type analysis . The genomic DNA of 76 strains were hybridized with the DNA of nine bacteriophages isolated from Swiss type cheeses, and the DNA of 25 strains exhibited strong hybridization . Three of these strains released bacteriophage particules following UV irradiation (254 nm) or treatment with low concentrations of mitomycin C . A prophage-cured derivative of P . freudenreichii was readily isolated and subsequently relysogenized . Lysogeny was therefore formally demonstrated in P . freudenreichii.

Appl Microbiol Biotechnol, 2000 Nov, 54(5), 705 - 10
Effect of glycine betaine on osmoadaptation of Propionibacterium acidipropionici cultivated in elevated osmolarities; Kylma AK et al.; The sensitivity of industrial strains Acetobacter aceti, Gluconobacter frateurii, and Propionibacterium acidipropionici to osmotic stress was studied . Growth of A . aceti and G . frateurii was totally inhibited at 0.4 M NaCl concentration, but P . acidipropionici was able to grow on a medium containing 1.2 M NaCl . Addition of glycine betaine to the medium had no detectable osmoprotective effect on A . aceti and G . frateurii cultivations in elevated NaCl concentrations, but it enabled cells of P . acidipropionici to achieve faster the maximum specific growth rate after the prolonged lag phase and therefore to gain faster the final biomass and product concentrations . The final concentrations of biomass and product of P . acidipropionici were the same as for the cultivations of the bacterium without NaCl and glycine betaine present in the medium . Intracellular accumulation of glycine betaine was detected in P . acidipropionici cells cultivated in the medium containing glycine betaine . The amount accumulated increased with NaCl concentration, suggesting that glycine betaine plays an important role in the osmoadaptation.

Dig Dis Sci, 2000 Oct, 45(10), 1996 - 2001
Preventive effect of FK 506 (tacrolimus hydrate) on experimentally induced acute liver injury in rats; Uchida K et al.; The aim of the study was to investigate the effect of the immunosuppressant FK 506 (tacrolimus hydrate) on acute liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) . Acute liver injury was induced in male Wistar rats by injecting the animals with P . acnes (10 mg/rat), and administering LPS (10 microg/rat) seven days later . One group was given FK 506 (1 mg/kg) 24 and 2 hr before administration of LPS, and the other group was given the same dose of saline . The 24-hr survival rate, serum alanine aminotransferase (ALT) concentration, and tumor necrosis factor (TNF) -alpha mRNA and protein concentrations in the liver and spleen were then compared . Hepatic macrophages were also isolated from rats seven days after P . acnes injection, LPS, and FK 506 or saline were added to the culture supernatant, and TNF-alpha production was studied . The 24-hr survival rate was 100% in the FK 506-treated group, in contrast with 16.6% in the saline group . Four hours after LPS injection, the serum ALT concentration was 755 +/- 401 in the saline group versus 119 +/- 42 units/ml (P < 0.01) in the FK 506-treated group . The serum TNF-alpha concentration was lower in the FK 506-treated group (1,419 +/- 957 pg/ml) than in the saline group (9205 +/- 2215) (P < 0.01) . The mRNA and protein concentrations in the liver and spleen in the two groups did not differ significantly 1 hr after LPS injection but were significantly lower in the FK 506-treated group after 4 hr . FK 506 did not directly inhibit TNF-alpha production by isolated cultured hepatic macrophages . FK 506 is unable to inhibit initial TNF-alpha production by hepatic macrophages (or probably that by splenic macrophages either) stimulated by injection of LPS in P . acnes + LPS-induced acute liver injury . However, the immunosuppressant does limit hepatic damage by inhibiting subsequent aggravation of inflammation by the cytokine network.

Z Rheumatol, 2000 Oct, 59(5), 352 - 3
{In Process Citation}; Schilling F et al.; In this preliminary communication we report our||| experience with Azithromycin in patients with Chronic Recurring Multifocal||| Osteomyelitis (CRMO) . Seven out of 13 patients, mainly teenager, showed a fast||| clinical improvement after they were started on Azithromycin . The immediate||| therapeutic effect of Azithromycin in patients with CRMO was surprising and||| lead us to the hypothesis that Azithromycin could have an antiphlogistic in||| addition to it's antibiotic effect in this disease setting . In patients with||| reactive chronic pelvic osteomyelitis Azithromycin obviously had a direct||| influence on the sympathic coxitis . Half of the patients reported an immediate||| reduction of pain and a significant improvement in range of movement after they||| were started on Azithromycin . In all cases the clinical and radiographic signs||| on MRI showed a reduction of the inflammatory process . Experimental animal||| models have recently shown that macrolids have independent additional||| antiinflammatory and immunomodulatory effects . The assumed local||| immunomodulatory effect of Azithromycin potentially is an additional activity||| to the already known synergistic antimicrobial and antiinflammatory effect.||| Right now we are in the process of collecting data from patients with SAPHO||| Syndrome who underwent bone-biopsies for microbiologic and histomorphologic||| investigations . All patients with the growth of propionibacterium acnes were||| started on a long-term antibiotic therapy with Azithromycin . This study will||| possibly help to answer the question of the additional||| antiphogistic/immunomodulatory effect of Azithromycin in this disease entity||| and the related CRMO.

