Orv Hetil, 2003 Jan 12, 144(2), 59 - 65 {Toxic shock syndrome caused by pyogenic bacteria}; Gabor Z et al.; Case reports and review of the literature . INTRODUCTION: Severe toxic shock syndrome caused by invasive infection with pyogenic bacteria Staphylococcus aureus or group A Streptococcus pyogenes, with high mortality rates in cases of the latter, remained one of the most problematic chapters of critical care medicine to date . AIMS: To give an overview on the epidemiology, clinical manifestations, the complex therapeutical approaches of the syndrome and, on the role and mechanisms of action of bacterial superantigens in the pathophysiological processes as well . METHODS AND RESULTS: Literary data, and some illustrative selected cases demonstrate that, the incidence of TSS shows increasing tendency worldwide and, that otherwise healthy, younger people are the most frequently affected . As for prognosis: early diagnosis and treatment with sufficient radicality are of decisive importance. Euro Surveill, 1998 Feb, 3(2), 11 - 14 Surveillance of systemic invasive disease caused by group A Streptococcus in Italy 1994-1996; Suligoi B et al.; In late May 1994, following reports of an outbreak of group A beta-haemolytic streptococcus (GAS) in the United Kingdom, the Istituto Superiore di Sanita (ISS) set up a surveillance system for systemic invasive GAS disease . The surveillance system was als Mayo Clin Proc, 2003 Mar, 78(3), 289 - 93 Validation and modification of streptococcal pharyngitis clinical prediction rules; McGinn TG et al.; OBJECTIVE: To validate a simplified version of the Walsh clinical prediction rules (CPRs) for the presence of streptococcal pharyngitis in an inner-city, ethnically diverse population . PATIENTS AND METHODS: This prospective study conducted in New York City, NY, from January 1,1997, to May 31,1997, consisted of 171 consecutive adult walk-in patients who presented with symptoms of upper respiratory tract infection and/or sore throat . The patients were assessed by using 5 clinical factors: cough, exposure to known streptococcal contact, temperature, tonsillar-pharyngeal exudates, and cervical lymphadenopathy . Throat cultures for group A beta-hemolytic streptococcus were obtained from all patients . Clinicians assessing the patients were unaware of throat culture results, and those processing the throat cultures were blinded to the clinical predictors . RESULTS: The prevalence of streptococcal pharyngitis was 24% (95% confidence interval, 18%-30%) . The simplified version of the Walsh CPR for streptococcal pharyngitis predicted accurately the probability of a positive culture in our diverse population (area under the receiver operating characteristic curve, 0.71) . The simplified CPR also showed clinically useful likelihood ratios and posterior probabilities . CONCLUSION: A simplified version of the Walsh CPR is accurate for diagnosing streptococcal pharyngitis in an inner-city population . This finding should provide clinicians more confidence in applying the CPR in similar clinical settings. Zh Mikrobiol Epidemiol Immunobiol, 2003 Jan-Feb, (1), 14 - 7 {Biliary microflora of patients with chronic pancreatitis}; Savitskaia KI et al.; Data on the contamination of bile specimens (1997 and 2001, 205 specimens, 137 cultures), examined in the Laboratory of Clinical Microbiology of the Vladimirsky Regional Research Clinical Institute, as well as data on the microflora composition in 40 specimens of bile, obtained from patients with clinically diagnosed chronic pancreatitis at the stage of exacerbation, are presented . Out of 40 specimens of bile 54 cultures of microorganisms were isolated; of these, 33.3% were bacteria of the genus Staphylococcus, Gram negative bacilli took the second place in occurrence (27.8%) and the third place belonged to bacteria of the genus Streptococcus (18.5%) . The antibiotic sensitivity of the isolated microorganisms is characterized. Curr Opin Drug Discov Devel, 2002 Sep, 5(5), 785 - 92 Novel approaches to antimicrobial therapy: peptide deformylase; Waller AS et al.; Peptide deformylase (PDF) represents one of the most exciting new targets for the development of novel antimicrobial chemotherapies . PDF is an essential bacterial metalloenzyme that deformylates the N-formylmethionine of newly synthesized bacterial polypeptides . Recent progress in understanding the structure and function of PDF has greatly facilitated the drug discovery process . In this article, the potential of PDF as an antimicrobial target is reviewed, and progress in the development of PDF inhibitors (PDFIs) is highlighted . Several structural classes of compounds have been reported as inhibitors of PDF . However, the real challenge has been in obtaining molecules with potent in vivo antibacterial activity against a range of drug-resistant pathogens . One of the more encouraging compounds reported, BB-83698 (British Biotech plc/Genesoft Inc), has shown in vivo efficacy against Streptococcus pneumoniae in both mouse thigh and lung infection models at doses equivalent to existing therapies . The published data suggest that PDFIs are a promising new class of antimicrobial agent best suited to treat respiratory tract infections (RTIs), but with the potential for activity against a variety of other pathogens . It is anticipated that the first PDFI targeting RTIs will enter the clinic soon. MCN Am J Matern Child Nurs, 2003 Mar-Apr, 28(2), 106 - 10 The relationship between abuse, sexually transmitted diseases, & group B streptococcus in childbearing women; Winn N et al.; PURPOSE: To examine the relationship between abuse, sexually transmitted diseases (STDs) and group B (GBS) infection among childbearing women using Selye's (1978) stress response theory . DESIGN AND METHODS: Retrospective chart review (n = 205) from two different clinical sites in Washington State, using the Childbearing Health Questionnaire to guide data collection . The women in the sample had an average age of 26.4 years and represented Anglo (81.4%), Hispanic (12%), Native American (3.9%), and African American (2.5%) ethnic groups . Thirty-eight percent ( = 78) reported experiencing physical and/or sexual abuse during their lifetimes and 31% had been diagnosed with an STD . RESULTS: Abuse was significantly related to STDs, and ethnicity emerged as a significant variable for the Hispanic women participating in this study . Findings indicated that infection with group B was also related to abuse status ( r=.60, p < or =.002) and to presence of herpes simplex virus-2 (r =.468, p<or =.01) . Total prevalence of STDs was positively related to abuse ( r=.78, p <or =.000) . Abused Hispanic women were more likely to be positive for STDs than were their nonabused counterparts ( p <or =.03) . CLINICAL IMPLICATIONS: The findings support previously published results that abuse is widespread in the United States and that abused women are at increased risk for STDs . These results highlight the need for regular screenings for abuse during healthcare, for abuse is a critical variable to consider when screening for STDs and GBS . STD screening typically occurs during the first prenatal visit and may need to be repeated for high-risk groups. Dent Mater, 2003 May, 19(3), 212 - 7 Zinc sulfate addition to glass-ionomer-based cements: influence on physical and antibacterial properties, zinc and fluoride release; Osinaga PW et al.; OBJECTIVES: The aim of this study is to evaluate the effect of ZnSO(4) addition to a conventional glass ionomer and a resin-modified glass ionomer on solubility, flexural strength, zinc and fluoride (F) release, and Streptococcus mutans growth inhibition . METHODS: 5 or 10% ZnSO(4) was added to Vitremer and Ketac-Fil powders . Solubility test was performed based on ISO 7489 . Flexural strength was determined by 3-point bending test based on ISO 4049 . Zn release/uptake was determined by atomic emission spectrometry; F release/uptake was measured using a F-specific electrode . Both release measurements were performed for 15 d before and 15 d after recharging . Antibacterial test was conducted according to agar plate methods against S . mutans, by measuring the inhibition halos in 1-h and 15-d specimens . Data were analyzed by ANOVA . RESULTS: Solubility increased with higher ZnSO(4) content, but remained below the ISO 7489 limit . Flexural strength was not affected by ZnSO(4) addition, and Vitremer performed better than Ketac-Fil . The control materials released no zinc . Vitremer with 10% ZnSO(4) released the highest amount of zinc . Fluoride release was similar for Ketac-Fil and Vitremer . In both cases, the highest amounts were released in the first 24 h . The growth inhibition halo of S . mutans was similar for both materials with highest content of ZnSO(4) and occurred only with 1-h specimens . SIGNIFICANCE: Zinc addition decreased microorganisms growth and improved fluoride release, without significantly affecting the materials' flexural strength and solubility. Fitoterapia, 2003 Feb, 74(1-2), 139 - 43 Evaluation of the anti-microbial and anti-inflammatory activities of the medicinal plants Dodonaea viscosa, Rumex nervosus and Rumex abyssinicus; Getie M et al.; The crude extracts of the leaves of Dodonaea viscosa and Rumex nervosus as well as of the root of Rumex abyssinicus were tested for anti-microbial and anti-inflammatory activities . It was observed that the three plants possess antibacterial activity against Streptococcus pyogenes and Staphylococcus aureus and strong activity against Coxsackie virus B3 and influenza A virus . In contrast, none of them exhibited anti-fungal activity . The anti-inflammatory activity test results verified that only R . abyssinicus inhibited the synthesis of prostaglandin (PG) E(2). Pharmacotherapy, 2003 Mar, 23(3), 349 - 59 Health care resource utilization associated with treatment of penicillin-susceptible and -nonsusceptible isolates of Streptococcus pneumoniae; Klepser ME et al.; Despite failure to correlate in vitro susceptibility with clinical outcomes for respiratory tract infections and bacteremia, resistance affects management of patients with pneumococcal infections . The economic impact of resistance among pneumococci has not been evaluated . We conducted a single-center, retrospective, observational, cohort study of hospitalized patients infected with Streptococcus pneumoniae isolated from blood or a respiratory source between January 1, 1995, and December 31, 1998 . Data were collected for 36 days surrounding the day that the first positive culture was collected . Patients were grouped according to isolate penicillin-susceptibility profile {susceptible minimum inhibitory concentration (MIC) < or = 0.06 microg/ml, nonsusceptible MIC > or = 0.125 microg/ml), and data were analyzed with respect to health care resource utilization patterns . Of 231 patients identified, 142 and 89 had susceptible and nonsusceptible isolates, respectively . Groups were similar with respect to demographics and comorbidities, except that patients infected with a nonsusceptible isolate were more likely to have the isolate obtained from a respiratory source and to have a history of recent antibiotic therapy . No difference was noted with respect to clinical outcome; however, patients infected with a nonsusceptible isolate had a longer median stay (14 vs 10 days, p<0.05) . They also had significantly higher total median costs (1600 dollars, 95% confidence interval 257-2943 dollars) due to room and nursing services . Infections caused by penicillin-nonsusceptible pneumococci were not associated with a worse outcome in hospitalized patients but were associated with increased cost of care. Pediatr Dent, 2003 Jan-Feb, 25(1), 43 - 8 Surface antibacterial properties of fissure sealants; Matalon S et al.; PURPOSE: Sealants form a physical barrier between the oral environment and deep fissures that contribute to caries prevention . It is postulated that sealants possessing antibacterial properties are advantageous . The purpose of this study was to evaluate the antibacterial properties of four pit and fissure sealants using direct contact test (DCT) and agar diffusion test (ADT) . METHODS: For the DCT, 8 samples of Helioseal F (Vivadent), Ultraseal XT (Ultadent-Weldent), Conseal F (SDI), and Dyract Seal (Dentsply) were placed on the sidewalls of wells of a 96-microtiter plate . After polymerization, freshly grown Streptococcus mutans cells (circa 1 x 10(6)) were placed on the surface of each sample for 1 hour at 37 degrees C . Fresh media was then added to each well and bacterial growth was followed for 16 hours by temperature-controlled spectrophotometer . Similarly prepared samples were aged in phosphate buffered saline for 14 and 30 days and the DCT was repeated . The ADT was performed by placing samples in uniform wells punched in agar plates . RESULTS: Freshly polymerized samples in the DCT, Dyract Seal and Ultraseal XT possessed prominent antibacterial properties . Dyract Seal also demonstrated the most potent antibacterial properties, which lasted 14 days but faded within 30 days . In ADT, the halo in the bacterial lawn was measured after 48 hours, and only Dyract Seal demonstrated an inhibition zone . CONCLUSIONS: The compomer-based sealant Dyract Seal possessed the most potent and longest lasting antibacterial activity. Lasers Med Sci, 2003, 18(1), 51 - 5 Bactericidal effects of different laser wavelengths on periodontopathic germs in photodynamic therapy; Chan Y et al.; This study was an attempt to clarify whether the bactericidal effects