J Infect Dis, 1999 Feb, 179(2), 403 - 13 Self heat-shock protein (hsp60) peptide serves in a conjugate vaccine against a lethal pneumococcal infection; Konen-Waisman S et al.; Healthy persons manifest a high frequency of T cells reactive to epitopes of the self 60-kDa heat-shock protein (hsp60) molecule . It was reasoned that a self hsp60 peptide, p458m, might provide T cell help for a response to the T independent capsular polysaccharide of Streptococcus pneumoniae type 4 (PS4) . The conjugate vaccine (PS4-p458m) induced resistance to challenge with >300,000 times the minimal lethal dose of pneumococci . PS4 conjugated to other immunogenic carriers (tetanus toxoid, a pneumolysin peptide, and others) or a commercial pneumococcal vaccine were far less effective . The effectiveness of the PS4-p458m conjugate was associated with an increased IgG1 antibody response to PS4, with long-term memory, and with T cell responses to the p458m peptide . Thus, T cell reactivity to a self epitope in a conjugate vaccine can be mobilized to induce help for resistance to a lethal infection. EMBO J, 1999 Jan 4, 18(1), 9 - 21 Structural basis for the recognition of superantigen streptococcal pyrogenic exotoxin A (SpeA1) by MHC class II molecules and T-cell receptors; Papageorgiou AC et al.; Streptococcal pyrogenic exotoxin A (SpeA) is a superantigen produced by Streptococcus pyogenes and is associated with severe infections characterized by rash, hypotension, multiorgan failure and a high mortality rate . In this study, an allelic form of this toxin, SpeA1, was crystallized with four molecules in the crystallographic asymmetric unit and its crystal structure was determined at 2.6 A resolution . The crystallographic R-factor was 19.4% (33 497 reflections) for 7031 protein atoms and 88 water molecules . The overall structure of SpeA1 is considerably similar to that of other prototype microbial superantigens, either of staphylococcal or streptococcal origin, but has greatest similarity to staphylococcal enterotoxin C (SEC) . Based on structural and mutagenesis data, we have mapped several important residues on the toxin molecule, which are involved in the recognition of major histocompatibility complex (MHC) class II molecules and T-cell receptors . Also, the toxin appears to possess a potential zinc-binding site which may have implications in binding to particular MHC class II molecules . Finally, we propose models for SpeA1-MHC class II and SpeA1-T-cell receptor association and the relevance of this phenomenon to the superantigenic action of this toxin is considered. Arch Oral Biol, 1998 Dec, 43(12), 917 - 24 The effects of fluoride concentration and the level of cariogenic challenge on caries development in desalivated rats; Tabchoury CM et al.; Dental caries is an infectious and transmissible disease that continues to affect the majority of people . The presence of carbohydrate, mainly sucrose in the diet, is an important factor in its occurrence . The amount of fluoride required for optimal protective effect where there is a high caries challenge is unclear . Differences in the intensity of cariogenic challenge, for whatever reason, may play a part in determining fluctuations in the effectiveness of fluoride . The purpose of this study was to evaluate the effect of different concentrations of fluoride on the development of caries and explore the cariostatic effect of fluoride under various levels of cariogenic challenge . The study comprises two experiments . In experiment I, 60 desalivated Sprague Dawley rats infected with Streptococcus sobrinus were offered the following to drink for 21 days: group (1), sterile distilled water (SDW); (2) 10 parts/10(6) F SDW; (3) 20 parts/10(6) F SDW; (4) 30 parts/10(6) F SDW; (5) 40 parts/10(6) F SDW . In experiment II, eight groups of 9 rats were placed in a Konig Hofer programmed feeder and were exposed to different levels of cariogenic challenge through varying frequency of eating and offered water containing 10 parts/10(6) F . In experiment I, exposure to 20, 30 and 40 parts/10(6) F reduced caries development significantly: fluoride, at 10 parts/10(6), reduced the severity of the carious lesions . In this model of severe cariogenic challenge, the results suggest that elevated concentrations of fluoride might be effective in patients at high caries risk . In experiment II, fluoride reduced the incidence and severity of smooth-surface caries in all groups . The protective effect of fluoride decreased as the number of exposures to sugar increased . It is concluded that the effectiveness of fluoride is influenced by the level of cariogenic challenge and that consideration should be given to adjusting the level of fluoride exposure based on perceived caries risk, and that there is a maximum therapeutic effect of fluoride beyond which no additional protection can be expected. J Med Microbiol, 1998 Aug, 47(8), 711 - 5 Expression of heat-shock proteins in Streptococcus pyogenes and their immunoreactivity with sera from patients with streptococcal diseases; Lemos JA et al.; The heat-shock response of Streptococcus pyogenes following exposure to elevated growth temperatures, and the immunological reactivity of heat-shock proteins (HSPs) in streptococcal infections were studied . Two major proteins of 65 and 75 kDa were expressed when a S . pyogenes strain was shifted from 37 degrees C to heat-shock temperatures of 40, 42 and 45 degrees C . Such proteins are members of the GroEL and DnaK families recognised in a Western blot assay with polyclonal antibodies against Escherichia coli GroEL and E . coli DnaK, respectively . Two-dimensional autoradiograms of polypeptides labelled at 37 or 42 degrees C showed