J Dermatol, 2000 Oct, 27(10), 635 - 8
Relationship between Propionibacterium acnes biotypes and Jumi-haidoku-to; Higaki S et al.; We examined the relationship between Propionibacterium acnes biotypes and Jumi-haidoku-to (JHT) . In all the P . acnes strains tested, the production of propionic acid (PA) and butyric acid (BA) was suppressed in a medium containing 1 mg/ml JHT compared with the control medium without JHT . There were no significant differences in the rates of decreased PA and BA production between P . acnes biotype 3 (B3) and the other biotypes or between isolates from mild skin rash and more severe skin rash . P . acnes B3 was the most commonly identified biotype . The clinical effects on acne due to the anti-P . acnes lipase activity of JHT did not seem to be influenced by the degree of acne rash or the P . acnes biotype.

Biochem, Eng . J. . 2000 Dec 1, 6(3), 207 - 214
Improvement of vitamin B(12) fermentation by reducing the inhibitory metabolites by cell recycle system and a mixed culture; Miyano K et al.; The major problem in vitamin B(12) production using Propionibacterium is the growth inhibition of the cell due to the accumulation of inhibitory metabolites such as propionic acid and acetic acid . In the present paper, we considered several approaches of controlling the propionic acid concentration at low level . Namely: (1) the periodic cultivation of Propionibacterium where dissolved oxygen (DO) concentration was alternatively changed between 0 and 1ppm; (2) cell recycle system using hollow fiber module; and (3) mixed culture using Propionibacterium and Ralstonia eutropha where the latter microorganism assimilates the propionic acid produced by the former . It was found that the productivity of vitamin B(12) was the highest for the cell recycle system, while if the performance was evaluated based on the amount of vitamin B(12) produced per medium used, the mixed culture system gave the far highest value.

Sci Prog, 2000, 83 ( Pt 3), 277 - 301
Physiological peculiarities of propionibacteria--present facts and prospective applications; Vorobjeva L; The genus Propionibacterium includes dairy and cutaneous propionibacteria; they differ principally by their natural habitats: in milks, cheeses and on human skin and in the rumen ruminants respectively . Using modern methods of molecular biology a new composition of the genus, containing at present 10 species was established . These bacteria generate energy by fermentation, which is linked with a short anaerobic respiration chain yielding more ATP than in any other bacterial fermentation . Propionibacteria contain the apparatus for the aerobic lifestyle including antioxidative defense systems consisting of SOD, catalase and peroxidase . The metabolism of "anaerobic" species of propionic acid bacteria (PAB) is tuned to the use of a high level of vitamin B12, which participates not only in fermentation, but in a number of vital anabolic reactions too . In the absence of vitamin B12, PAB switch to a B12-independent way of existence, which is, however, less effective than the B12-dependent one . Cells, culture liquids (CL) and cell extracts possess antimutagenic (AM) activity . AM activity of CL is linked with an extracellular protein(s) . The proteinaceous cytosolic fraction of propionibacteria exerts reactivative activity on pro- and eukaryotic organisms subjected to different and unrelated stresses . The physiological peculiarities of PAB open up new areas of their practical applications: the possibility of creation of medical and prophylactic preparations with AM and antistress properties, preparations with antioxidative properties, SOD and of human probiotics that may be useful in the biotechnology of environmental health.

J Vet Med B Infect Dis Vet Public Health, 2000 Oct, 47(8), 619 - 27
In vitro and in vivo effects of an immunomodulator composed of Escherichia coli lipopolysaccharide and Propionibacterium granulosum-inactivated cells in pigs; Pappaterra Mendoza GJ et al.; The in vitro cytokine profiles of porcine alveolar macrophages and peripheral blood mononuclear cells (PBMC) were examined by reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay after stimulation with the immunomodulatory compound INMD {lipopolysaccharide (LPS) and Propionibacterium granulosum} . Expression of interleukin-1 (IL-1), IL-6, IL-12 and tumour necrosis factor-alpha (TNF-alpha), but not of IL-10, was detected in INMD-stimulated alveolar macrophages . Stimulated PBMC expressed IL-1, IL-2, IL-4, IL-6, IL-10 and IL-12 and secreted interferon-gamma (IFN-gamma) . In all cases, the level of response was lower with INMD than with E . coli LPS alone, except for IFN-gamma, which was secreted in higher levels in INMD-stimulated cells . In a second experiment, the ex vivo effect of the administration of INMD was evaluated using the product as a coadjuvant of a live attenuated Aujeszky's disease virus (ADV) vaccine . For this purpose, 85 8-10-week-old crossbred pigs were assigned to two groups (group A = 43 and group B = 42) and vaccinated with ADV . Group B received, simultaneously with the first dose of vaccine, an intramuscular dose of INMD equivalent to 20 micrograms/ml LPS and 250 micrograms/ml P . granulosum, while group A was given sterile saline solution as a placebo . At the time of vaccination, 97.6% (42 of 43) and 95.2% (40 of 42) of animals of groups A and B, respectively, had anti-gB maternal antibodies . Of those animals, anti-gE ADV antibodies were detected in 11.6% of animals of group A (five of 43) and 19% of group B (eight of 42) . All animals were boosted with ADV vaccine alone 4 weeks later . Pigs to which INMD was administered together with the vaccine showed higher primary humoral responses than the vaccine-alone animals (P < 0.005) . However, after boosting significant differences disappeared (P > 0.05).