of photodynamic therapy (PDT) are wavelength or dose-dependent . We also attempted to create an optimised protocol for a light-based bactericidal modality to eliminate periodontal pathogens . Cultures of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphromonas gingivalis, Prevotella intermedia, and Streptococcus sanguis, were exposed to a He-Ne laser (632.8 nm) with a 30 mW power output, a 100 mW diode laser at 665 nm, or a 100 mW diode laser at 830 nm, in the presence or absence of methylene blue (MB) as a photosensitiser . A control group was also used with exposure to MB alone without laser exposure . The cultures were analysed by viable counts . The results indicated that exposure to the 100 mW laser light could eliminate up to 40% of bacteria on average . In particular, the most effective killing occurred with exposure to laser light in combination with the MB photosensitiser . The results of kinetic studies indicated that the best PDT response rate was achieved with a 60 s (energy density 21.2 J/cm(2)) exposure to the 665 nm wavelength diode laser in the presence photosensitiser . In this condition, approximately 95% of A . actinomycetemcomitans and F . nucleatum, and 99-100% of the black-pigmented bacteria ( P . gingivalis and P . intermedia) and S . sanguis were eliminated . These results showed that both wavelength and energy density are important factors, and that a low power laser of optimal wavelength and dosage, in combination with an appropriate photosensitiser, is a practical bactericidal modality . We concluded that using a diode laser of proper power and wavelength to deliver 60 s of irradiation could be a useful adjunct with mechanical debridement in the prevention of the re-colonisation of subgingival lesions by pathogenic microorganisms. Nat Med, 2003 Apr, 9(4), 424 - 30 Epub 2003 Mar 10. Geographic diversity and temporal trends of antimicrobial resistance in Streptococcus pneumoniae in the United States; McCormick AW et al.; Resistance of Streptococcus pneumoniae to antibiotics is increasing throughout the United States, with substantial variation among geographic regions . We show that patterns of geographic variation are best explained by the intensity of selection for resistance, which is reflected by differences between the proportions of resistance within individual serotypes, rather than by differences between the frequencies of particular serotypes . Using a mathematical transmission model, we analyzed temporal trends in the proportions of singly and dually resistant organisms and found that pneumococcal strains resistant to both penicillin and erythromycin are increasing faster than strains singly resistant to either . Using the model, we predict that by 1 July 2004, in the absence of a vaccine, 41% of pneumococci at the Centers for Disease Control and Prevention (CDC)'s Active Bacterial Core surveillance (ABCs) sites, taken together, will be dually resistant, with 5% resistant to penicillin only and 5% to erythromycin only. Clin Diagn Lab Immunol, 2003 Mar, 10(2), 246 - 51 Inhibition of pneumococcal adherence to human nasopharyngeal epithelial cells by anti-PsaA antibodies; Romero-Steiner S et al.; The role of pneumococcal (Pnc) surface adhesin A (PsaA) in the adherence of Streptococcus pneumoniae (pneumococcus) to host cells is not well defined . We examined the effect of anti-PsaA antibodies in an inhibition of adherence assay using Detroit 562 nasopharyngeal human epithelial cells . Rabbit polyclonal (Pab) anti-recombinant PsaA (rPsaA) sera, a purified mouse monoclonal antibody (MAb) (MAb 6F62G8E12), and 22 healthy adult sera with known anti-PsaA IgG levels (obtained by enzyme-linked immunosorbent assay) were evaluated for their abilities to inhibit Pnc adherence to confluent monolayers (measured as percent reduction in CFU counts compared to those of uninhibited controls) . Pnc adherence was dependent on capsular phenotype (no or low adherence for opaque strains) . With an inoculum of 10(4) to 10(5) bacteria/well, the mean +/- standard deviation count in controls was 163 +/- 32 CFU/well for transparent strains . Low adherence was observed for a PsaA-minus mutant even at higher inoculum doses . Mean percent inhibitions of adherence with Pab and MAb were 54 and 50%, respectively . Adult sera showed inhibition in a dose-response fashion with a range of 98 to 8%, depending on the serum anti-PsaA antibody concentration . Absorption of Pab with rPsaA restored Pnc adherence to control levels . Absorption of sera with a PsaA-minus mutant did not result in a significant decrease (P >0.05) of inhibition of adherence activity . Additionally, nearly 100% of Pnc adherence was inhibited by lipidated rPsaA at 2.5 micro g/ml . Our data support the argument that PsaA is an adhesin that mediates Pnc adherence to human nasopharyngeal cells . This functional assay may be useful in evaluating antibodies elicited in response to PsaA vaccination. Microbiology, 2003 Feb, 149(Pt 2), 497 - 504 Spontaneous sequence duplications within capsule genes cap8E and tts control phase variation in Streptococcus pneumoniae serotypes 8 and 37; Waite RD et al.; Capsule phase variants were isolated from serotype 8 and serotype 37 pneumococcal sorbarods . Sequence duplications within the essential capsule genes - cap8E (type 8) and tts (type 37) - were found to introduce frameshifts and generate acapsular phenotypes . Capsular revertants possessed wild-type cap8E and tts genes, indicating the precise excision of these duplications . Reversion frequencies (OFF-ON) fit a linear relationship between log(frequency of reversion) and log(length of duplication), previously found for serotype three pneumococci {Waite, R . D., Struthers, J . K . & Dowson, C . G . (2001) . Mol Microbiol 42, 1223-1232} . This study provides evidence that capsule phase variation can occur in pneumococcal serotypes with either simple (one to three genes) or complex capsule-encoding loci (12 genes) . Given the key role of CapE (the first monosaccharide transferase) in other clinically important pneumococci, such as serotypes 14 and 19F with complex capsular loci, the observed duplication within cap8E suggests that capsule phase variation could be controlled by tandem sequence duplication in capE homologues in other pneumococcal serotypes that construct their capsules through polymerization of lipid-linked intermediates. Microbiology, 2003 Feb, 149(Pt 2), 407 - 17 Role of the Streptococcus agalactiae ClpP serine protease in heat-induced stress defence and growth arrest; Nair S et al.; The main causes of microbial death after heat exposure are not well understood . Here, it is shown that the heat-shock protein ClpP plays a major role in heat-induced growth arrest in Streptococcus agalactiae . A mutant lacking the ClpP protease was more sensitive to the inhibitory effects of heat, salt and oxidative stress than the isogenic wild-type strain . During growth arrest, this mutant displayed important modifications of its total protein content, including a decreased level of essential metabolic enzymes such as the alcohol dehydrogenase . Analysis of protein carbonylation demonstrated that the ClpP protease plays a role in preventing accelerated protein oxidation . Higher levels of oxidized DnaK, a key modulator of the heat-shock regulon, were observed in the ClpP mutant and these were increased following heat shock . Accumulation of oxidized/inactivated DnaK might explain why the ClpP mutant was unable to properly synthesize DNA and proteins, and why it exhibited an aberrant cell morphology . Even though ClpP plays a minor role in the virulence of S . agalactiae in a murine infection model, the data presented here point to the importance of ClpP in oxidative stress defence in preventing heat-induced cell alterations. Microbiology, 2003 Feb, 149(Pt 2), 399 - 406 An amino acid change near the carboxyl terminus of the Streptococcus gordonii regulatory protein Rgg affects its abilities to bind DNA and influence expression of the glucosyltransferase gene gtfG; Vickerman MM et al.; The Streptococcus gordonii glucosyltransferase structural gene, gtfG, is located immediately downstream from its positive transcriptional regulatory determinant, rgg . Recent genetic studies have indicated that the 3' end of rgg is involved either directly as a binding site or indirectly, e.g . by playing a role in secondary structure, in the interaction of Rgg with the gtfG promoter . A previously identified spontaneous mutant with a point mutation near the 3' end of rgg had only approximately 25% of the parental level of glucosyltransferase activity . To determine if this decreased activity was due to a change in the DNA binding site of trans-acting Rgg, or due to a change in the Rgg protein itself, complementation analyses and DNA-binding studies were performed . In Rgg-deficient strains, the chromosomal rgg point mutation did not influence the ability of plasmid-borne rgg to increase glucosyltransferase expression . However, plasmids carrying parental rgg were able to increase glucosyltransferase activity and expression of a gtfG promoter fusion to a greater extent than plasmids carrying the mutant allele, indicating that the mutant Rgg protein had decreased activity . The ability of NH(2)-terminal (hexahistidine) tagged proteins to bind to a 107 bp dsDNA fragment corresponding to the region immediately upstream of gtfG was demonstrated by surface plasmon resonance . Despite their differences in activity, both mutant and parental recombinant Rgg proteins bound to this dsDNA, albeit with different strengths . These studies provide insights into functional domains of S . gordonii Rgg which influence glucosyltransferase expression, and may have implications for Rgg-like regulatory proteins in related bacteria. J Clin Microbiol, 2003 Mar, 41(3), 1307 - 10 emm Gene distribution among erythromycin-resistant and -susceptible Italian isolates of Streptococcus pyogenes; Zampaloni C et al.; The phenotypes and genetic determinants for macrolide resistance were determined for 167 erythromycin-resistant Streptococcus pyogenes strains . A cMLS phenotype was shown in 18% of the erythromycin-resistant strains, while inducible resistance was apparent in 31% and the M phenotype was apparent in 50% . The emm gene type of this set of resistant isolates and that of 48 erythromycin-sensitive isolates were determined . emm2 and emm48 were recorded only in the resistant strains of the M phenotype, while approximately all of the strains harboring the emm22 gene had the cMLS phenotype . More than 80% of the emm89-positive strains had the iMLS phenotype, and the same portion of emm4 strains presented the M phenotype . emm3 is recorded only among sensitive strains . The distribution of frequencies of the genetic determinant for the virulence factor M protein was significantly different both among organisms of different types of resistance and between resistant and sensitive populations of S . pyogenes under study. J Clin Microbiol, 2003 Mar, 41(3), 1004 - 9 Invasive Streptococcus iniae infections outside North America; Lau SK et al.; Streptococcus iniae, a fish pathogen causing infections in aquaculture farms worldwide, has only been reported to cause human infections in North America . In this article, we report the first two cases of invasive S . iniae infections in two Chinese patients outside North America . While the first patient presented with bacteremic cellulitis, which is the most common presentation in previous cases, the second patient represents the first recognized case of S . iniae osteomyelitis . Both S . iniae strains isolated from the two patients were either misidentified or unidentified by three commercial systems and were only identified by 16S rRNA gene sequencing . Since no currently available commercial system for bacterial identification includes S . iniae in its database, 16S rRNA gene sequencing is the most practical and reliable method to identify the bacterium at the moment . In contrast to the distinct genetic profile described previously in clinical isolates from Canada, the present two isolates and a clinical isolate from a Canadian patient were found to be genetically unrelated, as demonstrated by pulsed-field gel electrophoresis . Morphologically, colonies of both isolates were also larger, more beta-hemolytic and mucoid, which differ from the usual morphotype described for S . iniae . Owing to their habit of cooking and eating fresh fish, the Asian population is strongly associated with S . iniae infections . As a result of the difficulty in making microbiological diagnosis in patients with cellulitis and the problem of identification in most clinical microbiology laboratories, the prevalence of S . iniae infections, especially in the Asian population, may have been under-estimated. Ophthalmology, 2003 Mar, 110(3), 569 - 74 Bilateral cavernous sinus thromboses and intraorbital abscesses secondary to Streptococcus milleri; Watkins LM et al.; PURPOSE: To report the first case of bilateral cavernous sinus thromboses and bilateral intraorbital abscesses secondary to Streptococcus milleri . STUDY DESIGN: Single interventional case report . INTERVENTION AND TESTING: The findings of the ophthalmic evaluation, radiographic imaging, medical and surgical intervention, specimen cultures, and clinical course were analyzed . RESULTS: A 17-year-old female had bilateral proptosis, decreased vision in the left eye, and altered mental status at presentation . An orbital compartment syndrome developed in the left eye and purulent