an increased intensity of three spots at 42 degrees C . A monoclonal antibody (MAb) against HSP 63 of Bordetella pertussis also recognised the 65-kDa inducible protein, although MAbs against Mycobacterium tuberculosis HSP 65 failed to recognise this protein . Immunoblot analysis of sera from individuals with rheumatic fever or uncomplicated streptococcal diseases revealed seven major immunogenic protein bands, two of which also reacted with anti-E . coli GroEL and DnaK polyclonal antibodies . Furthermore, antibodies to the GroEL and DnaK proteins were also detected in sera from patients with either rheumatoid arthritis or systemic lupus erythematosus . These results demonstrated a heat-shock response of S . pyogenes, and indicated the presence of an immune response against HSPs in streptococcal diseases. J Mass Spectrom, 1998 Dec, 33(12), 1182 - 91 Structures of biologically active muramyl peptides from peptidoglycan of Streptococcus sanguis; Beranova-Giorgianni S et al.; The structures of major muramyl peptides derived from peptidoglycan of the oral pathogen Streptococcus sanguis were determined and the biological activity of the peptides was tested in vitro on human monocytes . The muramyl peptides, produced by muramidase digestion of the purified peptidoglycan, were separated by reversed-phase high-performance liquid chromatography, either in their native form or after reduction with sodium borohydride . Chemical structures of the peptides were elucidated by a combination of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, amino acid analysis, post-source decay analysis and Edman sequencing . The study revealed two distinct monomers: N-acetylglucosaminyl-N-acetylmuramyl-Ala-iGln-Lys(Ala-Ala) (1), where the Ala-Ala is connected to the epsilon-amino group of lysine, and N-acetylglucosaminyl-N-acetylmuramyl-Ala-iGln-Lys(Ala-Ala)-Ala-Ala (2), where an additional dialanyl residue is attached to the lysine alpha-carboxyl group . Two sets of higher oligomers (di-, tri- and tetramers), related structurally to monomers 1 or 2 were also detected . In these oligomers, the monomeric subunits are linked together by Ala-Ala-Ala bridges . The native muramyl peptides primed human monocytes in vitro for the increased production of the microbicidal superoxide radical. Proc Natl Acad Sci U S A, 1999 Jan 5, 96(1), 242 - 7 A natural variant of the cysteine protease virulence factor of group A Streptococcus with an arginine-glycine-aspartic acid (RGD) motif preferentially binds human integrins alphavbeta3 and alphaIIbbeta3; Stockbauer KE et al.; The human pathogenic bacterium group A Streptococcus produces an extracellular cysteine protease {streptococcal pyrogenic exotoxin B (SpeB)} that is a critical virulence factor for invasive disease episodes . Sequence analysis of the speB gene from 200 group A Streptococcus isolates collected worldwide identified three main mature SpeB (mSpeB) variants . One of these variants (mSpeB2) contains an Arg-Gly-Asp (RGD) sequence, a tripeptide motif that is commonly recognized by integrin receptors . mSpeB2 is made by all isolates of the unusually virulent serotype M1 and several other geographically widespread clones that frequently cause invasive infections . Only the mSpeB2 variant bound to transfected cells expressing integrin alphavbeta3 (also known as the vitronectin receptor) or alphaIIbbeta3 (platelet glycoprotein IIb-IIIa), and binding was blocked by a mAb that recognizes the streptococcal protease RGD motif region . In addition, mSpeB2 bound purified platelet integrin alphaIIbbeta3 . Defined beta3 mutants that are altered for fibrinogen binding were defective for SpeB binding . Synthetic peptides with the mSpeB2 RGD motif, but not the RSD sequence present in other mSpeB variants, blocked binding of mSpeB2 to transfected cells expressing alphavbeta3 and caused detachment of cultured human umbilical vein endothelial cells . The results (i) identify a Gram-positive virulence factor that directly binds integrins, (ii) identify naturally occurring variants of a documented Gram-positive virulence factor with biomedically relevant differences in their interactions with host cells, and (iii) add to the theme that subtle natural variation in microbial virulence factor structure alters the character of host-pathogen interactions. Ann Thorac Surg, 1998 Nov, 66(5), 1818 - 9 Homograft failure in mycotic aortic aneurysm caused by Streptococcus pneumoniae; Berdat PA et al.; Treatment of a rare Streptococcus pneumoniae mycotic aneurysm by homograft replacement failed in a 59-year-old patient because of persistent lobar pneumonia . Despite reoperation with replacement of the infected homograft by a fresh one, he finally died of septicemia . This case illustrates that homograft tissue may be infected per continuum and that extensive debridement of periaortic tissue-including major lung resection-and the use of muscle flaps may be necessary in certain circumstances. Arch Pharm Res, 1998 Jun, 21(3), 348 - 52 Antibacterial activity of Camellia sinensis extracts against dental caries; Rasheed A et al.; Different bacteria were separated from saliva and teeth of cariogenic patients and identified by a variety of morphological and biochemical tests . Extracts of green tea strongly inhibited Escherichia coli, Streptococcus salivarius and Streptococcus mutans . The antibacterial effect of green and black tea extracts were compared with those of amoxicillin, cephradine and eugenol. Clin Diagn Lab Immunol, 1999 Jan, 6(1), 50 - 4 Transplacental transmission of serotype-specific pneumococcal antibodies in a Brazilian population; Carvalho BT et al.; The highest incidence of severe pneumococcal infections in children