Appl Environ Microbiol, 2000 Nov, 66(11), 4688 - 95
Characterization of pRGO1, a plasmid from Propionibacterium acidipropionici, and its use for development of a host-vector system in propionibacteria; Kiatpapan P et al.; The complete nucleotide sequence of pRGO1, a cryptic plasmid from Propionibacterium acidipropionici E214, was determined . pRGO1 is 6, 868 bp long, and its G+C content is 65.0% . Frame analysis of the sequence revealed six open reading frames, which were designated Orf1 to Orf6 . The deduced amino acid sequences of Orf1 and Orf2 showed extensive similarities to an initiator of plasmid replication, the Rep protein, of various plasmids of gram-positive bacteria . The amino acid sequence of the putative translation product of orf3 exhibited a high degree of similarity to the amino acid sequences of DNA invertase in several bacteria . For the putative translation products of orf4, orf5, and orf6, on the other hand, no homologous sequences were found . The function of these open reading frames was studied by deletion analysis . A shuttle vector, pPK705, was constructed for shuttling between Escherichia coli and a Propionibacterium strain containing orf1 (repA), orf2 (repB), orf5, and orf6 from pRGO1, pUC18, and the hygromycin B-resistant gene as a drug marker . Shuttle vector pPK705 successfully transformed Propionibacterium freudenreichii subsp . shermanii IFO12426 by electroporation at an efficiency of 8 x 10(6) CFU/microg of DNA under optimized conditions . Transformation of various species of propionibacteria with pPK705 was also performed at efficiencies of about 10(4) to 10(7) CFU/microg of DNA . The vector was stably maintained in strains of P . freudenreichii subsp . shermanii, P . freudenreichii, P . pentosaceum, and P . freudenreichii subsp . freudenreichii grown under nonselective conditions . Successful manipulation of a host-vector system in propionibacteria should facilitate genetic studies and lead to creation of genes that are useful industrially.

Sarcoidosis Vasc Diffuse Lung Dis, 2000 Oct, 17(3), 256 - 65
Proliferative response of peripheral blood mononuclear cells and levels of antibody to recombinant protein from Propionibacterium acnes DNA expression library in Japanese patients with sarcoidosis; Ebe Y et al.; BACKGROUND AND AIM OF THE WORK: The causes of sarcoidosis are unknown . Propionibacterium acnes has been isolated from sarcoid lesions, and many genomes of P . acnes or P . granulosum have been detected in all biopsy samples tested from Japanese patients with sarcoidosis . We searched for protein antigens from propionibacteria that caused immune responses in patients with sarcoidosis but not in subjects without sarcoidosis . METHODS: A lambda gt11 genomic DNA expression library of P . acnes was screened with sera from patients with sarcoidosis . Antibodies to a recombinant protein from the insert recovered by the screening were measured in serum and bronchoalveolar lavage (BAL) fluid from patients with or without sarcoidosis by an immunofluorescence-based method . Peripheral blood mononuclear cells from patients with and without sarcoidosis were used to examine the lymphoproliferative response to the protein . RESULTS: Of 180,000 plaques screened, two clones coded for an identical recombinant protein, termed RP35, were recognized by sera . RP35 was the C-terminal region of P . acnes trigger factor . RP35 caused sarcoidosis specific proliferation of the mononuclear cells from 9 (18%) of the 50 patients with sarcoidosis; in a similar way, purified protein derived from Mycobacterium tuberculosis evoked specific responses in 8 (38%) of 21 patients with tuberculosis . Serum levels of IgG and IgA antibodies to RP35 were high in patients with sarcoidosis and other lung diseases . In BAL fluid levels IgG or IgA antibodies were high in 7 (18%) and 15 (39%), respectively, of 38 patients with sarcoidosis, and in 2 (3%) and 2 (3%), respectively, of 63 patients with other lung diseases . CONCLUSIONS: The RP35 protein from P . acnes causes a cellular immune response in some patients with sarcoidosis but not in subjects without sarcoidosis.

FEMS Microbiol Lett, 2000 Oct 15, 191(2), 183 - 6
Heat shock proteins and inflammatory acne vulgaris: molecular cloning, overexpression and purification of a propionibacterium acnes GroEL and DnaK homologue; Farrar MD et al.; Propionibacterium acnes is associated with inflammatory acne . The genes encoding two putative mediators of inflammation, the heat shock proteins GroEL and DnaK, were cloned from this organism and sequenced . groEL and dnaK encode proteins of 56.8 and 66.4 kDa, respectively, which show a high degree of homology (>75% similarity) to the GroEL and DnaK proteins of mycobacteria and streptomycetes . The promoter regions of both genes contain inverted repeat sequences believed to be involved in the transcriptional regulation of heat shock genes . Recombinant P . acnes GroEL and DnaK were overexpressed in Escherichia coli with C-terminal histidine tags . The recombinant proteins were purified from E . coli by metal affinity chromatography . These proteins will now be used in immunological investigations to determine their role in inflammatory acne.

J Gastroenterol, 2000, 35(9), 696 - 701
Increased expression of osteopontin in activated Kupffer cells and hepatic macrophages during macrophage migration in Propionibacterium acnes-treated rat liver; Wang Y et al.; Osteopontin is an extracellular matrix component that can act as a chemokine to induce macrophage migration . The significance of osteopontin in macrophage infiltration into the liver was examined in rats given heat-killed Propionibacterium acnes . In normal rats, osteopontin mRNA expression in the liver was minimal, determined by quantitative-competitive reverse transcription-polymerase chain reaction (RT-PCR) assay . Northern blot analysis revealed that osteopontin mRNA was not expressed in Kupffer cells isolated from normal rats . When rats received heat-killed P . acnes intravenously, marked macrophage accumulation, forming granulomas, developed in the liver later than 3 days after the injection and its extent became maximal between 5 and 7 days . In these rats, osteopontin mRNA expression was increased in the liver later than 1 day (with its peak at 3 days after the injection), and the mRNA expression was increased markedly in Kupffer cells and hepatic macrophages isolated at 7 days . The mRNA expression of monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), chemokines for monocytes and macrophages, was also increased in the liver of P . acnes-treated rats, with peak expression at 3 days . We conclude that osteopontin derived from Kupffer cells and hepatic macrophages may contribute to the infiltration of monocytes and macrophages into the liver cooperatively with the actions of MCP-1 and MIP-1alpha in P . acnes-treated rats.