material was present after lateral canthotomy, suggestive of an intraorbital abscess . Magnetic resonance imaging (MRI) scans revealed bilateral cavernous sinus thromboses, and subsequent computed tomographic (CT) scans revealed bilateral intraorbital abscesses in the setting of acute ethmoid and sphenoid sinusitis . Antibiotic treatment and surgical drainage of the orbital abscess and sinuses was performed, and specimen cultures revealed S . milleri . After surgery, the patient experienced hearing loss and a right internal capsule infarct, in addition to complete vision loss in the left eye . A second intraorbital abscess developed in the right eye and was drained surgically . The vision remained 20/20 . CONCLUSIONS: Streptococcus milleri is a virulent organism with a propensity to form abscesses in multiple areas of the body and should be considered as a possible etiologic agent in abscess formation of the orbit and cavernous sinus thrombosis. Mol Microbiol, 2003 Mar, 47(6), 1589 - 99 Streptococcus dysgalactiae-derived mitogen (SDM), a novel bacterial superantigen: characterization of its biological activity and predicted tertiary structure; Miyoshi-Akiyama T et al.; A mitogenic substance, designated Streptococcus dysgalactiae-derived mitogen (SDM), was purified from S . dysgalactiae culture supernatant, and the gene encoding the mitogen was cloned . Both native and recombinant SDM expressed in Escherichia coli significantly activated human V beta 1+ and V beta 23+ T cells in association with major histocompatibility complex (MHC) class II molecules on accessory cells, indicating that SDM possesses superantigenic properties . The sdm gene consists of two segments encoding a signal peptide and a mature 25 kDa protein composed of 212 amino acids . Three of 34 S . dysgalactiae strains but none of 28 Streptococcus pyogenes strains examined carried sdm . Phylogenetic analysis indicated that SDM belongs to a family distinct from established bacterial superantigens . SDM showed around 30% homology with other superantigens at the amino acid sequence level . The tertiary structure of SDM was predicted by modelling onto streptococcal pyrogenic exotoxin C and streptococcal mitogenic exotoxin Z-2, both of which share highly homologous structure-determining regions . SDM showed overall structural similarity to both these superantigens . This is the first study to characterize fully a bacterial superantigen from S . dysgalactiae. Ned Tijdschr Geneeskd, 2003 Feb 8, 147(6), 225 - 9 {Three toddlers with a swelling in the neck}; Gerrits JA et al.; Three children, a girl aged 2.5 years and two boys aged 2 and 3 years respectively, presented with unilateral cervical lymphadenitis . The first patient had acute bacterial lymphadenitis due to group A Streptococcus, characterised by a painful cervical swelling of acute onset . The second patient had painless cervical lymphadenitis caused by Mycobacterium avium-intracellulare, which drained spontaneously . The third patient developed a non-tender, cervical swelling within a day . He too was systemically ill with fever and a headache . The lymphadenitis was caused by Bartonella henselae . After drainage, dissection and/or antibiotic therapy, all three recovered . A cervical mass in a young child is most frequently caused by an infectious lymphadenopathy . It rarely represents a malignant or other systemic disease . In many cases the diagnosis of infectious lymphadenitis can be made on the basis of the case history and clinical characteristics . However, when malignancy cannot be excluded tissue examination is always indicated. J Reprod Med, 2003 Feb, 48(2), 107 - 11 Limitations of the obstetric group B Streptococcus protocol; Nemunaitis-Keller J et al.; OBJECTIVE: To assess compliance with the Centers for Disease Control and Prevention (CDC) screening-based protocol for obstetric group B Streptococcus (GBS) and to determine an acceptable threshold for protocol failure . STUDY DESIGN: A retrospective chart review was carried out for all deliveries performed through the resident-run community clinic from January through June 1999 . Compliance with the CDC protocol was assessed by reviewing collected data from patient charts and comparing it to CDC requirements . Data were collected regarding patient demographics, antenatal GBS status, gestational age at screening, time of rupture of the membranes, time the antibiotic was given and time of delivery . RESULTS: A total of 248 charts were reviewed . Elective cesarean deliveries were excluded (25 charts) . Unknown culture status was found for 22 (9.9%) patients . Cultures were collected before 35 weeks' gestation in 39 (17.5%) patients and at > 37 weeks' gestation in 28 (12.6%) patients . Of those with known positive GBS status, 4 (7.0%) were not treated, and antibiotics were given less than four hours before delivery in 13 (24.5%) patients . Of those with unknown status, six (27.2%) were not treated . Overall, there was 70% compliance with the culture collection arm of the protocol and 87% compliance with the treatment arm . CONCLUSION: Fulfillment of CDC guidelines in this community setting is imperfect . There are several areas beyond physician control, including precipitous delivery and patient non-compliance . However, perhaps an acceptable threshold for limitations of adherence to the protocol can be reached. Jpn J Antibiot, 2002 Dec, 55(6), 697 - 729 {Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents . Special references to bacteria isolated between April 1999 and March 2000}; Mashita K et al.; The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in Japan since July 1982 . In this paper, the results obtained in the academic year 1999 (from April 1999 to March 2000) have been summarized . Two hundred seven cases were investigated, and 411 strains were isolated from 169 cases (81.6%) . Of those strains, 184 and 227 strains were from primary infections and postoperative infections, respectively . In primary infections, the isolation rates of anaerobes, Streptococcus spp., and Escherichia coli were higher than in postoperative infections, while in postoperative infections, those of Gram-positive aerobes were higher than in primary infections . Staphylococcus aureus were most frequently isolated among Gram-positive aerobes, Peptostreptococcus prevotii among Gram-positive anaerobes, E . coli among Gram-negative aerobes, and Bacteroides fragilis among Gram-negative anaerobes . In primary infections, the percentage of Gram-negative aerobes, which gradually increased by the year 1998, decreased in the year 1999 . The percentage of Gram-negative anaerobes increased, while that of Gram-negative bacteria was equivalent to that in the last year . In postoperative infections, the percentage of Gram-negative anaerobes, which continuously increased after the year 1990, decreased, while that of Gram-positive aerobes, which decreased in the last year, increased . Methicillin-resistant S . aureus accounted for 70.7% of S . aureus (41 strains) . Either the number of strain or the percentage of MRSA decreased . The susceptibilities of E . coli and Klebsiella pneumoniae decreased against third and forth generation cephems, oxacephems, and monobactams . The susceptibilities of P . aeruginosa to carbapenems tend to decrease after the year 1997 . S . aureus showed good susceptibilities to the tested drugs including arbekacin, vancomycin, and teicoplanin. Rapid Commun Mass Spectrom, 2003, 17(6), 576 - 82 Identification of hyaluronic acid oligosaccharides by direct coupling of capillary electrophoresis with electrospray ion trap mass spectrometry; Kuhn AV et al.; A new method for the identification of oligosaccharides obtained by enzymatic digestion of hyaluronic acid (HA) with bacterial hyaluronidase (HA lyase, E.C . 4.2.2.1, from Streptococcus agalactiae) using online capillary electrophoresis/electrospray mass spectrometry (CE/ESI-MS) is presented . A fused-silica capillary coated with polyacrylamide was used with a 40 mM ammonium acetate buffer at pH 9.0 and a separation voltage of +30 kV applied to the inlet . Separation was achieved for oligosaccharides containing 4-16 monomers . The migration behavior follows the chain length of the oligomers, regardless of charge state . However, no linear relationship was found for the relation between mobility and chain length . Using an ion trap mass analyzer, complementary structural information was obtained by MS/MS and MS(n) experiments . J Med Microbiol, 2003 Mar, 52(Pt 3), 251 - 8 Antimicrobial susceptibility patterns and genomic diversity in strains of Streptococcus pyogenes isolated in 1978-1997 in different Brazilian cities; de Melo MC et al.; Penicillin has been the antimicrobial of choice for the treatment of Streptococcus pyogenes infections for almost six decades . Although penicillin-resistant isolates have not been described to date, clinical failures have been reported after treatment with beta-lactams . In this study, we analysed the antimicrobial susceptibility and genetic diversity of S . pyogenes isolates obtained from healthy carriers or patients in different cities in the south and south east of Brazil . The MICs were determined for penicillin and seven other antimicrobials . Penicillin tolerance was also investigated . Genetic diversity was analysed by PFGE after SmaI fragmentation of the genomic DNA . All 211 isolates tested were susceptible to penicillin (MIC 0.0025-0.02 mg l(-1)) . Four isolates were moderately penicillin-tolerant (MBC/MIC = 16 mg l(-1)) . Most of the other drugs tested were very active against the strains examined, except for tetracycline, to which 50 % of strains were resistant . We also found extensive genetic diversity, in that 60 different patterns were recognized in the 96 strains studied . Indeed, we found no correlation between tetracycline resistance and clonality . Despite this diversity, some PFGE patterns persisted for up to 18 years and specific clone types were spread over different geographical locations J Biol Chem, 2003 May 9, 278(19), 17336 - 43 Epub 2003 Mar 05. Maturation processing and characterization of streptopain; Chen CY et al.; Streptopain is a cysteine protease expressed by Streptococcus pyogenes . To study the maturation mechanism of streptopain, wild-type and Q186N, C192S, H340R, N356D and W357A mutant proteins were expressed in Escherichia coli and purified to homogeneity . Proteolytic analyses showed that the maturation of prostreptococcal pyrogenic exotoxin B zymogen (pro-SPE B) involves eight intermediates with a combination of cis- and trans-processing . Based on the sequences of these intermediates, the substrate specificity of streptopain favors a hydrophobic residue at the P2 site . The relative autocatalytic rates of these mutants exhibited the order Q186N > W357A > N356D, C192S, H340R . Interestingly, the N356D mutant containing protease activity could not be converted into the 28-kDa form by autoprocessing . This observation suggested that Asn(356) might involve the cis-processing of the propeptide . In addition, the maturation rates of pro-SPE B with trypsin and plasmin were 10- and 60-fold slower than that with active mature streptopain . These findings indicate that active mature streptopain likely plays the most important role in the maturation of pro-SPE B under physiological conditions. J Biol Chem, 2003 May 9, 278(19), 16561 - 6 Epub 2003 Mar 05. SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides; Frick IM et al.; Some isolates of the significant human pathogen Streptococcus pyogenes, including virulent strains of the M1 serotype, secrete protein SIC . This molecule, secreted in large quantities, interferes with complement function . As a result of natural selection, SIC shows a high degree of variation . Here we provide a plausible explanation for this variation and the fact that strains of the M1 serotype are the most frequent cause of severe invasive S . pyogenes infections . Thus, protein SIC was found to inactivate human neutrophil alpha-defensin and LL-37, two major antibacterial peptides involved in bacterial clearance . This inactivation protected S . pyogenes against the antibacterial effect of the peptides . Moreover, SIC isolated from S . pyogenes of the M1 serotype was more powerful in this respect than SIC variants from strains of M serotypes 12 and 55, serotypes rarely connected with invasive infections. FEMS Microbiol Lett, 2003 Feb 28, 219(2), 209 - 14 Development of PCR assays for detection of Streptococcus canis; Hassan AA et al.; Streptococcus canis isolates, also including S . canis of artificially contaminated milk, could be identified by polymerase chain reaction (PCR) amplification using oligonucleotide primers designed according to species-specific parts of the 16S rRNA gene and, after sequencing, according to S . canis-specific parts of the 16S-23S rDNA intergenic spacer region and with oligonucleotide primers detecting an internal fragment of the group G streptococcal CAMP factor gene cfg . The 16S rRNA gene- and CAMP factor gene cfg-specific oligonucleotide primers could be used together in a multiplex PCR . No cross-reactivities could be observed with other group G streptococcal isolates or with any of the other control strains of various streptococcal species and serogroups . The PCR methods presented in this study allowed a rapid and reliable identification of S . canis and might help to improve the diagnosis of this bacterial species in animal and human infections. FEMS Microbiol Lett, 2003 Feb 28, 219(2), 195 - 201 