occurs in the first 6 months of life; however, immunization of infants with the existing polysaccharide vaccines is ineffective . We wished to determine the prevalence of immunoglobulin G (IgG) pneumococcal antibodies in unimmunized Brazilian mothers and their transplacental transmission to term and preterm infants . Total IgG, IgG1 and -2 subclass levels, and IgG antibodies against Streptococcus pneumoniae serotypes 1, 3, 6B, 9V, and 14 were determined in 15 pairs of mothers and term newborns (gestational age, >/=37 weeks) and in 18 pairs of mothers and preterm newborns (gestational age, 32 to 36 weeks) . Serotype-specific anti-pneumococcal antibodies were detected by a recently standardized enzyme-linked immunosorbent assay calibrated with the 89-SF reference serum . Varying percentages of the mothers had antibody concentrations below arbitrarily defined protective levels: 33% for serotype 1, 67% for serotype 3, 30% for serotype 6B, 52% for serotype 9V, and 22% for serotype 14 . In term newborns, IgG1 concentrations were slightly higher than maternal concentrations; in preterm newborns, the concentrations were much lower . Concentrations of IgG2 in term and preterm infants were significantly lower than in the mothers . Transplacental transmission of antibodies to serotypes 3 and 14 was clearly different from that of antibodies to serotypes 1, 6B, and 9V . Concentrations of IgG antibodies against serotypes 3 and 14 were similar to or higher than those of the mothers; against serotypes 1, 6B, and 9V they ranged from 77 to 83% of maternal concentrations in term newborns and also in preterm infants, although transplacental transmission of antibodies was proportionally lower for each specific serotype in preterm than in term infants . These data are relevant for developing strategies to protect infants against pneumococcal infections in the first months of life . Our findings and a review of existing information stress the importance of understanding the relationships among pneumococcal immunization, IgG subclass antibodies to individual serotypes, transplacental transport, half-life, and antibody function and their protective values against infection. J Exp Med, 1999 Jan 4, 189(1), 89 - 102 Identification and characterization of novel superantigens from Streptococcus pyogenes; Proft T et al.; Three novel streptococcal superantigen genes (spe-g, spe-h, and spe-j) were identified from the Streptococcus pyogenes M1 genomic database at the University of Oklahoma . A fourth novel gene (smez-2) was isolated from the S . pyogenes strain 2035, based on sequence homology to the streptococcal mitogenic exotoxin z (smez) gene . SMEZ-2, SPE-G, and SPE-J are most closely related to SMEZ and streptococcal pyrogenic exotoxin (SPE)-C, whereas SPE-H is most similar to the staphylococcal toxins than to any other streptococcal toxin . Recombinant (r)SMEZ, rSMEZ-2, rSPE-G, and rSPE-H were mitogenic for human peripheral blood lymphocytes with half-maximal responses between 0.02 and 50 pg/ml (rSMEZ-2 and rSPE-H, respectively) . SMEZ-2 is the most potent superantigen (SAg) discovered thus far . All toxins, except rSPE-G, were active on murine T cells, but with reduced potency . Binding to a human B-lymphoblastoid line was shown to be zinc dependent with high binding affinity of 15-65 nM . Evidence from modeled protein structures and competitive binding experiments suggest that high affinity binding of each toxin is to the major histocompatibility complex class II beta chain . Competition for binding between toxins was varied and revealed overlapping but discrete binding to subsets of class II molecules in the hierarchical order (SMEZ, SPE-C) > SMEZ-2 > SPE-H > SPE-G . The most common targets for the novel SAgs were human Vbeta2.1- and Vbeta4-expressing T cells . This might reflect a specific role for this subset of Vbetas in the immune defense of gram-positive bacteria. Eur J Biochem, 1998 Dec 1, 258(2), 897 - 905 Multiple specificities of the staphylococcal and streptococcal fibronectin-binding microbial surface components recognizing adhesive matrix molecules; Joh D et al.; Many pathogenic gram-positive bacteria express fibronectin (Fn)-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), most of which have a similar structural organization with a primary ligand-binding domain consisting of 3-6 repeats of 40-50 amino-acid-residue motifs . The MSCRAMMs appear to preferentially bind to the N-terminal region of Fn, which is composed of five type-I modules . Here we report that the Fn-binding MSCRAMM FnbpA of Staphylococcus aureus contains a second ligand-binding domain located outside the repeat units . In addition, several sites in the Fn N-terminus presented as recombinant type-I module pairs bind to the repeat domain of the MSCRAMM . All of the MSCRAMMs analyzed, which include FnbpA of Staphylococcus aureus, Sfb of Streptococcus pyogenes, and FnbA and FnbB of Streptococcus dysgalactiae, were shown to bind to multiple sites in the N-terminal domain of Fn . By dissecting the repeat domain of FnbpA using synthetic peptides and recombinant fragments, we show that discrete, different motifs are responsible for the binding to individual sites in Fn, rather than a common motif being able to bind to several pairs of type-I Fn modules . The C-terminal half of many of the MSCRAMM repeat units contain a common motif, which is shown here to bind to the type-I module pair 4 and 5 . In addition, some of the repeat units of FnbpA contain N-terminal motifs which bound to the type-I module pairs 1-2 and 2-3, respectively . These latter binding motifs appear to be partly overlapping and dependent on flanking sequences . Fluorescence polarization