J Cutan Med Surg, 2000 Jul, 4(3), 138 - 41
Effects of benzoyl peroxide on lipogenesis in sebaceous glands using an animal model; Burkhart CG et al.; BACKGROUND: Benzoyl peroxide is the most widely used topical agent for acne since the 1960s . Concomitant treatment of benzoyl peroxide with oral, or topical antibiotics diminishes the multiplication of antibiotic-resistant strains of Propionibacteria acnes . Besides being antibacterial, the chemical also functions as a peeling agent, has comedolytic activity, reduces free fatty acid levels, and is touted to be sebosuppressive . OBJECTIVE: The purpose was to determine the ability of topically applied benzoyl peroxide to suppress lipogenesis of the sebaceous glands . METHODS: The data were obtained employing an animal model for human sebaceous glands, namely, the flank organs of female golden Syrian hamsters . RESULTS: Our results reveal no inhibition of lipogenesis in sebaceous glands by topical application of benzoyl peroxide . CONCLUSION: Despite many functions beneficial in acne therapy, benzoyl peroxide does not possess sebosuppressive capabilities . With the advent of water-soluble organic peroxides revealing similar antimicrobial activity to benzoyl peroxide, all therapeutic parameters (save for sebosuppression) will need to be assessed to weigh the benefits of these second-generation acne-fighting peroxides.

J Dermatol, 2000 Aug, 27(8), 519 - 22
Correlation between Propionibacterium acnes biotypes, lipase activity and rash degree in acne patients; Higaki S et al.; We examined the possible correlation between biotypes of Propionibacterium acnes, lipase activity, and rash degree in acne patients . Among 5 P . acnes biotypes, P . acnes biotype 3 (B3) was the most common, followed by P . acnes biotypes 1, 2 and 4; P . acnes biotype 5 was not found . P . acnes B3 was isolated from more severe skin rashes than those of the other biotypes . Production of propionic acid (PA) and butyric acid (BA) by P . acnes B3 was higher than those by the other P . acnes biotypes . As the rash degree in acne patients was more severe, the production of PA and BA elevated . Although only a few P . acnes strains were examined in the present study, P . acnes B3 had the highest lipase activity and might have the greatest influence on skin rash in acne patients.

J Food Prot, 2000 Sep, 63(9), 1214 - 21
Viability and beta-galactosidase activity of dairy propionibacteria subjected to digestion by artificial gastric and intestinal fluids; Zarate G et al.; An important criterion to consider in the selection of strains for dietary adjuncts is the ability of the microorganisms to survive the severe conditions of acidity and bile concentrations usually found in the gastrointestinal tract . In the present work, we report the effects of digestions by artificial gastric and intestinal fluids on beta-galactosidase activity and survival of four strains of dairy propionibacteria previously selected by their bile tolerance and beta-galactosidase activity . The strains were exposed to artificial gastric juice at pH values between 2 and 7 and then subjected to artificial intestinal digestion . Both viability and beta-galactosidase activity were seriously affected at pH 2 . Skim milk and Emmental cheese juice exerted a protective effect on the parameters tested . The trypsin present in the intestinal fluid inactivated the enzyme beta-galactosidase in strains of Propionibacterium freudenreichii but not in Propionibacterium acidipropionici . Moreover, the presence of bile salts enhanced the beta-galactosidase activity of these strains by permeabilization of the cells during the first hour of exposure . The intestinal transit rate confirmed the permanence of the bacteria in the intestine for long enough to be permeabilized . These results suggest that P . acidipropionici would be a good source of beta-galactosidase activity in the intestine . We also propose a practical and effective in vitro method as a tool of screening and selection of potential probiotic bacteria.

J Immunol, 2000 Sep 15, 165(6), 3317 - 23
Nitric oxide is neither necessary nor sufficient for resolution of Plasmodium chabaudi malaria in mice; van der Heyde HC et al.; Malaria is a life-threatening re-emerging disease, yet it is still not clear how bloodstage malarial parasites are killed . Nitric oxide (NO), which has potent anti-microbial activity, may represent an important killing mechanism . The production of NO during descending Plasmodium chabaudi parasitemia, a period when parasites are killed by the immune response, supports this concept . However, NOS20/0 and NOS30/0 mice as well as mice treated with NO synthase 2 (NOS2) inhibitors do not develop exacerbated malaria, indicating that NO production is not necessary for the suppression of P . chabaudi parasitemia . It is possible due to the plasticity in the immune response during malaria that Ab-mediated immunity is enhanced in the absence of NO, thereby explaining the lack of exacerbated malaria in NOS-deficient mice even though NO may function in protection . However, NOS2- and B cell-deficient mice, which cannot use Ab-mediated immunity, suppress their parasitemia with a similar time course as B cell-deficient controls . C57BL/6 mice treated with Propionibacterium acnes to elicit high levels of macrophage-derived NO have a similar time course of P . chabaudi parasitemia as P . acnes-treated NOS20/0 mice, which do not produce NO; this indicates that NO is not sufficient for parasite killing . Collectively, these results indicate that NO is not necessary or sufficient to resolve P . chabaudi malaria.