Allelic variation in srtAs of Streptococcus suis strains; Osaki M et al.; Streptococcus suis NCTC10234 possesses five srtA homologs: srtA encodes sortase, which anchors surface proteins with an LPXTG motif to the cell wall, while the functions of the other four homologs (the srtBCD cluster and srtE) remain unknown . The genetic organization of the srtA region was found to be conserved in the 59 S . suis strains examined in this study . Although the srtAs in three of these strains showed strong sequence divergence, their functions were verified to be overlapping by genetic complementation, indicating the functional conservation of srtAs during the evolution of these strains . These results indicate the importance of an srtA-mediated cell wall sorting system for displaying proteins on the surface of S . suis. Microb Pathog, 2003 Jan, 34(1), 27 - 37 Role of suilysin in pathogenesis of Streptococcus suis capsular serotype 2; Lun S et al.; Three suilysin (SLY) knockout mutant strains of Streptococcus suis serotype 2 were generated by allelic replacement from one North American and two European wild type strains . The mutants were characterized by Southern blot, Western blot and phenotyping . In vitro bactericidal testing showed that both wild type and SLY mutants were resistant to bactericidal factors in whole pig blood . To demonstrate the role of SLY during S . suis infection, four animal trials were carried out using young pigs . Either high dose (4 x 10(6)CFU/ml/pig) or low dose (0.5 x 10(6)CFU/ml/pig) live cell aerosol was applied to the pharynx . In one trial, a low challenge dose of North American strain SX332 and its isogenic sly(-) mutant strain (SX932) resulted in acute disease in 3/5 of pigs exposed to the wild type strain, while 5/5 of pigs exposed to the mutant strain survived the trial . In the repeat trial, 1/8 of pigs in wild type group and 6/8 of pigs in mutant group developed disease . The high dose trial with 332/932 pair showed that 4/8 pigs challenged with wild type and 5/8 of pigs challenged with mutant strain developed disease respectively . The third low dose trial, using European strain 31533 and its isogenic sly(-) mutant strain SX911, showed that 1/8 of pigs challenged with the wild type strain and 4/8 of pigs challenged with the corresponding mutant strain developed disease . All the diseased pigs showed fever, clinical signs and developed septicemia . S . suis was isolated from tissue samples such as brain, submandibular lymph node, lung, spleen, liver, heart or joint . Serum antibody titer against cell surface proteins changed little while the antibody titer against SLY increased only in the wild type group after challenge . sly gene was cloned and expressed in E . coli . The recombinant SLY (rSLY) protein showed 800 hemolysin units per microg protein . In vitro study showed that rSLY triggered TNFalpha production by human monocytes and IL-6 production by pig pulmonary alveolar macrophages and monocytes . Thus, the results of this study suggest that SLY does not seem to be a critical virulence factor for S . suis serotype 2 respiratory infection, but by stimulating cytokine release it may play a role in innate immunity. J Med Chem, 2003 Mar 13, 46(6), 1005 - 15 Synthesis and structure-activity relationships of 5-amino-6-fluoro-1-{(1R,2S)-2-fluorocyclopropan-1-yl}-8-methylquinolonecarboxylic acid antibacterials having fluorinated 7-{(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl} substituents; Inagaki H et al.; A series of novel 5-amino-6-fluoro-1-{(1R,2S)-2-fluorocyclopropan-1-yl}-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE) . These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX) . Among them, the 7-{(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyrrolidin-1-yl} derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens. J Bacteriol, 2003 Mar, 185(6), 2051 - 8 Characterization of a novel fucose-regulated promoter (PfcsK) suitable for gene essentiality and antibacterial mode-of-action studies in Streptococcus pneumoniae; Chan PF et al.; The promoter of the Streptococcus pneumoniae putative fuculose kinase gene (fcsK), the first gene of a novel fucose utilization operon, is induced by fucose and repressed by glucose or sucrose . When the streptococcal polypeptide deformylase (PDF) gene (def1, encoding PDF) was placed under the control of P(fcsK), fucose-dependent growth of the S . pneumoniae (P(fcsK)::def1) strain was observed, confirming the essential nature of PDF in this organism . The mode of antibacterial action of actinonin, a known PDF inhibitor, was also confirmed with this strain . The endogenous fuculose kinase promoter is a tightly regulated, titratable promoter which will be useful for target validation and for confirmation of the mode of action of novel antibacterial drugs in S . pneumoniae. J Bacteriol, 2003 Mar, 185(6), 1857 - 69 Novel genomic rearrangement that affects expression of the Streptococcus pyogenes streptolysin O (slo) gene; Savic DJ et al.; A RecA-independent chromosomal rearrangement in the upstream region of the streptolysin O (slo) gene of Streptococcus pyogenes which affects slo expression was identified . PCR analysis was used to demonstrate that this kind of rearrangement was found in several strains of different lineages . Chromosomal loci involved in the recombination were found to be 746 kb apart on the 1.85-Mb-long chromosome . The primary structure of the splicing region, the reproducibility of the rearrangement, and the fact that reconstructed recombinant molecules fused to erm and lacZ reporter genes affected their expression indicate that this event is not accidental but may play a role in the expression of the slo gene . In addition, the product of the recombining DNAs, including the splicing site, does not follow any example of a known recombination mechanism . The implications of this rearrangement for slo expression are discussed. J Antimicrob Chemother, 2003 Mar, 51(3), 715 - 9 Spain14-5 international multiresistant Streptococcus pneumoniae clone resistant to fluoroquinolones and other families of antibiotics; Perez-Trallero E et al.; The Spain(14)-5 international multiresistant clone was initially described as resistant to penicillin, tetracycline, chloramphenicol and trimethoprim/sulfamethoxazole . In Gipuzkoa, Spain, Streptococcus pneumoniae isolated from 16 patients, and determined by PFGE and multilocus sequence typing to belong to the Spain(14)-5 clone, showed further resistance to fluoroquinolones (all strains had point mutations in the parC and gyrA genes) . In addition, most strains showed resistance to amoxicillin (MIC > or = 8 mg/L), cefotaxime (MIC > or = 2 mg/L), macrolides and lincosamides . Two strains were resistant to rifampicin (MIC 8 mg/L) . The multiresistance observed in these isolates converts the Spain(14)-5 clone into one of the most, if not the most, multiresistant of the international clones described. J Antimicrob Chemother, 2003 Mar, 51(3), 707 - 10 A multidrug efflux phenotype mutant of Streptococcus pyogenes; Jones HE et al.; We describe a mutant of Streptococcus pyogenes NCTC 8198 with a multidrug efflux phenotype . A mutant selected with ethidium bromide showed a four-fold rise in MIC of norfloxacin, a 16-fold rise in MIC of ethidium bromide and an eight-fold rise in MIC of acriflavine when compared with the parent strain . The MICs were unaffected by the efflux pump inhibitors reserpine, rescinnamine and verapamil . The mutant's ethidium bromide MIC was reduced two-fold by norfloxacin . Ethidium bromide accumulation after 10 min was 58% lower in the mutant compared with the parent . This difference was not affected by carbonyl cyanide m-chlorophenylhydrazone. J Antimicrob Chemother, 2003 Mar, 51(3), 691 - 6 Breakthrough pneumococcal bacteraemia in patients treated with clarithromycin or oral beta-lactams; Van Kerkhoven D et al.; The incidence of penicillin- and erythromycin-resistant strains of Streptococcus pneumoniae has increased considerably in Belgium . The medical charts of all patients with pneumococcal bacteraemia who were admitted to hospital over a period of 3 years (n = 136) were reviewed to identify treatment failure of outpatient antibiotic therapy . Twelve patients had received antibiotics for at least 48 h prior to admission . Four treatment failures received clarithromycin as pre-hospitalization therapy, and S . pneumoniae from all four patients were highly resistant to macrolides . Five patients failed on co-amoxiclav, whereas their S . pneumoniae were susceptible to penicillin and amoxicillin.This observation suggests that macrolide resistance is clinically relevant and leads to treatment failure, whereas suboptimal dosing may explain breakthrough pneumococcal bacteraemia in beta-lactam-treated patients. J Antimicrob Chemother, 2003 Mar, 51(3), 639 - 49 Activity of daptomycin against susceptible and multidrug-resistant Gram-positive pathogens collected in the SECURE study (Europe) during 2000-2001; Critchley IA et al.; Antibiotic resistance was prevalent in Gram-positive pathogens collected from 40 sites in 15 European countries during 2000-2001 . Among Staphylococcus aureus, 27.3% of all isolates submitted were resistant to oxacillin and ranged from 0% of isolates from the Netherlands to 36.9% of isolates from Portugal . The overall prevalence of vancomycin-resistant Enterococcus faecium was 25.1%, with Italy submitting the largest percentage of resistant isolates (60.6%) . For Streptococcus pneumoniae, 9.4% of all isolates collected were resistant to penicillin with variation by country from 0% in the Netherlands to 20.7% in Portugal . Multidrug resistance (MDR), defined as concurrent resistance to three or more antimicrobials of different chemical classes, was observed in 24.6% of S . aureus, 19.6% of E . faecium and 3.6% of S . pneumoniae . The directed spectrum agents daptomycin, linezolid and quinupristin-dalfopristin were active in vitro against all isolates regardless of their resistance to other agents . Daptomycin and quinupristin-dalfopristin (MIC(90)s 0.5 mg/L) were equally active against oxacillin-resistant S . aureus compared with linezolid (MIC(90) 2 mg/L) . The activities of daptomycin, quinupristin-dalfopristin and linezolid were not affected by resistance to vancomycin in E . faecium (MIC(90)s of 4, 2 and 2 mg/L, respectively) . Daptomycin was more active against penicillin-resistant S . pneumoniae (MIC(90) 0.25 mg/L) than was quinupristin-dalfopristin (MIC(90) 0.5 mg/L) or linezolid (MIC(90) 2 mg/L) . Daptomycin was highly active against clinically important Gram-positive pathogens, including those that were multiply resistant to currently available agents . The results of this study provide a benchmark of the activity of daptomycin against contemporary European isolates and will serve as a baseline to monitor future changes in the susceptibility of these organisms to daptomycin. Curr Opin Microbiol, 2003 Feb, 6(1), 50 - 5 IdeS and SpeB: immunoglobulin-degrading cysteine proteinases of Streptococcus pyogenes; von Pawel-Rammingen U et al.; The Gram-positive bacterium Streptococcus pyogenes is a major human pathogen causing substantial morbidity and mortality in society . S . pyogenes has evolved numerous molecular mechanisms to avoid the various actions of the human immune system and has established means to modulate both adaptive and innate immune responses . S . pyogenes produces and secretes proteolytic enzymes, which have an important impact on the ability of the bacteria to survive in the human host . Prominent among these are two immunoglobulin-degrading enzymes: the newly discovered streptococcal cysteine proteinase, IdeS, and the classical cysteine proteinase of S . pyogenes, SpeB. Obstet Gynecol Surv, 2003 Mar, 58(3), 191 - 6 Group B streptococcus: prevention of early-onset neonatal sepsis; Platt JS et al.; Group B streptococcus (GBS) was recognized as a major pathogen of neonatal disease in the 1970s . With a case-fatality rate of 5% to 20%, prevention of GBS neonatal disease has been an ongoing concern . The Centers for Disease Control and Prevention (CDC), and American College of Obstetricians and Gynecologists (ACOG) published guidelines for preventive strategies in 1996 . These strategies, either a risk-based or a culture-based program, have been responsible for reduced incidence of GBS-newborn disease from 1.7 to 0.4 per 1,000 live births in the years 1993 to 1999 . However, there has been considerable variability in practice patterns . Reanalysis now shows that a culture-based prevention strategy provides greater reduction in early-onset neonatal disease than a risk-based protocol . The CDC replacement guidelines of August 2002 recommend culture-based GBS prevention; the risk-based strategy is no longer supported . Continued efforts to eradicate GBS-newborn disease require an understanding of the pathogen, colonization, and transmission, GBS sampling and detection methods, and maternal therapy . Until a reliable vaccination against GBS is developed, prevention of neonatal GBS disease will rely upon intrapartum treatment of maternal carriers . TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to define the pathogen, describe the methods of transmission and detection, and outline the current recommendations for maternal group B streptococcus therapy. Pediatr Res, 2003 Apr, 53(4), 566 - 72 Epub 2003 Feb 20. Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response; Dorschner RA et al.; The expression of antimicrobial peptides and proteins is an important innate immune defense mechanism that has recently been shown to be essential for cutaneous defense against invasive bacterial disease . Newborns have an immature cellular immune defense system that leads to increased susceptibility to infections . Here we show that skin from embryonic and newborn mice, as well as human newborn foreskin, express antimicrobial peptides of the cathelicidin and beta-defensin gene families . Immunohistochemistry and in situ hybridization demonstrated abundant cathelicidin protein and mRNA is present in normal skin during the perinatal period . Quantitative real-time PCR showed mouse cathelicidin expression (CRAMP) is 10- to 100-fold greater in the perinatal period than adult . Murine beta-defensins-1 and -4 and human beta-defensin-2 were also present in newborn skin . Combined, human cathelicidin (LL-37/hCAP/18) and beta-defensin-2 demonstrated synergistic antimicrobial activity and efficiently killed group B Streptococcus, an important neonatal pathogen . Antimicrobial peptides may therefore provide a compensatory innate defense mechanism during development of cellular immune response mechanisms in the newborn period. Arch Microbiol, 2003 Mar, 179(3), 205 - 13 Epub 2003 Feb 04. Molecular characterization of HPr and related enzymes, and regulation of HPr phosphorylation in the ruminal bacterium Streptococcus bovis; Asanuma N et al.; Molecular properties of HPr, enzyme I, and HPr kinase in Streptococcus bovis, and the regulation of HPr phosphorylation were examined . The genes encoding HPr (ptsH) and enzyme I (ptsI) were found to be cotranscribed . Two transcriptional start sites were detected in a region upstream of the HPr kinase gene (hprK) . HPr kinase had both HPr-phosphorylating and HPr-dephosphorylating activities . The importance of phosphorylation of Ser-46 in HPr was shown by using a mutant HPr in which Ser-46 was replaced by Ala . When S . bovis was grown in glucose-limited medium, the amount of seryl-phosphorylated HPr (HPr-{Ser-P}) decreased drastically as the growth rate decreased . In contrast, the amount of histidyl-phosphorylated HPr (HPr-{His-P}) increased gradually as the growth rate decreased . The amount of HPr kinase did not greatly change with the growth phase, whereas the intracellular P(i) concentration increased as the growth rate decreased . HPr-{Ser-P} decreased as the intracellular P(i) increased as a consequence of inhibition of HPr kinase activity by P(i) and simultaneous enhancement of HPr-{Ser-P} phosphatase activity by P(i) . Thus, it is conceivable that the ratio of HPr-{Ser-P} to HPr-{His-P} is regulated by the bifunctional activity of HPr kinase in response to intracellular P(i) concentration. ANZ J Surg, 2003 Mar, 73(3), 136 - 9 Acute septic arthritis of the hip in children in northern Australia; Gandini D; BACKGROUND: The epidemiology, microbiology and clinical management of all children under 15 years of age presenting with acute septic arthritis of the hip to Royal Darwin Hospital from July 1994 to December 1999 were reviewed and the diagnostic value of various biological markers assessed . METHODS: Systematic review was undertaken of case notes of patients identified by searching the computerized hospital patient database and the admission records for the children's ward . RESULTS: Eleven cases were identified: 10 aboriginal and one caucasian . The mean temperature, white cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) at presentation were 39.2 degrees C, 15,500/mL, 65 mm/h and 144 mg/L, respectively . All had ESR and/or CRP >20 . Plain radiographs and ultrasonography were abnormal in 1/8 and 5/6 cases, respectively . Pathogens were isolated in nine cases: Staphylococcus aureus (n = 6), Streptococcus pyogenes (n = 2) and Streptococcus pneumoniae (n = 1) . Patients received intravenous antibiotics for 8.6 days (range: 3-15 days) and subsequent oral antibiotics for 22 days (range: 0-42 days) . The mean (range) time from hospital admission to arthrotomy; from hospital admission to antibiotic administration; and the overall hospital stay was 23 h (range: 3-48 h); 6 h (range: 0-48 h); and 41 days (range: 6-110 days), respectively . CONCLUSIONS: Elevation of temperature, white cell count, ESR and CRP were useful indicators of septic arthritis but initial diagnosis must be made on a clinical basis . Many patients had to be transferred from regional aboriginal communities and there was significant delay from onset of symptoms to arthrotomy. J Periodontal Res, 2003 Apr, 38(2), 130 - 4 Effects of safrole on the defensive functions of human neutrophils; Hung SL et al.; The effects of safrole on the defensive functions of human neutrophils were examined . At the concentrations employed in this study, safrole did not significantly affect the viability of peripheral blood neutrophils as verified by their ability to exclude trypan blue dye . However, exposure of neutrophils to safrole inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose dependent manner . In addition, safrole inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction . In conclusion, the results demonstrated that safrole reduced the antibacterial activity and the superoxide anion production of neutrophils . Inhibition of the defensive functions of neutrophils may be one possible mechanism by which safrole compromises the oral health. Acta Paediatr Taiwan, 2002 Sep-Oct, 43(5), 291 - 4 Necrotizing pneumonia caused by Streptococcus pneumoniae in a child with systemic lupus erythematosus; Chiu WJ et al.; Necrotizing pneumonia caused by Streptococcus pneumoniae is not an uncommon disease in children . Here we report a case of necrotizing pneumonia caused by Streptococcus pneumoniae in a 13-year-old girl . She was a case of systemic lupus erythematosus (SLE), and has long been treated with corticosteroids and azathioprine . She acquired pneumococcal necrotizing pneumonia later on . After appropriate antimicrobial therapy and surgical intervention, her condition stabilized and she recovered gradually . The present case suggests the need for a comprehensive diagnostic approach in patients with SLE who are undergoing immunosuppressive therapy, in order to screen for the possibility of infections if a new pulmonary pathologic process is present, even if the patient has no symptoms/signs indicating severe pulmonary infections. Hua Xi Kou Qiang Yi Xue Za Zhi, 2002 Oct, 20(5), 374 - 6 {A study on screening effective immunization route of anticaries DNA vaccine pcDNA3-gtfB}; Yang J et al.; OBJECTIVE: Glucosyltransferase-B (GTF-B) of Streptococcus mutans has been implicated as a principal virulent factor in the development of dental caries . The objective was to use recombined plasmid pcDNA-gtfB expressing multiple antigen of glucosyltransferase-B as gene vaccine to immunize rats through different route, and to investigate the immunization effects of immunization routes . METHODS: A total of 18 Wistar rats were divided into 3 groups, including the quadriceps injection group, the intransal irrigation group and the submandibular gland-targeted injection group . The serum IgG and salivary IgA were assayed by using ELISA after pcDNA3-gtfB immunization . The serum IgG and salivary IgA in different groups were compared using statistical one-way ANOVA . RESULTS: Compared these 3 groups, the serum IgG in the quadriceps injection group was much higher than those of other two groups (P < 0.01), while the salivary IgA of the submandibular gland-targeted injection was much higher than those of other two groups (P < 0.01) . CONCLUSION: It is indicated pcDNA3-gtfB is good candidate for anticarious gene vaccine, and submandibular gland-targeted injection is an effective immunization route for stimulating salivary IgA. Kansenshogaku Zasshi, 2002 Dec, 76(12), 1003 - 9 {The utility of the Pneumonia PORT prediction rule for evaluating the severity of community-acquired pneumonia in Japan . The relationship between disease severity and drug-resistant Streptococcus pneumoniae}; Nishiyama O et al.; To examine the utility of the Pneumonia PORT prediction rule for evaluating the severity of community-acquired pneumonia (CAP) in Japan, 127 consecutive patients with CAP admitted during one-year period were recruited and stratified by the rule . The relationship between CAP severity determined by the rule and drug-resistant Streptococcus pneumoniae was also investigated . The number of the patients classified into each class was 20 (15.7%) in class I, 32 (25.2%) in class II, 32 (25.2%) in class III, 31 (24.4%) in class IV, and 12 (9.4%) in class V, respectively . Risk class-specific mortality rate was 0% in class I and II, 3.1% in class III, 3.2% in class IV, and 41.7% in class V, respectively . Twenty-seven patients (21.3%) were diagnosed as pneumococcal pneumonia . In terms of penicillin-susceptibility of Streptococcus pneumoniae, 19 strains (70.4%) were penicillin-susceptible Streptococcus pneumoniae (PSSP) . Five (18.5%) were penicillin-intermediate Streptococcus pneumoniae (PISP), and 3 (11.1%) were penicillin-resistant Streptococcus pneumoniae (PRSP) . Highly resistant pneumococci with penicillin MIC > or = 4.0 micrograms/mL was not observed . For severity of drug-resistant pneumococcal pneumonia, 3 patients infected with PISP were classified as class IV, 2 with PISP were as class V, 2 with PRSP were as class IV, and 1 with PRSP was as class V . The patients with drug-resistant pneumococcal pneumonia were classified as high risk classes (class IV to V), however, the mortality rate was low (0%) . In conclusion, the Pneumonia PORT prediction rule is effective for evaluating the severity of CAP in Japan, especially in classifying the class V patients who are related to high mortality . The mortality rate of the patients with drug-resistant pneumococcal pneumonia was low. Med Hypotheses, 2003 Feb, 60(2), 171 - 4 The next step in infectious disease: taming bacteria; Jones AH; Except for immunization programs our warfare with bacteria has always been a frontal assault with antibiotics . In this warfare we win battles, but with every new battle the enemy gets stronger . We need other options . Recent experience suggests two alternatives . First, public health measures designed to control the spread of infectious disease are associated with the selection of less virulent strains of microorganisms . Second, the same selection pressures obtained by public health measures outside the body are brought into play when we inhibit the adherence of bacteria within the body . Two recent studies using food sugars known to inhibit bacterial adherence show long-term benefits best explained by the previously observed decreases in bacterial virulence, following chronic exposure to the respective substances . Cranberry juice selects for less uropathogenic strains of Escherichia coli and xylitol for less caries producing Streptococcus mutans . The ability of these substances to reduce bacterial adherence in the human host has been known for some time, but poorly utilized . Their in vitro ability to decrease virulence has been reported but not clinically studied. Expert Opin Investig Drugs, 2003 Mar, 12(3), 379 - 99 Novel antibacterial agents for the treatment of serious Gram-positive infections; Abbanat D et al.; With the continuing development of clinical drug resistance among bacteria and the advent of resistance to the recently released agents quinupristin-dalfopristin and linezolid, the need for new, effective agents to treat multi-drug-resistant Gram-positive infections remains important . This review focuses on agents presently in clinical development for the treatment of serious multidrug-resistant staphylococcal, enterococcal and pneumococcal infections, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and penicillin-resistant Streptococcus pneumoniae . Agents to be discussed that affect the prokaryotic cell wall include the antimethicillin-resistant S . aureus cephalosporins BAL9141 and RWJ-54428, the glycopeptides oritavancin and dalbavancin and the lipopeptide daptomycin . Topoisomerase inhibitors include the fluoroquinolones gemifloxacin, sitafloxacin and garenoxacin . Protein synthesis inhibitors are represented by the ketolides telithromycin and cethromycin, the oxazolidinones and the glycylcycline tigecycline . Although each of these compounds has demonstrated antibacterial activity against antibiotic-resistant pathogens, their final regulatory approval will depend on an acceptable clinical safety profile. Lasers Surg Med, 2003, 32(3), 189 - 96 Efficacy of NaOCl/H2O2 irrigation and GaAlAs laser in decontamination of root canals in vitro; Kreisler M et al.; BACKGROUND AND OBJECTIVES: To investigate the bactericidal effect of an 809 nm semiconductor laser alone, and in combination with NaOCl/H(2)O(2) irrigation in root canals in vitro . STUDY DESIGN/MATERIALS AND METHODS: A total of 72 human single-rooted teeth extracted for periodontal reasons were included . The crowns were removed, the roots shortened to a length of 12 mm, and the canals enlarged up to an apical size of #50 file . The specimens were autoclaved and incubated with a suspension of Streptococcus sanguinis (ATCC 10556) . Laser irradiation was performed on a PC-controlled XY translation stage . A 200 micron optic fiber was used . Twelve specimens were irradiated at a power output of 1.5, 3.0, and 4.5 W in the cw-mode . The total irradiation time was 60 seconds per canal . Twelve specimens were rinsed with NaOCl and H(2)O(2) only, 12 were rinsed and laser treated, and 12 served as untreated controls . After