experiments using fluorescein-labeled MSCRAMM peptides and recombinant type-I Fn module pairs revealed dissociation constants of 1-13 microM . It was also shown that the fluorescein-labeled peptides differed in their primary binding sites on Fn. Am J Respir Crit Care Med, 1999 Jan, 159(1), 188 - 98 Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury . Incidence, risk factors, and association with ventilator-associated pneumonia; Ewig S et al.; We prospectively evaluated the relation of upper airway, lower airway, and gastric colonization patterns with the development of pneumonia and its etiology in 48 patients with surgical (n = 25) and medical (n = 23) head injury . Initial colonization was assessed by cultures of nasal and pharyngeal swabs, tracheobronchial aspirates, gastric juice, and bronchoscopically retrieved protected specimen brush . Follow-up colonization was determined until the end points extubation, suspected ventilator-associated pneumonia (VAP), or death . The initial colonization rate at any site at ICU admission was 39/47 (83%) . It mainly accounted for Group I pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae) of the upper and lower airways . At follow-up, colonization rates with Group II pathogens (Gram-negative enteric bacilli and Pseudomonas spp.) increased significantly . The high initial bacterial load with Group I pathogens of the upper airways and trachea decreased during Days 2 to 4, whereas that of Group II pathogens increased . Upper airway colonization was an independent predictor of follow-up tracheobronchial colonization (odds ratio {OR}, 9.9; 95% confidence interval {CI}, 1.8 to 56.3 for initial colonization with Group I pathogens; OR, 23.9; 95% CI, 3.8 to 153.3 for follow-up colonization with Group II pathogens) . Previous (short-term) antibiotics had a protective effect against colonization with Group I pathogens of the lower respiratory tract (OR, 0.2; 95% CI, 0.05 to 0.86), but they were a risk factor for colonization with Group II pathogens (OR, 6.1; 95% CI, 1.3 to 29) . Initial tracheobronchial colonization with Group I pathogens was associated with a higher probability of early onset pneumonia (OR, 4 . 1; 95% CI, 0.7 to 23.3), whereas prolonged antibiotic treatment (> 24 h) independently predicted late-onset pneumonia (OR, 9.2; 95% CI, 1.7 to 51.3) . We conclude that patients with head injury are colonized in the airways mainly by Group I pathogens early in the evolution of illness . The upper airways represent the main reservoir for subsequent lower airway colonization with Group I pathogens . Previous (short-term) antibiotic treatment is protective against initial tracheobronchial colonization with Group I pathogens, but it represents a risk factor for subsequent lower airway colonization by Group II pathogens. Appl Environ Microbiol, 1999 Jan, 65(1), 6 - 10 Fate of free DNA and transformation of the oral bacterium Streptococcus gordonii DL1 by plasmid DNA in human saliva; Mercer DK et al.; Competitive PCR was used to monitor the survival of a 520-bp DNA target sequence from a recombinant plasmid, pVACMC1, after admixture of the plasmid with freshly sampled human saliva . The fraction of the target remaining amplifiable ranged from 40 to 65% after 10 min of exposure to saliva samples from five subjects and from 6 to 25% after 60 min of exposure . pVACMC1 plasmid DNA that had been exposed to degradation by fresh saliva was capable of transforming naturally competent Streptococcus gordonii DL1 to erythromycin resistance, although transforming activity decreased rapidly, with a half-life of approximately 50 s . S . gordonii DL1 transformants were obtained in the presence of filter-sterilized saliva and a 1-microg/ml final concentration of pVACMC1 DNA . Addition of filter-sterilized saliva instead of heat-inactivated horse serum to S . gordonii DL1 cells induced competence, although with slightly lower efficiency . These findings indicate that DNA released from bacteria or food sources within the mouth has the potential to transform naturally competent oral bacteria . However, further investigations are needed to establish whether transformation of oral bacteria can occur at significant frequencies in vivo. Oral Microbiol Immunol, 1998 Dec, 13(6), 387 - 9 Purification and properties of a bacteriocin of Staphylococcus epidermidis isolated from dental plaque; Nakamura T et al.; An extracellular bacteriocin of Staphylococcus epidermidis isolated from dental plaque was purified and characterized . Its molecular mass was 3500 Da and pI was 10.5 . This bacteriocin inhibited the growth of Staphylococcus aureus, Streptococcus salivarius, and Streptococcus mitis, but Streptococcus mutans, Streptococcus sanguis and other oral indigenous bacterial species examined were not inhibited . The mode of inhibition was found to be bacteriostatic. Oral Microbiol Immunol, 1998 Dec, 13(6), 382 - 6 Detection of dextranase-producing gram-negative oral bacteria; Igarashi T et al.; Thirty-one strains of 23 gram-negative oral bacterial species were examined for dextran-degrading activity on agar plates containing blue dextran . One strain each of Capnocytophaga ochracea, Capnocytophaga sputigena, Prevotella loescheii, Prevotella melaninogenica and Prevotella oralis had detectable dextranase activity . The culture supernatants of P . melaninogenica and P . oralis cells contained dextranases of multiple sizes, but those of the other three species had a single size of enzyme . A 56-kDa dextranase was purified from the culture supernatant of P . oralis and the antiserum against the enzyme was prepared with a rabbit . The Ouchterlony test showed that the antibody reacted with the supernatants of both P . melaninogenica and P . oralis but not with the others . Dot-blot hybridization using the dextranase gene of Streptococcus mutans as a probe revealed that there was no significantly homologous sequence in the chromosomal DNA of the five species. Oral Microbiol Immunol, 1998 Dec, 13(6), 378 - 81 Combined inhibitory effect of bovine immune whey and peroxidase-generated hypothiocyanite against glucose uptake by Streptococcus mutans; Loimaranta V et al.; Immune whey product was obtained from Streptococcus mutans- and Streptococcus sobrinus-immunized cows . Hypothiocyanite (HOSCN/OSCN-) was generated in VMG-buffer, pH 5.5 or 6.5, by bovine milk lactoperoxidase, KSCN and hydrogen peroxide . The glucose incorporation by late-log cells of S . mutans 10449, serotype c, was followed by measuring the uptake of 14C-glucose at 37 degrees C . At pH 5.5 and 6.5 both immune whey product and HOSCN/OSCN- dose-dependently inhibited glucose uptake . The inhibition by their combination was additive if bacterial cells were treated with HOSCN/OSCN- before exposed to immune whey product . In contrast to immune whey product, the control product from sham-immunized cows increased the glucose uptake even when added simultaneously with HOSCN/OSCN- . However, when bacterial cells were pretreated with HOSCN/OSCN- an enhanced inhibitory effect was observed also with control product . The results indicate that colostral proteins from S . mutants- or S . sobrinus-immunized cows inhibit glucose uptake and that the effect is enhanced by pretreatment with lactoperoxidase-generated HOSCN/OSCN-. J Cutan Pathol, 1998 Nov, 25(10), 538 - 44 A distinctive cutaneous reaction pattern indicative of infection by reactive arthropathy-associated microbial pathogens: the superantigen ID reaction; Magro CM et al.; The two major cutaneous expressions of infective states are infections of the skin by viable organisms and immunological responses to nonviable microbial antigens or, in the case of molecular mimickry, their human analogues . These immunological responses are designated as cutaneous id reactions, and manifest a histomorphology similar to that seen at the primary infective site . This study presents the clinical and histological findings in 16 patients who developed skin eruptions associated with extracutaneous or systemic infections . There was a striking female predominance; patients ranged in age from 10 to 78 years . The majority of cases manifested skin lesions which clinically resembled Sweet's syndrome, erythema multiforme and/or erythema nodosum . Fever, arthralgia, oligoarthritis, mucosal ulcers of the mouth and/ or genital tract and uveitis were additional features in some cases . Isolated clinical presentations included a petechial rash in a stocking and glove distribution, papular dermatitis, a morbilliform eruption and annular erythema . Among the medical and family histories were atopy and stigmata associated with connective tissue disease (CTD) . Two patients were ingesting drugs with known immune dysregulating properties . Skin biopsies showed focal lymphocytic interface dermatitis, a diffuse interstitial histiocytic infiltrate, and a mononuclear cell predominant vascular reaction which in some cases represented vasculitis by virtue of manifesting concomitant luminal or mural fibrin deposition . Eosinophils, eczematous alterations, and papillary dermal edema were identified in a minority of cases . All patients had evidence of a prior or concurrent infection, based on either positive IgM serology for specific microbes or cultures . Among the implicated pathogens were cytomegalovirus, parvovirus B19, streptococcus, mycoplasma, klebsiella, and Borrelia burgdorferi . All of these organisms are among those associated with reactive arthritis, a phenomenon that was seen in some cases . The histology suggested florid cell mediated immunity (CMI), which the authors attributed to the superantigen properties held by the aforesaid pathogens . Skin lesions and constitutional symptoms resolved quickly with antimicrobial therapy in 7 of 9 cases causally linked to bacteria . Spontaneous resolution occurred in 5 of 6 virally mediated eruptions . The other 4 patients were given topical steroids or prednisone; these included 1 patient with Borrelia burgdorferi infection and 1 patient with radiographic evidence of pneumonia who was never cultured, 1 patient with parvovirus B19 infection, and 1 patient with pneumococcal pneumonia and concomitant sarcoidosis . It is the authors' belief that the eruptions seen in these patients may in part reflect a genetic or iatrogenic predisposition to respond excessively to certain infectious triggers. Obstet Gynecol Surv, 1998 Dec, 53(12), 737 - 40 Listeriosis during pregnancy; Silver HM; Listeriosis is an uncommon infection that has a unique predilection for pregnant women and may result in pregnancy loss . Contaminated food is the usual source of infection, and increased federal surveillance of foodstuffs is the most effective strategy for prevention of disease . Although dramatic epidemics have received the most publicity, more cases of perinatal listeriosis are isolated . If Listeria chorioamnionitis is diagnosed preterm, in contrast to other types of chorioamnionitis, in utero therapy with high-dose penicillin or trimethoprim-sulfamethoxazole is possible, and preterm delivery may be avoided . The clinical characteristics of neonatal listeriosis are similar to neonatal Group B Streptococcus sepsis, with early and late onset forms of disease . The epidemiology, diagnosis, and management of Listeria infection in pregnancy are reviewed. Antimicrob Agents Chemother, 1999 Jan, 43(1), 187 - 9 Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae; Gill MJ et al.; An open reading frame (ORF) homologous to norA was insertionally inactivated with cat in a fluoroquinolone-resistant pneumococcus with an efflux phenotype; this inactivation caused reversion to drug sensitivity . The ORF product has 24% amino acid sequence identity each to NorA and Bmr, which suggests that it is a major facilitator system pump of the 12-transmembrane-segment class. Antimicrob Agents Chemother, 1999 Jan, 43(1), 35 - 40 Efficacy of high-dose amoxicillin-clavulanate against experimental respiratory tract infections caused by strains of Streptococcus pneumoniae; Woodnutt G et al.; The purpose of the present investigation was to determine if the efficacy of amoxicillin-clavulanate against penicillin-resistant Streptococcus pneumoniae could be improved by increasing the pediatric amoxicillin unit dose (90 versus 45 mg/kg of body weight/day) while maintaining the clavulanate unit dose at 6.4 mg/kg/day . A rat pneumonia model was used . In that model approximately 6 log10 CFU of one of four strains of S . pneumoniae (amoxicillin MICs, 2 microg/ml {one strain}, 4 microg/ml {two strains}, and 8 microg/ml {one strain}) were instilled into the bronchi of rats . Amoxicillin-clavulanate was given by computer-controlled intravenous infusion to approximate the concentrations achieved in the plasma of children following the administration of oral doses of 45/6.4 mg/kg/day or 90/6.4 mg/kg/g/day divided every 12 h or saline as a control for a total of 3 days . Infusions continued for 3 days, and 2 h after the cessation of infusion, bacterial numbers in the lungs were significantly reduced by the 90/6.4-mg/kg/day equivalent dosage for strains for which amoxicillin MICs were 2 or 4 microg/ml . The 45/6.4-mg/kg/day equivalent dosage was fully effective only against the strain for which the amoxicillin MIC was 2 microg/ml and had marginal efficacy against one of the two strains for which amoxicillin MICs were 4 microg/ml . The bacterial load for the strain for which the amoxicillin MIC was 8 microg/ml was not reduced with either dosage . These data demonstrate that regimens which achieved concentrations in plasma above the MIC for at least 34% of a 24-h dosing period resulted in significant reductions in the number of viable bacteria, indicating that the efficacy of amoxicillin-clavulanate can be extended to include efficacy against less susceptible strains of S . pneumoniae by increasing the amoxicillin dose. Antimicrob Agents Chemother, 1999 Jan, 43(1), 29 - 34 Two pharmacodynamic models for assessing the efficacy of amoxicillin-clavulanate against experimental respiratory tract infections caused by strains of Streptococcus pneumoniae; Woodnutt G et al.; Two models of respiratory tract infection were used to investigate the pharmacodynamics of amoxicillin-clavulanate against Streptococcus pneumoniae . Eight strains of S . pneumoniae were used in a mouse model in which the animals were infected intranasally and were then treated with a range of doses and dose intervals . The time that the plasma amoxicillin concentration remained above the MIC (T>MIC) correlated well with bacterial killing, such that if T>MIC was below 20% there was no effect on bacterial numbers in the lungs . As T>MIC increased, the response, in terms of decreased bacterial load, improved and at T>MICs of greater than 35 to 40% of the dosing interval, bacteriological cure was maximal . On the basis of equivalent T>MICs, these data would suggest that in humans a dosage of 500 mg three times daily (t.i.d.) should have efficacy equal to that of a dosage of 875 mg twice daily (b.i.d.) . This hypothesis was evaluated in a rat model in which amoxicillin-clavulanate was given by computer-controlled intravenous infusion to achieve concentrations that approximate the concentrations achieved in the plasma of humans following oral administration of 500/125 mg t.i.d . or 875/125 mg b.i.d . Infusions continued for 3 days and bacterial numbers in the lungs 2 h after the cessation of the infusion were significantly reduced (P < 0.01) by both treatments in strains of S . pneumoniae for which amoxicillin MICs were below 2 microg/ml . When tested against a strain of S . pneumoniae for which the amoxicillin MIC was 4 microg/ml, the simulated 500/125-mg dose was ineffective but the 875/125-mg dose demonstrated a small but significant (P < 0 . 01) reduction in bacterial numbers . These data confirm the findings in the mouse and indicate that amoxicillin-clavulanate administered at 875/125 mg b.i.d . would be as effective clinically as amoxicillin-clavulanate administered at 500/125 mg t.i.d. Orv Hetil, 1998 Nov 29, 139(48), 2899 - 901 {Intrapartum administration of antibiotics in the prevention of neonatal Streptococcus B infections}; Horvath B et al.; This study was performed prospectively . Between 1 . January 1995 and 31 December 1997, a modification of the screening-based strategy protocol was implemented . Antenatal screening cultures for GBS were performed at approximately 30-32 weeks of gestation . The protocol recommends the use of antibiotic prophylaxis to GBS positive women with any of the obstetric risk factors for early-onset of GBS disease . Our regiment for prophylaxis for patients in labor was ampicillin 2 g . intravenously then 1 g . i.v . every 4 hours until delivery . Before this study had started (1984-1994), there were 149 serious neonatal GBS infection (149/15,040 pregnancy, among them were 97 premature infants . Thirty-one infants suffered from connatal sepsis . We observed 29 lethal infection . Between January 01, 1995, and December 31, 1997, 4150 women participated in this investigation . The incidence of