Ceska Slov Farm, 2000 Mar, 49(2), 62 - 7
{Effective and safe pharmacotherapy of acne vulgaris and treatment of sun-damaged skin}; Fendrich Z et al.; An inevitable condition for the pharmacist is a basic knowledge of dermatological changes which are prominent in acne and solar impairment of the skin to be able to recommend in a qualified manner an effective and safe treatment to the patient . However, sufferers of the more serious forms of acne should always be referred to their general practitioner, or preferentially a dermatologist . Acne vulgaris is an androgen-induced disorder, but three major mechanisms for the development of the disease have been identified: hypertrophy of the sebaceous gland, hyperkatosis of the follicular epithelium, and proliferation of microbial flora, particularly Propionibacterium acnes . The basis of all lesions is the microcomedone which is developed into the ripe comedone . Inflammatory lesions are thought to be due to proliferation of P . acnes . In the selfmedication of common acne, benzoyl peroxide, which in a 5-10% lotion exerts antimicrobial and keratolytic properties, proved to be useful . Patients appreciate a lot its instant effect which is visible after just one day of treatment . Salicylic acid is another effective drug, which, when used on the long-term basis, has comedolytic properties; it reduces the number of microcomedones and counteracts plugging of the follicles . In addition, in healthy young women who take oral contraception, a triphasic combined oral preparations of contraceptives with newer progestins, notably with norgestimmate, which is practically free of androgenic effects, are recommended with advantage for the treatment of moderate acne vulgaris without any adverse effects . Solar impairment of the skin, the so-called solar ageing, is clinically indistinguishable from biological ageing . Changes connected with solar impairment appear mostly in the dermis, where solar elastosis develops, the skin gets drier and wrinkle formation appears . For the treatment, hydroxy acids are recommended, namely salicylic acid, which is very effective, because in combination with a suitable vehicle it produces desquamation or exfoliation . Desquamation is beneficial as it gives a youthful appearance to the skin.

J Cataract Refract Surg, 2000 Jul, 26(7), 1085 - 8
Propionibacterium acnes endophthalmitis requiring intraocular lens removal after failure of medical therapy; Teichmann KD; A 52-year-old Saudi man developed intraocular inflammation 7 weeks after uneventful phacoemulsification with implantation of a silicone posterior chamber intraocular lens (IOL) . Cultures from the aqueous and vitreous were repeatedly negative, but a temporary response to intracameral and intravitreal injection of vancomycin was noted . A series of 6 intraocular injections given over 5 days failed to resolve the inflammation . It did, however, disappear after the IOL was removed . The IOL provided the only positive culture in this case of Propionibacterium acnes endophthalmitis . Nine months later, a posterior chamber poly(methyl methacrylate) IOL was implanted . Eighteen months later, the patient had no recurrences . He regained a visual acuity of 20/30, corresponding to his best postoperative result.

Metab Eng, 1999 Oct, 1(4), 309 - 19
In vivo 13C NMR study of the bidirectional reactions of the Wood-Werkman cycle and around the pyruvate node in Propionibacterium freudenreichii subsp . shermanii and Propionibacterium acidipropionici; Deborde C et al.; This study used in vitro 13C NMR spectroscopy to directly examine bidirectional reactions of the Wood-Werkman cycle involved in central carbon metabolic pathways of dairy propionibacteria during pyruvate catabolism . The flow of {2-13C}pyruvate label was monitored on living cell suspensions of Propionibacterium freudenreichii subsp . shermanii and Propionibacterium acidipropionici under acidic conditions . P . shermanii and P . acidipropionici cells consumed pyruvate at apparent initial rates of 161 and 39 micromol min(-1) g(-1) (cell dry weight), respectively . The bidirectionality of reactions in the first part of the Wood-Werkman cycle was evident from the formation of intermediates such as {3-13C}pyruvate and {3-13C}malate and of products like {2-13C}acetate from {2-13C}pyruvate . For the first time alanine labeled on C2 and C3 and aspartate labeled on C2 and C3 were observed during {2-13C}pyruvate metabolism by propionibacteria . The kinetics of aspartate isotopic enrichment was evidence for its production from oxaloacetate via aspartate aminotransferase . Activities of a partial tricarboxylic acid pathway, acetate synthesis, succinate synthesis, gluconeogenesis, aspartate synthesis, and alanine synthesis pathways were evident from the experimental results.

Cornea, 2000 Jul, 19(4), 451 - 4
Propionibacterium acnes as a cause of visually significant corneal ulcers; Underdahl JP et al.; PURPOSE: To report Propionibacterium acnes as a cause of vision-threatening infectious keratitis and to discuss culture isolation and antibiotic treatment . METHODS: Retrospective case series presentation collected from three academic medical centers . RESULTS: Six cases of P . acnes infectious keratitis are presented, all of which were associated with a compromised corneal barrier or environment . All cases were culture-positive on thioglycolate broth; none became positive before 7 days of growth . No other organisms were isolated from any culture, and the growth of P . acnes occurred in some cases despite negative gram stains . CONCLUSION: P . acnes can produce vision-debilitating keratitis when the cornea is compromised . Growth in culture should be monitored for at least 10 days to ensure isolation of this fastidious organism . P . acnes may respond to several different antibiotics that have gram-positive coverage, but it should be treated with vancomycin to enhance clearance of the organism.