laser treatment, the specimens were sonicated and the bacterial growth was examined by counting colony forming units on blood agar plates . Temperature changes at the outer root surface during irradiation were registered by means of thermocouples . Treated and control specimens were investigated by means of scanning electron microscopy . RESULTS: Mean bacterial reductions of 0.35 log steps at a power output of 1.5 W, 1.44 at 3.0 W, and 2.84 at 4.5 W were calculated . Bacterial reduction by the NaOCl/H(2)O(2) solution alone was 1.48 and comparable to that achieved by irradiation at 3.0 W . With a log kill 2.85, the combination of rinsing and laser irradiation at 3.0 W resulted in a further significant bacterial reduction as compared to rinsing alone (P = 0.004) . Irradiation did not result in excessive heat generation at the root surface . Carbonization of the root canal wall was observed in single teeth at 3.0 and 4.5 W and no controlled sealing of the dentinal tubules could be achieved in the root canal . CONCLUSIONS: The application of the diode laser might be an adjunct to conventional endodontic treatment when used in combination with a NaOCl/H(2)O(2) solution . Circ J, 2003 Mar, 67(3), 275 - 6 Complete heart block resulting from quadricuspid aortic valve penicillin-resistant pneumococcal endocarditis: a case report; Watanabe Y et al.; A 62-year-old woman was referred to hospital to be treated for complete heart block with syncope . A quadricuspid aortic valve without vegetation and aortic valve regurgitation (AR) were observed by transesophageal echocardiography . Blood culture showed penicillin-resistant Streptococcus pneumoniae . The patient received a permanent pacemaker implantation (VDD type) and was given antibiotics . Although infection improved, heart failure was not improved because AR hemodynamic changes became worse . An aortic valve replacement was performed using a prosthesis on the 26th day of hospitalization . The patient recovered and was discharged. Antimicrob Agents Chemother, 2003 Mar, 47(3), 1151 - 3 Lack of synergy of erythromycin combined with penicillin or cefotaxime against Streptococcus pneumoniae in vitro; Lin E et al.; We investigated a possible synergistic effect of a macrolide and beta-lactams against Streptococcus pneumoniae strains with different resistance profiles . Checkerboard and time-kill assays of erythromycin combined with penicillin or cefotaxime essentially showed indifference, suggesting that these antibiotics in combinations in vitro act substantially as individuals in their activity against S . pneumoniae. Antimicrob Agents Chemother, 2003 Mar, 47(3), 1112 - 4 Erythromycin and clindamycin resistance and telithromycin susceptibility in Streptococcus agalactiae; Betriu C et al.; The rates of resistance to erythromycin and clindamycin among Streptococcus agalactiae strains isolated in our hospital increased from 4.2 and 0.8% in 1993 to 17.4 and 12.1%, respectively, in 2001 . Erythromycin resistance was mainly due to the presence of an Erm(B) methylase, while the M phenotype was detected in 3.8% of the strains . Telithromycin was very active against erythromycin-resistant strains, irrespective of their mechanisms of macrolide resistance. Antimicrob Agents Chemother, 2003 Mar, 47(3), 1096 - 100 Mechanism of fluoroquinolone resistance is an important factor in determining the antimicrobial effect of gemifloxacin against Streptococcus pneumoniae in an in vitro pharmacokinetic model; MacGowan AP et al.; Antibacterial effect and emergence of resistance to gemifloxacin and levofloxacin were studied in an in vitro pharmacokinetic model of infection . A panel of Streptococcus pneumoniae strains with known mechanisms of resistance were used; two strains had no known resistance mechanism, two had efflux pumps, three had gyrA plus parC mutations, and one had only a parC mutation . Gemifloxacin MICs were in the range of 0.016 to 0.25 mg/liter, and levofloxacin MICs ranged from 1 to 16 mg/liter . Antimicrobial effect was measured by area under the bacterial-kill curve up to 72 h, and emergence of resistance was determined by population analysis profile before and during drug exposure . The area under the curve (AUC)/MIC ratios for gemifloxacin and levofloxacin were 35 to 544 and 3 to 48, respectively . As expected on the basis of these AUC/MIC ratio differences, antibacterial effect was much greater for gemifloxacin than levofloxacin . In the gemifloxacin simulations, mechanism of resistance as well as MIC determined the antibacterial effect, as indicated by gemifloxacin's greater effect against efflux strains compared to those with gyrA or parC mutations despite similar MICs . This was not true of levofloxacin . Emergence of resistance was not easily demonstrated with either agent, and mechanism of resistance did not have any impact on it. Antimicrob Agents Chemother, 2003 Mar, 47(3), 1088 - 95 Activities of moxifloxacin against, and emergence of resistance in, Streptococcus pneumoniae and Pseudomonas aeruginosa in an in vitro pharmacokinetic model; MacGowan AP et al.; The pharmacodynamics of moxifloxacin against Streptococcus pneumoniae and Pseudomonas aeruginosa were investigated in a pharmacokinetic infection model . Three strains of S . pneumoniae, moxifloxacin, and two strains of P . aeruginosa were used . Antibacterial effect and emergence of resistance were measured for both species over a 72-h period using an initial inoculum of about 10(8) CFU/ml . At equivalent area under the curve (AUC)/MIC ratios, S . pneumoniae was cleared from the model while P . aeruginosa was not . For S . pneumoniae, the area under the bacterial kill curve up to 72 h could be related to AUC/MIC ratio using an inhibitory maximum effect (E(max)) model (concentration required for 50% E(max) {EC(50)}, 45 +/- 22; r(2), 0.97) . For P . aeruginosa even at the highest AUC/MIC ratio (427), bacterial clearance was insufficient for the EC(50) to be calculated . Emergence of resistance occurred with P . aeruginosa but not to any significant extent with S . pneumoniae . Emergence of resistance in P . aeruginosa as measured by population analysis profile (PAP-AUC) was dependent on drug exposure and time of exposure . In weighted least-squares regression analysis AUC/MIC ratio was predictive of PAP-AUC . When emergence of resistance was measured by the time for the colony counts on media containing antibiotic to increase by 2 logs, again AUC/MIC was the best predictor of emergence of resistance . However, for both experiments using S . pneumoniae and P . aeruginosa the correlation between all the pharmacodynamic parameters was high . These data indicate that for a given fluoroquinolone the magnitude of the AUC/MIC ratio for antibacterial effect is dependent on the bacterial species . Emergence of resistance is dependent on (i) species, (ii) duration of drug exposure, and (iii) drug exposure . A single AUC/MIC ratio magnitude is not adequate to predict antibacterial effect or emergence of resistance for all bacterial species. Antimicrob Agents Chemother, 2003 Mar, 47(3), 923 - 31 In vitro activity of S-3578, a new broad-spectrum cephalosporin active against methicillin-resistant staphylococci; Fujimura T et al.; The in vitro antibacterial activity of S-3578, a new parenteral cephalosporin, against clinical isolates was evaluated . The MICs of the drug at which 90% of the isolates were inhibited were 4 micro g/ml for methicillin-resistant Staphylococcus aureus (MRSA) and 2 micro g/ml for methicillin-resistant Staphylococcus epidermidis, which were fourfold higher than and equal to those of vancomycin, respectively . The anti-MRSA activity of S-3578 was considered to be due to its high affinity for penicillin-binding protein 2a (50% inhibitory concentration, 4.5 micro g/ml) . In time-kill studies with 10 strains each of MRSA and methicillin-susceptible S . aureus, S-3578 caused more than a 4-log(10) decrease of viable cells on the average at twice the MIC after 24 h of exposure, indicating that it had potent bactericidal activity . Furthermore, in population analysis of MRSA strains with heterogeneous or homogeneous resistance to imipenem, no colonies emerged from about 10(9) cells on agar plates containing twice the MIC of S-3578, suggesting the low frequency of emergence of S-3578-resistant strains from MRSA . S-3578 was also highly active against penicillin-resistant Streptococcus pneumoniae (PRSP), with a MIC(90) of 1 micro g/ml, which was comparable to that of ceftriaxone . S-3578 also had antibacterial activity against a variety of gram-negative bacteria including Pseudomonas aeruginosa, though its activity was not superior to that of cefepime . In conclusion, S-3578 exhibited a broad antibacterial spectrum and, particularly, had excellent activity against gram-positive bacteria including methicillin-resistant staphylococci and PRSP . Thus, S-3578 was considered to be worthy of further evaluation. Antimicrob Agents Chemother, 2003 Mar, 47(3), 863 - 8 Low-level resistance to rifampin in Streptococcus pneumoniae; Meier PS et al.; Rifampin is recommended for combination therapy of meningitis due to beta-lactam-resistant Streptococcus pneumoniae . High-level rifampin resistance (MIC, > or =4 mg/liter) has been mapped to point mutations in clusters I and III of rpoB of the pneumococcus . The molecular basis of low-level resistance (MICs, > or =0.5 and <4 mg/liter) was analyzed . Spontaneous mutants of clinical pneumococcal isolates were selected on Columbia sheep blood agar plates containing rifampin at 0.5, 4, 10, or 50 mg/liter . Low-level resistance could be assigned to mutations in cluster II (I(545)N, I(545)L) . Sensitive (MIC, <0.048 mg/liter) wild-type strains acquired low-level resistance at a rate approximately 10 times higher than that at which they acquired high-level resistance (average mutation frequencies, 2.4 x 10(-7) for low-level resistance versus 2.9 x 10(-8) for high-level resistance {P < 0.0001}) . In second-step experiments, the frequencies of mutations from low- to high-level resistance were over 10 times higher than the frequencies of mutations from susceptibility to high-level resistance (average mutation frequencies, 7.2 x 10(-7) versus 5.0 x 10(-8) {P < 0.001}) . Mutants with low-level resistance were stable upon passage . Sequencing of a clinical isolate with low-level resistance (MIC, 0.5 mg/liter) revealed a Q(150)R mutation upstream of cluster I . The frequencies of mutations to high-level resistance for this strain were even higher than the rates observed for the in vitro mutants . Therefore, a resistance-mediating mutation located outside clusters I, II, and III has been described for the first time in the pneumococcus . In vitro low-level rifampin resistance in S . pneumoniae could be mapped to cluster II of rpoB . Mutants of pneumococcus with low-level resistance may be selected in vivo during therapy in tissue compartments with low antibiotic concentrations and play a role in the development of resistance. Emerg Infect Dis, 2003 Feb, 9(2), 211 - 6 Using hospital antibiogram data to assess regional pneumococcal resistance to antibiotics; Stein CR et al.; Antimicrobial resistance to penicillin and macrolides in Streptococcus pneumoniae has increased in the United States over the past decade . Considerable geographic variation in susceptibility necessitates regional resistance tracking . Traditional active surveillance is labor intensive and costly . We collected antibiogram reports from North Carolina hospitals and assessed pneumococcal susceptibility to multiple agents from 1996 through 2000 . Susceptibility in North Carolina was consistently lower than the national average . Aggregating antibiogram data is a feasible and timely method of monitoring regional susceptibility patterns and may also prove beneficial in measuring the effects of interventions to decrease antimicrobial resistance. Ethiop Med J, 2002 Jul, 40(3), 241 - 9 Investigation on the antibacterial properties of garlic (Allium sativum) on pneumonia causing bacteria; Dikasso D et al.; The antibacterial activity of the crude aqueous extract of garlic was investigated against some pneumonia causing bacteria by an agar dilution technique . The results revealed that Streptococcus pneumoniae standard test organism was completely inhibited by 7.8 mg/ml of media and the clinical isolate of Klebsiella pneumoniae was completely inhibited by 24.38 mg/ml of media, indicating that Streptococcus pneumoniae is the most sensitive and Klebsiella pneumoniae the least . Garlic could be used as an effective antibacterial agent for these pathogenic microorganisms. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2002 Aug, 31(6), 464 - 466 {Influence of different DNA extractions on the identification of streptococcus sanguis group by arbitrary primed polymerase chain reaction}; Zhang WD et al.; OBJECTIVE: To assess the influence of different DNA extractions on the identification of streptococcus sanguis group (SSG) species by arbitrary primed polymerase chain reaction (AP-PCR) . METHODS: AP-PCR was used to distinguish SSG species by designing 25bp arbitrary primer 5'AAG AGA GGA GCT AGC TCT TCT TGG A 3', and the genomic DNA was extracted by 3 methods . RESULTS: There were great differences in the main band of DNA polymorphism among SSG species . The similar band could be got from the different DNA extractions in the same species . CONCLUSION: Different DNA extractions have no influence on the identification of SSG. Immunol Lett, 2003 Mar 3, 86(1), 85 - 91 Naturally occurring immune response against bacteria commonly involved in upper respiratory tract infections: analysis of the antigen-specific salivary IgA levels; Rossi GA et al.; Lyophilized bacterial lysates, which actively stimulate the immune response, are widely used as vaccines or 'biological response modifiers' in subjects with recurrent bacterial respiratory infections . Since vaccines are indicated in the absence or in the presence of a weak constitutive immune response activity, a better knowledge on the 'naturally' occurring antibacterial immune response at the oropharingeal level should be helpful . A study was, therefore, designed to quantify the presence of salivary IgA directed against surface antigens bacteria frequently involved in the pathogenesis of upper respiratory tract infections: Klebsiella pneumoniae (KP), Staphylococcus aureus (SA), Streptococcus pyogenes (SPy), Morraxella catarrhalis (MC), Haemophylus influenzae (HI), and Streptococcus pnumoniae (SPn) . In 34 volunteers (21 adults and 13 children), salivary fluid was collected and the presence of microorganism-specific IgA antibodies evaluated by a novel enzyme immuno-assay . In the whole population only 29 and 24% of subjects had IgA directed, respectively, to KP and SA, while the immune-response against other microbes was detectable in a small population ranging from 12 to 15% of all subjects studied . We found higher proportions of individuals with strain specific salivary IgA in the adult than in the pediatric population for all the microorganism evaluated . In addition, in children, the only strain inducing a significant production of specific IgA at oropharingeal level was KP . Interestingly, only ten out of 21 adults and two out 13 children have at least one significantly high antibody titer against one of the bacteria evaluated . Nevertheless, when a group of healthy donors was treated with a polyvalent mechanical bacterial lysate (Ismigen t.), the large majority developed a specific immune-response in the salivary fluid . These results are thus consistent with the good features of the novel enzyme-immunoassay and with a poor frequency of naturally induced specific anti-microbe antibodies in children and in adults despite the presence on recurrent respiratory infections in their clinical history. Nippon Geka Gakkai Zasshi, 2002 Dec, 103(12), 851 - 5 {Prosthetic valve endocarditis: complication following cardiac surgery}; Motomura N et al.; Prosthetic valve endocarditis (PVE) is a rare but serious complication following valve replacement surgery . Early-phase PVE, which occurs within 60 days of valve replacement, may be associated with nosocomial or intraoperative infection . The primary organism of this type is the Staphylococcus group . Late-phase PVE, which usually occurs more than one year after valve replacement, may be caused by a mechanism similar to that of native valve endocarditis . The primary causative organism of this type would thus be similar to that of native valve endocarditis, which is the Streptococcus group . To treat PVE effectively, it is extremely important to identify the primary causative organism . If uncontrollable cardiac failure or infection occurs, a second valve replacement is absolutely indicated . A cryopreserved aortic valve allograft, if available, is the first choice for PVE . Features such as cell viability, less compliance mismatch, and postantibiotic process could be reasons for the anti-infective characteristics of cryopreserved allografts . Currently, allograft valves are not widely available in Japan; therefore, conventional prosthetic valves are usually used . The use of antibiotic-soaked prosthetic valves or stentless xenograft valves has also been attempted . A genetic or tissue engineering approach could open a new era to overcome this lethal complication. Hua Xi Yi Ke Da Xue Xue Bao, 2002 Jan, 33(1), 62 - 4, 107 {The influence of two implant materials on the growth of three subgingival predominant bacteria}; Gao N et al.; OBJECTIVE: Commercially pure titanium and titanium alloy as dental implants have show impressive clinical results . Despite the high success rates, some implants do fail . Compared to those studies on osseointegration of implants, the information pertaining to their failure is little . Further studies on the relationship between implant material and micro-organism are needed . The purpose of this investigation is to study the effect of two commonly used implant materials Titanium (TA2) and Ti-6AI-4V alloy (TC4) on the growth behaviour of three subgingival predominant bacteria Streptococcus sanguis (S . s), Porphyromanus gingivalis (P . g), Fusobacterium nucleatum (F . n) and their mixture . METHODS: Under anaerobic condition, bacterial suspensions of S.s, P.g, F.n and their mixture were incubated together with the two implant materials respectively, setting the same bacterial suspensions as controls . After 2, 7 and 14 days, the bacterial growth amount was assayed by means of clone forming unit (CFU) method . The pH value of the bacterial suspension was determined by pH-Meter . RESULTS: The results showed that there was no difference in amount of bacterial growth or pH value between TA2 group and TC4 group (P > 0.05) . There was also no statistically significant change as to the proportion of individual bacteria in bacterial mixture or the pH value of culture suspension . CONCLUSION: Under the condition of this investigation, the two studies implant materials have no examined influences on the growth of the subgingival bacteria and the pH value of their culture environment. Rev Neurol, 2003 Feb, 36 Suppl 1, S95 - 107 {Autoimmune neuropsychiatric disorders associated to infection by streptococcus in the paediatric age: PANDAS}; Betancourt YM et al.; INTRODUCTION: The acronym PANDAS (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) describes the neuropsychiatric disorders resulting from an autoimmune response to an infection by streptococcus in children . AIMS: The aim of this study was to clinically analyse 38 patients under the age of 16 with tics, Tourette syndrome (TS) or obsessive compulsive disorder (OCD) and their possible association to an infection caused by group A beta-haemolytic streptococcus (GABHS) . METHOD: We reviewed the medical records at the Instituto Neurologico in Valencia (Venezuela) over a 12 year period (1988-2000) . All the patients met the inclusion criteria set out by the National Institute of Mental Health in Bethesda (1997) and the DSM-IV . RESULTS: Onset of the symptoms was higher in the group of schoolchildren (n=24), followed by the group of preschool children (n=8) and adolescents (n=6) . Males were predominant (n=33) (86.8%) . 17 patients presented chronic tics (44.7%), 13 had transitory tics (34.2%) and there were eight cases of TS (21.1%) . The most frequently related comorbid disorders were: difficulties in learning (n=30) (78.9%), ADHD (n=27) (71.1%), OCD 14 (36.8%), sleep disorders (n=14) (36.8%), behavioural disorders (n=12) (31.6%), language disorders (n=11) (28.9%), psychomotor disorders (n=10) (26.3%) and nocturnal enuresis (n=7) (18.4%) . Electroencephalogram patterns were abnormal in 72.4% (n=12), and the disorganised pattern was the most frequently observed (n=12) (41.4%), followed by a slow diffuse pattern (n= 7) (24.1%) and the left centro-parieto-temporal focal paroxysmal specific pattern (n=7) (24.1%) . Less frequently we found unspecific generalised paroxysmal patterns, in four cases (13.8%), and asymmetrical patterns (n=1) (3.4%) . The association with an infection by streptococcus was shown in two cases, which amounted to 5.2% of the sample . CONCLUSIONS: The obtained are similar to those reported in the literature . Only 5.2% of the cases were linked to a prior streptococcus infection. J Infect Dis, 2003 Feb 15, 187(4), 604 - 12 Epub 2003 Jan 28. Intrahost sequence variation in the streptococcal inhibitor of complement gene in patients with human pharyngitis; Matsumoto M et al.; Selection of new variants of the streptococcal inhibitor of complement protein has been implicated in the perpetuation of epidemics caused by serotype M1 strains of group A Streptococcus (GAS) . The frequency at which new streptococcal inhibitor of complement (Sic) variants arise in an infected individual is not known . To study this issue, the sic gene was sequenced in 100 isolates cultured from throat swabs of each of 20 patients with acute pharyngitis caused by serotype M1 GAS . Five patients were infected with GAS populations expressing 2 Sic variants characterized by deletion of a region of the protein . In contrast, no intrahost variation was detected in the number of a pentanucleotide repeat (CAAAA) that controls production of a bacterial cell-surface collagen-like protein by slipped-strand mispairing . Sic variation occurs at a sufficient frequency in vivo to result in mixed infections on the mucosal surface of human hosts, potentially contributing to pathogen survival. J Infect Dis, 2003 Feb 15, 187(4), 597 - 603 Epub 2003 Feb 07. Survival of Streptococcus pyogenes within host phagocytic cells: a pathogenic mechanism for persistence and systemic invasion; Medina E et al.; Streptococcus pyogenes is generally an extracellular pathogen that can survive and persist within the host by circumventing the host defense mechanisms . To achieve this, S . pyogenes has developed a number of strategies to circumvent the host immune system (e.g., virulence factors directed to prevent phagocytosis) . By use of a murine model of skin infection, it was shown that survival within host phagocytic cells constitutes an additional strategy used by S . pyogenes to evade the host defenses and disseminate . Viable microorganisms were isolated from mouse phagocytic cells after in vitro or during in vivo infection . The capacity of intracellularly located bacteria to establish infection was demonstrated by the efficiency of gentamicin-treated neutrophils isolated from infected mice to transfer infection when injected intravenously into naive mice . The ability of S . pyogenes to exploit the inflammatory response of the host by surviving inside phagocytic cells may constitute an additional virulence mechanism of this pathogen. J Infect Dis, 2003 Feb 15, 187(4), 589 - 96 Epub 2003 Jan 29. Nationwide surveillance of nasopharyngeal Streptococcus pneumoniae isolates from children with respiratory infection, Switzerland, 1998-1999; Muhlemann K et al.; The surveillance of pneumococcal antibiotic resistance and serotype distribution is hampered by the relatively low numbers of invasive pneumococcal infections . In Switzerland, a nationwide sentinel surveillance network was used to assess antibiotic resistance and serotype distribution among 1179 pneumococcal isolates cultured from 2769 nasopharyngeal swabs obtained from outpatients with acute otitis media or pneumonia during 1998 and 1999 . The proportion of penicillin-susceptible pneumococcal isolates overall (87%) and among infants <2 years old (81%) was comparable to that of invasive isolates (90% and 81%, respectively) . The high number of nasopharyngeal isolates allowed for the detection of a rapid increase in the number of penicillin-nonsusceptible pneumococcal (PNSP) strains in the West region of Switzerland, partly because of an epidemic caused by the 19F clone of Streptococcus pneumoniae . Clustering of risk factors for the carriage of PNSP isolates further explained the geographic variation in resistance rates . The nationwide sentinel surveillance of nasopharyngeal pneumococcus proved to be valuable for the monitoring of antibiotic resistance, risk factors for carriage of PNSP isolates, and serotype distribution and for the detection of the emergence of a new epidemic clone. J Dermatol, 2003 Jan, 30(1), 69 - 71 A case of baboon syndrome associated with group a streptococcal infection; Ichimiya M et al.; We described a 21-year-old Japanese patient with sore throat, fever, and diffuse erythema on the neck, trunk, and limbs . Erythema markedly appeared on the neck, axillary, antecubital, and popliteal fossae . However, other skin signs of scarlet fever such as red strawberry tongue and linear petechial eruption did not appear . Before his visit to our clinic, he had been diagnosed as pharyngitis and treated with cefaclor 750 mg daily for six days . However, the symptoms did not improve . Oral prednisolone of 20 mg daily rapidly improved all the symptoms . Pharyngeal culture grew Streptococcus pyogenes that was sensitive to cefaclor . Laboratory findings showed elevated serum levels of antibody against streptolysin O . Together with the distribution of erythema, culture of Streptococcal pyogenes, and elevated anti-streptolysin O titer, the diagnosis of baboon syndrome associated with streptococcal infection was made . This seems to be the first report of baboon syndrome due to streptococcal infection. Arch Dis Child, 2003 Mar, 88(3), 211 - 4 Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy; Lakshman R et al.; AIMS: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years . METHODS: Non-randomised, unblinded controlled study of 2-5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls . Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls) . The swabs were cultured and serotyped for Streptococcus pneumoniae . RESULTS: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups . CONCLUSIONS: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2-5 years of age. Am J Respir Crit Care Med, 2003 Mar 1, 167(5), 764 - 70 Impaired pulmonary inflammatory responses are a prominent feature of streptococcal pneumonia in mice with experimental emphysema; Inoue S et al.; Little is known about why patients with chronic obstructive pulmonary disease are susceptible to bacterial infections . Using an animal model of pulmonary emphysema, we investigated the inflammatory responses to bacterial infection . After intratracheal infection with Streptococcus pneumoniae (10(3)-10(7) cfu/mouse), the control mice did not die . However, the mice with emphysema died in a dose-dependent manner . Bronchoalveolar lavage fluid, examined 24 hours after infection showed that the numbers of total cells and neutrophils, in addition to murine tumor necrosis factor-alpha and macrophage inflammatory protein-2 concentrations, were significantly less in the mice with emphysema compared with the control mice . Histopathologic findings revealed that the alveoli were filled with inflammatory cells and exudate in the control mice but not in the mice with emphysema . Seventy-two hours after infection, serum cytokine levels were significantly higher in the mice with emphysema, and significant numbers of S . pneumoniae were detected in both the whole lung tissues and the blood of mice with emphysema . These findings suggest that the inflammatory response in mice with emphysema was impaired at the site of bacterial infection despite the bacteremia, which accelerated severe systemic inflammatory responses . Accordingly, intra-alveolar but not systemic immune responses to bacterial infection were impaired in the presence of experimental emphysema. Protein Expr Purif, 2003 Feb, 27(2), 346 - 56 Cloning, over-expression, purification, and characterisation of N-acetylneuraminate synthase from Streptococcus agalactiae; Suryanti V et al.; N-acetylneuraminate synthase (NeuAc-synthase; E.C . 4.1.3.19) is one of the two enzymes responsible for sialic acid (N-acetylneuraminic acid) synthesis in bacteria . Potential genes encoding NeuAc synthase in Streptococcus agalactiae and Bacillus subtilis were identified from a BLAST search of the EMBL/GenBank/DDBJ database using the E . coli neuB gene sequence as a probe and the genes cloned and expressed at high level in Escherichia coli . The neuB gene of S . agalactiae was shown to encode an active NeuAc synthase, whereas the spsE gene product from B . subtilis did not have this activity . Expression of the native S . agalactiae neuB gene product enzyme in E . coli resulted in a product that was prone to proteolysis during purification so the protein was tagged with a hexa-histidine tag at its N-terminus and the enzyme was rapidly purified to homogeneity by ammonium sulphate fractionation and Ni-chelating affinity chromatography in two steps . Measurement of the subunit molecular mass by electrospray ionisation mass spectrometry (M(r) = 38, 987 +/- 3) and of the native molecular mass by gel filtration chromatography (M(r) = 78,000) clearly demonstrated that the enzyme is dimeric . The effects of EDTA, temperature, and pH on the activity of the S . agalactiae NeuAc synthase were examined . Enzyme activity was maximal at pH 7 and was dependent on the presence of metal ions such as Mg(2+), Mn(2+) or Co(2+) . The purified enzyme was inhibited by the reagent phenylglyoxal and the substrates N-acetyl mannosamine or phosphoenol pyruvate afforded protection against this inhibition, suggesting that one or more arginine residues are involved in substrate recognition and binding . The ease of expression and the properties of the enzyme should now permit a thorough study of the specificity of the enzyme and provide the prerequisites for attempts to alter this specificity by directed evolution for the production of novel sialic acid analogues . Ann Otol Rhinol Laryngol, 2003 Feb, 112(2), 191 - 4 Natural history of sigmoid sinus thrombosis; Agarwal A et al.; To demonstrate the evolution of sigmoid sinus thrombosis, we performed a prospective observational study on a 6-year-old girl who presented with mastoiditis, epidural abscess, and occipital osteomyelitis from multiple drug-resistant Streptococcus pneumoniae . She underwent mastoidectomy and partial occipital craniectomy . This procedure produced a window in the occipital bone that allowed serial ultrasonography of the sigmoid sinus during medical treatment . Computed tomography was performed, followed by weekly Doppler ultrasonography used to monitor resolution of sigmoid sinus thrombosis . The natural history of a treated episode of sigmoid sinus thrombosis was illustrated . Venous occlusion resolved over a 4- to 6-week period without surgical drainage or venous anticoagulants . Collateral flow, reversal of normal venous flow, and ultimate return to normal venous transport characterized the period of resolution . We conclude that an occluded sigmoid sinus from mastoiditis can naturally recanalize . Aberrant venous flow can be demonstrated during the period of resolution . This case supports a conservative approach to management of the occluded sinus and suggests that 4 to 6 weeks of antibiotic therapy after removal of perisinus infection is sufficient for cure. Infect Immun, 2003 Mar, 71(3), 1462 - 9 Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases; Batten MR et al.; The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated . Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1 . The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors . However, the substitutions had a substantial effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease . This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement for either proline or threonine at residues 227 to 228 . By contrast, the IgA1 proteases of Streptococcus oralis, Streptococcus sanguis, and Streptococcus mitis had an absolute requirement for proline at 227 but not for threonine at 228, which could be replaced by valine . There was evidence in S . mitis that proteases from different strains may have different amino acid requirements for cleavage . Remarkably, some streptococcal proteases appeared able to cleave the hinge at a distant alternative site if substitution prevented efficient cleavage of the original site . Hence, this study has identified key residues required for the recognition of the IgA1 hinge as a substrate by streptococcal IgA1 proteases, and it marks a preliminary step towards development of specific enzyme inhibitors. Infect Immun, 2003 Mar, 71(3), 1179 - 84 Immunogenicity and protective immunity induced by synthetic peptides associated with putative immunodominant regions of Streptococcus mutans glucan-binding protein B; Smith DJ et al.; Glucan-binding protein B (GbpB) from Streptococcus mutans has been shown to induce protective immunity to dental caries in experimental models . Having recently sequenced the gbpB gene, our objective in this study was to identify immunogenic regions within the GbpB sequence for use in subunit vaccines . Potential regions of immunogenicity were sought by use of a matrix-based algorithm (EpiMatrix) to estimate the binding characteristics of peptides derived from the GbpB sequence by using a database of known major histocompatibility complex class II binding alleles . Screening the entire sequence revealed several peptides with estimated high binding probabilities . Two N-terminal 20-mer peptides (SYI and QGQ) subtending two of these regions were synthesized . A preliminary experiment, in which these peptides were synthesized in the multiple antigenic peptide format and were used to subcutaneously immunize Sprague-Dawley rats twice at a 21-day interval, revealed that the SYI peptide induced a higher percentage of responses to the inciting peptide as well as to intact GbpB, as measured by enzyme-linked immunosorbent assay . The effect of immunization with the SYI peptide construct on the cariogenicity of S . mutans was then investigated by immunizing weanling Sprague-Dawley rats twice at a 9-day interval with SYI or with phosphate-buffered saline . All rats were then orally infected with S . mutans strain SJ . After a 78-day infection period, the SYI-immunized groups had significant reductions in dental caries on both smooth and occlusal surfaces compared with the sham-immunized group . Thus, these experiments indicated that at least one linear sequence, derived from the N-terminal third of GbpB, was sufficiently immunogenic to induce a protective immune response in this experimental rat model for dental caries. Infect Immun, 2003 Mar, 71(3), 1042 - 55 Identification and characterization of a Streptococcus pyogenes operon involved in binding of hemoproteins and acquisition of iron; Bates CS et al.; The hemolytic Streptococcus pyogenes can use a variety of heme compounds as an iron source . In this study, we investigate hemoprotein utilization by S . pyogenes . We demonstrate that surface proteins contribute to the binding of hemoproteins to S . pyogenes . We identify an ABC transporter from the iron complex family named sia for streptococcal iron acquisition, which consists of a lipoprotein (siaA), membrane permease (siaB), and ATPase (siaC) . The sia transporter is part of a highly conserved, iron regulated, 10-gene operon . SiaA, which was localized to the cell membrane, could specifically bind hemoglobin . The operon's first gene encodes a novel bacterial protein that bound hemoglobin, myoglobin, heme-albumin, and hemoglobin-haptoglobin (but not apo-haptoglobin) and therefore was named Shr, for streptococcal hemoprotein receptor . PhoZ fusion and Western blot analysis showed that Shr has a leader peptide and is found in both membrane-bound and soluble forms . An M1 SF370 strain with a polar mutation in shr was more resistant to streptonigrin and hydrogen peroxide, suggesting decreased iron uptake . The addition of hemoglobin to the culture medium increased cell resistance to hydrogen peroxide in SF370 but not in the mutant, implying the sia operon may be involved in hemoglobin-dependent resistance to oxidative stress . The shr mutant demonstrated reduced hemoglobin binding, though cell growth in iron-depleted medium supplemented with hemoglobin, whole blood, or ferric citrate was not affected, suggesting additional systems are involved in hemoglobin utilization . SiaA and Shr are the first hemoprotein receptors identified in S . pyogenes; their possible role in iron capture is discussed. Infect Immun, 2003 Mar, 71(3), 1033 - 41 Regions of PspA/EF3296 best able to elicit protection against Streptococcus pneumoniae in a murine infection model; Roche H et al.; Pneumococcal surface protein A (PspA) can elicit protection against Streptococcus pneumoniae in mouse infection models . PspA is classified by serology and amino acid sequence into two major families that are divided by sequence into five clades . The most variable portion of the molecule is the alpha-helical domain, which comprises the N-terminal half of PspA . Prior studies of a family 1 PspA protein observed that protective antibodies are reactive with epitopes in the alpha-helical domain and that most cross-protective epitopes mapped to the 108 most C-terminal amino acids of the alpha-helical region . In these studies, we have used six overlapping recombinant fragments of family 2, clade 3 PspA/EF3296 to map the protection-eliciting regions of its alpha-helical domain . The three fragments, which included the 104 most C-terminal amino acids of the alpha-helical domain (314 to 418), could each elicit protection against EF3296 . A fragment comprising amino acids 75 to 305 failed to elicit significant protection . A fragment containing amino acids 1 to 115 elicited protection against EF3296 in BALB/c mice but not in CBA/N mice . All three fragments containing amino acids 314 to 418 were able to elicit cross-protection against pneumococci expressing PspA proteins of clades 2, 3, 4, and 5 . Cross-protection elicited by these three fragments was easier to demonstrate in CBA/N mice than in BALB/c mice . The 1-to-115 fragment, however, elicited some cross-protection against clades 2 and 4 in BALB/c mice but not in CBA/N mice . These studies provide support for the importance of the C-terminal 104 and N-terminal 115 amino acids of the alpha-helical region of PspA in the elicitation of cross-protection. J Immunol, 2003 Mar 1, 170(5), 2274 - 8 Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide; Di Nardo A et al.; Cathelicidins (caths) are peptides that are expressed at high levels in neutrophils and some epithelia and can act as natural antibiotics by directly killing a wide range of microorganisms . We hypothesized that caths are expressed in mast cells (MCs), because these cells have been previously associated with inherent antimicrobial activity . Cultured murine MCs contained abundant amounts of cathelin-related antimicrobial peptide (AMP), the murine cath, and this expression was inducible by LPS or lipoteichoic acid . Human skin MCs also expressed cath as detected by immunohistochemical analysis for the human cath LL-37 . The functional significance of this expression was shown by comparing MCs cultured from normal mice to MCs from littermates deficient in the cathelin-related AMP gene (Cnlp(-)) . MCs derived from Cnlp(-/-) animals had a 50% reduction in their ability to kill group A STREPTOCOCCUS: These MCs expressed equivalent amounts of mRNA for murine beta-defensin-4, a beta-defensin AMP . Thus, different antimicrobials can be identified in MCs, and the presence of cath is necessary for efficient bacterial killing . These observations suggest that the presence of cath is vital to the ability of mammali