Rev Med Interne, 2000 Jun, 21(6), 547 - 9
{Infectious osteoarthritis due to Propionibacterium acnes . Two new cases}; Hustache-Mathieu L et al.; INTRODUCTION: Propionibacterium acnes is an anaerobic germ, usually found as a saprophyte of the skin and the mucosa . It may be responsible for iatrogenic or spontaneous osteoarhritis . EXEGESIS: We report two new cases of septic arthritis induced by P . acnes: a case of iatrogenic spondylodiscitis and a case of spontaneous septic arthritis of the lumbar facet joints . The two patients were immunocompetent, without acne . CONCLUSION: Except for patients with criteria of the SAPHO syndrome (synovitis-acne-pustulosis-hyperostosis-osteomyelitis), osteoarthritis caused by P . acnes is increasingly described . The number of these infections is probably underestimated because of the technical problems involved in isolating P . acnes in the laboratory.

J Am Acad Dermatol, 2000 Aug, 43(2 Pt 3), S47 - 50
Combination azelaic acid therapy for acne vulgaris; Webster G; There is no topical antiacne medication that acts against all four of the major pathophysiologic features of acne: hyperkeratinization, sebum production, bacterial proliferation, and inflammation . Topical azelaic acid cream helps both to normalize keratinization and to reduce the proliferation of Propionibacterium acnes, and has proven to be effective against both noninflammatory and inflammatory lesions . The results of a recent study now demonstrate that its efficacy can be enhanced, and patient ratings of overall impression improved, when it is used in combination with other topical medications such as benzoyl peroxide 4% gel, clindamycin 1% gel, tretinoin 0.025% cream, and erythromycin 3%/benzoyl peroxide 5% gel . Furthermore, another study has shown that azelaic acid plus benzoyl peroxide achieves greater efficacy and higher patient ratings of convenience than monotherapy with erythromycin-benzoyl peroxide gel.

J Immunol, 2000 Jul 15, 165(2), 997 - 1003
Skin-specific caspase-1-transgenic mice show cutaneous apoptosis and pre-endotoxin shock condition with a high serum level of IL-18; Yamanaka K et al.; To study the pathophysiological roles of overexpressed caspase-1 (CASP1), originally designated as IL-1 beta-converting enzyme, we generated transgenic mice in which human CASP1 is overexpressed in their keratinocytes . The transgenic mice spontaneously developed recalcitrant dermatitis and skin ulcers, characterized by the presence of massive keratinocyte apoptosis . The skin of the mice contained the active form of human CASP1 and expressed mRNA for caspase-activated DNase, an effector endonuclease responsible for DNA fragmentation . Their skin and sera showed elevated levels of mature IL-18 and IL-1 beta, but not of IFN-gamma . The plasma from these animals induced IFN-gamma production by IL-18-responsive NK cells . Administration of heat-killed Propionibacterium acnes, a potent in vivo type 1 cell inducer, caused IFN-gamma-mediated lethal liver injury in the transgenic mice, which was completely inhibited by treatment with neutralizing anti-IL-18 Ab . These results indicated that in vivo overexpression of CASP1 caused spontaneous apoptotic tissue injury and rendered mice highly susceptible to exogenous type 1 cell-inducing condition in collaboration with endogenously accumulated proinflammatory cytokines.

J Pharm Pharmacol, 2000 May, 52(5), 531 - 8
Effects of ZNC-2381, a new oral compound, on several hepatic injury models and on hepatocellular apoptosis in mice and rats; Itokazu Y et al.; The hepatoprotective effect of ZNC-2381 (1-(4-aminophenyl) methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo{4,5-b}pyridine-2-one), a novel 2-one dihydroimidazopyridine derivative, has been evaluated in several experimental models of hepatic injury . In mice, oral ZNC-2381, administered at doses of 3, 10 or 30 mgkg(-1), 1 h before induction of hepatic injury with concanavalin A, dose-dependently inhibited increases in serum alanine aminotransferase (ALT) activity . Apoptosis of liver cells, as indicated by DNA fragmentation (nucleosome assay) and DNA-ladder formation (electrophoresis), was also inhibited dose-dependently . ZNC-2381 dose-dependently inhibited concanavalin A-induced increases in serum tumour necrosis factor (TNF)-alpha levels, and TNF-alpha mRNA expression in the liver . Oral ZNC-2381 also dose-dependently inhibited increases in serum ALT activity in mice with hepatic injury induced by Propionibacterium acnes and a bacterial lipopolysaccharide (LPS) or D-galactosamine-LPS, and in rats with D-galactosamine-induced hepatic injury . These results indicate that oral ZNC-2381 inhibits cytokine (TNF-alpha) production and cytokine-related hepatocellular apoptosis, and might thus prevent different types of hepatic injury.

Aust Vet J, 2000 Mar, 78(3), 175 - 8
Novel Propionibacterium infection in cattle; Forbes-Faulkner JC et al.; OBJECTIVE: To describe four cases of infection in cattle, from geographically different places, with a presumptive new species of Propionibacterium, which causes granulomatous lesions in the head, thorax, abdomen, pelvic area and skin . PROCEDURE: Gross lesions, ranging from 0.5 to 15 cm and detected during routine carcase inspection at the abattoir, were submitted to the laboratory for routine testing in the National Granuloma Submission Program . The bacterium isolated was identified using morphological characteristics, biochemical reactions, cell wall components, products of fermentation and 16S rRNA gene sequencing . RESULTS: Gross lesions submitted for examination consisted of a fibrous outer capsule enclosing thick yellow pus-like material . A Gram-Glynn stain of the histological sections revealed colonies of Gram-positive, filamentous, branching bacteria . Bacteriological culture, cell wall analysis, biochemical reactions and 16S rRNA sequencing identified the organism as a Propionibacterium sp closely related to P cyclohexanicum and the P freudenreichii cluster . CONCLUSION: This is the first report of a Propionibacterium sp closely related to P cyclohexanicum and the P freudenreichii cluster associated with extensive granulomatous lesions in cattle in Queensland . Sequencing data are suggestive of a previously undescribed species of the Propionibacterium genus.

Am J Ophthalmol, 2000 May, 129(5), 571 - 6
Corneal biopsy in the management of progressive microbial keratitis; Alexandrakis G et al.; PURPOSE: To study the indications and role of diagnostic corneal biopsy in the management of patients with progressive microbial keratitis . METHODS: The records of 33 consecutive patients who underwent a diagnostic corneal biopsy from January 1, 1986, to December 31, 1998, were reviewed . The indication for corneal biopsy was progressive infectious keratitis despite intensive broad-spectrum topical antimicrobial therapy, or progressive stromal infiltration inaccessible to corneal scrapings . Microbiologic evaluation of all corneal biopsies was performed, and 11 of the 33 biopsies were also examined histopathologically . RESULTS: A microorganism was isolated from 27 (82%) of the 33 corneal biopsies . Of the six patients with a negative biopsy, a penetrating keratoplasty was performed in five patients and the pathogen was identified by examination of the corneal button . In one patient no microorganism was identified; however, the infection resolved with topical antimicrobial therapy . The most common risk factor for keratitis was foreign body exposure or corneal abrasion (14 patients) . A solid stromal infiltrate was the most common pattern of corneal involvement . Corneal biopsy revealed previously unidentified microorganisms that led to a change in antimicrobial therapy in 24 (89%) of the 27 patients and confirmed prior culture results in the remaining 3 patients . Microbiologic evaluation of the corneal biopsy was more sensitive than histopathologic examination . Acanthamoeba was the most commonly isolated pathogen (five cases), followed by Propionibacterium acnes and Fusarium (four cases each) . Gram-positive organisms were isolated in 16 patients . Only five of the 27 patients with a positive corneal biopsy required a penetrating keratoplasty, in contrast to five of the six patients with a negative corneal biopsy (P =.005) . During the 13-year period of the study, only three corneal biopsies were performed in the last 6 years . CONCLUSIONS: Microbiologic evaluation of a diagnostic corneal biopsy contributed significantly to the diagnosis, treatment, and outcome of patients with progressive infectious keratitis.

Eur J Biochem, 2000 Jun, 267(12), 3487 - 95
Crystal structure of cambialistic superoxide dismutase from porphyromonas gingivalis; Sugio S et al.; The crystal structure of cambialistic superoxide dismutase (SOD) from Porphyromonas gingivalis, which exhibits full activity with either Fe or Mn at the active site, has been determined at 1.8-A resolution by molecular replacement and refined to a crystallographic R factor of 17.9% (Rfree 22.3%) . The crystals belong to the space group P212121 (a = 75.5 A, b = 102.7 A, c = 99.6 A) with four identical subunits in the asymmetric unit . Each pair of subunits forms a compact dimer, but not a tetramer, with 222 point symmetry . Each subunit has 191 amino-acid residues most of which are visible in electron density maps, and consists of seven alpha helices and one three-stranded antiparallel beta sheet . The metal ion, a 3 : 1 mixture of Fe and Mn, is coordinated with five ligands (His27, His74, His161, Asp157, and water) arranged at the vertices of a trigonal bipyramid . Although the overall structural features, including the metal coordination geometry, are similar to those found in other single-metal containing SODs, P . gingivalis SOD more closely resembles the dimeric Fe-SODs from Escherichia coli rather than another cambialistic SOD from Propionibacterium shermanii, which itself is rather similar to other tetrameric SODs.

Int J Syst Evol Microbiol, 2000 Jan, 50 Pt 1, 191 - 9
Hongia gen . nov., a new genus of the order Actinomycetales; Lee SD et al.; An aerobic, nocardioform actinomycete, named LM 161T, was isolated from a soil sample obtained from a gold mine in Kongiu, Republic of Korea . This organism formed well-differentiated aerial and substrate mycelia and produced branched hyphae that fragmented into short or elongated rods . The cell wall contains major amounts of LL-diaminopimelic acid, alanine, glycine, glutamic acid, mannose, glucose, galactose, ribose and acetyl muramic acid . The major phospholipids of this isolate are phosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol, and the major isoprenologue is a tetrahydrogenated menaquinone with nine isoprene units . The whole-cell hydrolysate of strain LM 161T contains 12-methyltetradecanoic and 14-methylpentadecanoic acids as the predominant fatty acids, but does not contain mycolic acids . The G+C content of the DNA is 71.3 mol% . The phylogenetic position of the test strain was investigated using an almost complete 16S rDNA sequence . The isolate formed the deepest branch in the clade encompassing the members of the suborder Propionibacterineae Rainey et al . 1997 . On the basis of chemical, phenotypic and genealogical data, it is proposed that this isolate be classified within a new genus as Hongia koreensis gen . nov., sp . nov . in the order Actinomycetales . The type strain is LM 161T (= IMSNU 50530T).

Int J Syst Evol Microbiol, 2000 Jan, 50 Pt 1, 179 - 81
Luteococcus peritonei sp . nov., isolated from the human peritoneum; Collins MD et al.; An unusual catalase-positive pleomorphic Gram-positive rod isolated from a human clinical specimen was subjected to a polyphasic taxonomic analysis . Comparative 16S rRNA gene sequence analysis revealed the unknown bacterium was a member of the high G+C branch of the Gram-positive bacteria (Actinobacteria), and was phylogenetically a member of the family Propionibacteriaceae, with Luteococcus japonicus as its nearest relative . Based on both phenotypic and phylogenetic evidence, it is proposed that the unknown bacterium be classified in the genus Luteococcus, as Luteococcus peritonei sp . nov . The type strain of Luteococcus peritonei is CCUG 38120T.

Immunol Rev, 2000 Apr, 174, 192 - 209
Pathophysiological roles of interleukin-18 in inflammatory liver diseases; Tsutsui H et al.; Innate immune response to microbes sometimes determines the nature of the following specific immune response . Kupffer cells, a potent constituent of innate immunity, play a key role in developing the type 1 immune response by interleukin (IL)-12 production . Furthermore, Kupffer cells have the potential to induce liver injury by production of IL-18 . Propionibacterium acnes-primed lipopolysaccharide (LPS)-challenged liver injury is the prototype of IL-18-induced tissue injury, in which IL-18 acts on natural killer cells to increase Fas ligand (FasL) that causes liver injury by induction of Fas-dependent hepatocyte apoptosis . LPS induces IL-18 secretion from Kupffer cells in a caspase-1-dependent manner . Indeed, caspase-1-deficient mice are resistant to P . acnes and LPS-induced liver injury . However, administration of soluble FasL induces acute liver injury in P . acnes-primed caspase-1-deficient mice but does not do so in IL-18-deficient mice, indicating that IL-18 release in a caspase-1-independent fashion is essential for this liver injury . Therefore, a positive feedback loop between FasL and IL-18 plays an important role in the pathogenesis of endotoxin-induced liver injury.

Cytokine, 2000 Apr, 12(4), 299 - 308
Liver-infiltrating T lymphocytes are attracted selectively by IFN-inducible protein-10; Tamaru M et al.; We have demonstrated that interferon-inducible protein-10 (IP-10) is produced in hepatocytes surrounded by infiltrative mononuclear cells in chronic hepatitis . To clarify the role of IP-10 in hepatitis, we examined the chemoattractive activity of IP-10 on liver-infiltrating lymphocytes in experimental animal models of hepatitis . IP-10 was specifically induced in the livers of mice treated intravenously (i.v.) with Con A, while monocyte chemotactic protein-1 (MCP-1) showed a much lower level of induction and neither RANTES nor macrophage inflammatory protein-1alpha (MIP-1alpha) was detected . The liver-infiltrating lymphocytes in Con A-induced hepatitis were attracted only by IP-10, and not by other chemokines such as RANTES, MCP-1 and MIP-1alpha . The chemoattractive effect of IP-10 was dose-dependent and was neutralized by monoclonal antibodies to IP-10 . The specific effect of IP-10 on liver-infiltrating lymphocytes was also seen on those obtained from rat livers with fulminant hepatitis induced by sequential treatment with killed Propionibacterium acnes (P . acnes) and LPS . Peripheral blood lymphocytes were slightly attracted by IP-10 as well as RANTES and MIP-1alpha, while hepatic resident lymphocytes were not . On the other hand, thioglycolate-elicited peritoneal macrophages did not respond to IP-10, although they did show a response to RANTES, MCP-1 and MIP-1alpha . These results indicated that IP-10 is a specific chemoattractant for T lymphocytes in the inflammatory liver tissues and may play a specific role in the development of hepatitis.

Appl Microbiol Biotechnol, 2000 Apr, 53(4), 435 - 40
Propionic acid fermentation of glycerol and glucose by Propionibacterium acidipropionici and Propionibacterium freudenreichii ssp . shermanii; Himmi EH et al.; A comparative study was carried out in anaerobic batch cultures on 20 g/l of either glycerol or glucose using two propionibacteria strains, Propionibacterium acidipropionici and Propionibacterium freudenreichii ssp . shermanii . In all cases, fermentation end-products were the same and consisted of propionic acid as the major product, acetic acid as the main by-product and two minor metabolites, n-propanol and succinic acid . Evidence was provided that greater production of propionic acid by propionibacteria was obtained with glycerol as carbon and energy sources . P . acidipropionici showed higher efficiency in glycerol conversion to propionic acid with a faster substrate consumption (0.64 g l(-1) h(-1)) and a higher propionic acid production (0.42 g l(-1) h(-1) and 0.79 mol/mol) . The almost exclusive production of propionic acid from glycerol by this bacterium suggested an homopropionic tendency of this fermentation . Acetic acid final concentration was two times lower on glycerol (2 g/l) than on glucose (4 g/l) for both micro-organisms . P . freudenreichii ssp . shermanii exhibited a glycerol fermentation pattern typical of non-associated glycerol-consumption-product formation . This could indicate a particular metabolism for P . freudenreichii ssp . shermanii oriented towards the production of other specific components . These results tend to show that glycerol could be an excellent alternative to conventional carbon sources such as carbohydrates for propionic acid production.

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