positive group B Streptococcus cultures from the vaginal samples was 11.6% (481/4150) . During the study period (3 years), serious GBS infection was detected in 46 infants (1.1%) . There were 9 cases of neonatal sepsis (0.2%), two of them suffered lethal infections (0.05%) . There was no late onset of GBS disease and lethal outcome in the last two years . Our investigations bears clinical importance because we confirmed that group B streptococcal colonization is an important risk factor for neonatal infection . The selective intrapartum chemoprophylaxis is a safe and effective intervention to prevent early-onset severe GBS disease. FEMS Microbiol Lett, 1998 Dec 15, 169(2), 355 - 9 Uptake and incorporation of choline and ethanolamine into lipoteichoic acid and teichoic acid by the choline-independent mutant JY2190 of Streptococcus pneumoniae; Leopold K et al.; Lipoteichoic acid- and teichoic acid-containing muropeptides were isolated from choline- or ethanolamine-grown cells of the choline-independent mutant JY2190 of Streptococcus pneumoniae . Choline was taken up and incorporated into lipoteichoic acid and teichoic acid with 81% efficiency, compared with the parent strain Rx1 . With similar efficiency, ethanolamine was incorporated . Accordingly, the mutant is a valuable tool for identifying the individual genes encoding the enzymes of choline utilisation, because any of these genes can be deleted without affecting viability and growth rate. Clin Infect Dis, 1998 Dec, 27(6), 1442 - 50 Serotype distribution and prevalence of resistance to benzylpenicillin in three representative populations of Streptococcus pneumoniae isolates from the coast of Kenya; Scott JA et al.; As surveillance data from sub-Saharan Africa are few, three representative populations of Streptococcus pneumoniae isolates were examined in Kenya for serotype distribution and Etest minimum inhibitory concentrations (MICs) of benzylpenicillin: (1) 75 lung aspirate or blood culture isolates from 301 consecutive adult patients with pneumonia, (2) 112 invasive isolates from continuous pediatric inpatient surveillance over 4 years, and (3) 97 nasopharyngeal isolates from systematically selected sick children . The proportions with benzylpenicillin MICs of > or = 0.1 microgram/mL were 0.27, 0.29, and 0.47, respectively . Vaccine-related serotypes accounted for 96% of invasive isolates from children and 90% of those from human immunodeficiency virus (HIV)-seropositive adults . Serotype 1 accounted for 44% of pneumococci from HIV-seronegative patients but only 5% of those from HIV-seropositive patients (P = .0002) . Of serotype 1 isolates, 98% were susceptible to benzylpenicillin, but serogroups 13, 14, 19, and 23 were strongly associated with an MIC of > or = 0.1 microgram/mL. Clin Infect Dis, 1998 Dec, 27(6), 1428 - 36 Epidemiological and clinical aspects of invasive group A streptococcal infections and the streptococcal toxic shock syndrome; Eriksson BK et al.; In a retrospective study of invasive infections due to group A Streptococcus (GAS) in Stockholm during 1987 to 1995, the average incidence per 100,000 residents per year was 2.3, varying between 3.7 per 100,000 (in 1988) and 1.3 per 100,000 (in 1993) . Incidence was 1.8 in the age group of 0-4 years but otherwise increased by age, from 0.48 in the age group of 5-14 years to 6.1 among those over 65 years of age . A review of 151 invasive episodes occurring in 1983-1995 showed cyclic increases of infections due to T1M1-serotype strains during 1986-1990 and 1993-1995 . The T1M1 serotype accounted for 27 (20%) of 135 available GAS strains . Streptococcal toxic shock syndrome (STSS) developed in 19 (13%) of the 151 episodes . The case fatality rate was 11% overall but 47% among patients with STSS . In a multivariate logistic regression model, STSS was associated with a history of alcohol abuse (odds ratio {OR}, 6.3; P = .004) and infection with a T1M1 strain (OR, 6.7; P = .007) . Case fatality was associated with age (OR, 14.5; P = .08), immunosuppression (OR, 4.7; P = .02), and STSS (OR, 21.5; P < .0001) but not with T1M1 infection . Hypotension was significantly associated with a fatal outcome, regardless of whether STSS developed (P < .0001). Am J Epidemiol, 1998 Dec 15, 148(12), 1212 - 8 Geocoding and linking data from population-based surveillance and the US Census to evaluate the impact of median household income on the epidemiology of invasive Streptococcus pneumoniae infections; Chen FM et al.; The emergence of drug-resistant Streptococcus pneumoniae poses new clinical challenges and may also reflect a change in the epidemiology of S . pneumoniae infections . A variety of studies have shown that drug-resistant S . pneumoniae infections are linked to antimicrobial use . It has been hypothesized that persons of high socioeconomic status are at increased risk for a drug-resistant infection because of greater access to antimicrobial drugs . To assess whether median household income is associated with increased risk of penicillin-nonsusceptible S . pneumoniae infections, the authors geocoded and linked data from population-based surveillance for invasive pneumococcal disease with data from the 1990 US Census . Among invasive pneumococcal isolates from Atlanta, Georgia, in 1994, increasing proportions of penicillin-nonsusceptible isolates were associated with higher median household incomes (chi2 for trend, 15.17; p=0.002) . Despite higher rates of invasive pneumococcal disease among blacks and persons who resided within lower median household income areas, white patients in areas with higher median household income had a higher risk of being infected with strains that were not susceptible to penicillin (Wilcoxon rank sum, Z=2.66, p=0.008) . These findings demonstrated the utility of geocoding and US Census data in describing the epidemiology of drug-resistant S . pneumoniae and also provided more evidence that socioeconomic factors may influence the development of drug resistance. Indian J Pathol Microbiol, 1998 Oct, 41(4), 437 - 41 Diabetic foot infections: a study of microorganisms associated with the different Wagner grades; Pathare NA et al.; Patients with diabetes foot infections were evaluated over a two year period to assess the bacteriological spectrum in the different Wagner's grades of foot wounds . Most of the diabetic foot wounds were found to be polymicrobic in nature with an average of 3.07 organisms isolated per case studied . Amongst a total of 775 clinical isolates, 71.09% were aerobic; whereas 28.91% were anaerobic pathogens . Gram-positive organisms like Staphylococcus spp . and Streptococcus spp . formed almost 50% of the clinical isolates in the first two grades and were reduced to less one-fourth of the total organisms in the last two grades . These was a significant increase in the gram-negative organisms and anaerobes in the last two grades. Emerg Infect Dis, 1998 Oct-Dec, 4(4), 645 - 7 Streptococcus parasanguinis: new pathogen associated with asymptomatic mastitis in sheep; Fernandez-Garayzabal JF et al.; We describe two unusual cases in sheep of subclinical mastitis caused by Streptococcus parasanguinis . This bacterium has been associated with the development of experimental endocarditis; its presence at relatively high concentrations in apparently healthy sheep milk may pose a health risk in persons with predisposing heart lesions. West J Med, 1998 Dec, 169(6), 364 - 9 Prevalence of antimicrobial drug-resistant Streptococcus pneumoniae in Washington State; Frick PA et al.; We conducted a survey to assess the prevalence and geographic distribution of antimicrobial drug resistance among invasive isolates of Streptococcus pneumoniae in Washington State . Sequential sterile-site pneumococcal isolates were submitted from 13 hospital laboratories between 1 October 1995 and 30 January 1997 . We serotyped 275 isolates from adults and children and determined minimum inhibitory concentrations (MIC) for commonly used antimicrobial drugs . Data were abstracted from medical records to compare differences in outcome and risk factors for infection . Of the 275 isolates, 73 (26.5%) were nonsusceptible to one or more antimicrobial drugs . Penicillin-nonsusceptible pneumococci (PNSP, MIC > or = 0.1 microgram/ml) accounted for 42 (15.3%) of the 275 isolates including 4 (1.5%) resistant strains (MIC > or = 2 micrograms/ml) . The 42 PNSP included serogroups 6, 9, 14, 19, and 23, all of which are represented in the 23-valent pneumococcal vaccine . PNSP were also nonsusceptible to trimethoprim/sulfamethoxazole (92.9%), erythromycin (38.1%), imipenem (28.6%), and ceftriaxone (23.8%) . Forty-seven (17.1%) of the 275 isolates were multiple drug-nonsusceptible pneumococci (MDNSP) . A significantly greater number of patients < or = 12 years of age were infected with MDNSP compared with those > 12 years . Prior use of antimicrobial drugs and an immunosuppressive disorder were risk factors for infection with PNSP . In summary, pneumococci nonsusceptible to penicillin and other antimicrobial drugs are prevalent among adults with invasive pneumococcal disease in Washington State . A large proportion of PNSP are resistant to other commonly used antimicrobial drugs . Local antibiotic susceptibility data should be considered when designing empiric treatment regimens. Arch Surg, 1998 Dec, 133(12), 1362 - 5 Postsplenectomy Capnocytophaga canimorsus sepsis presenting as an acute abdomen; Sawmiller CJ et al.; Patients with intra-abdominal processes that require prompt surgical intervention, including appendicitis, perforated viscus, ischemic bowel, volvulus, and bowel obstruction, often present with signs and symptoms of an acute abdomen . Several medical problems can mimic an acute abdomen . Overwhelming postsplenectomy infection is a life-threatening condition that can present with acute abdominal symptoms . The incidence of overwhelming postsplenectomy infection ranges from 1% to 25%, and is caused by Streptococcus pneumoniae in 50% of cases . Capnocytophaga canimorsus, a bacteria commonly found in dog saliva, accounts for less than 1% of cases . Overwhelming postsplenectomy infection has a rapidly deteriorating course that progresses to respiratory and renal failure, cardiovascular collapse, and death . The mortality associated with overwhelming postsplenectomy infection is 60% to 80% . Early diagnosis and institution of appropriate antibiotic therapy and supportive care is essential to improve patient outcome . A previously healthy woman who had undergone splenectomy secondary to trauma 11 years earlier presented with symptoms of an acute abdomen . A diagnosis of overwhelming postsplenectomy infection due to C canimorsus was made based on her peripheral blood smear and blood culture findings . Early aggressive care and antibiotic treatment resulted in a successful outcome for this patient with no long-term morbidity . This patient's clinical course demonstrates the importance of early diagnosis and treatment of overwhelming postsplenectomy infection. J Cardiol, 1998 Nov, 32(5), 331 - 6 {Aortic valvular vegetation in annuloaortic ectasia due to idiopathic cystic medial necrosis: a case report}; Fujiyama A et al.; Annuloaortic ectasia is often accompanied by Marfan syndrome and associated with infective endocarditis usually involving the mitral valves . We treated a patient with annuloaortic ectasia due to idiopathic cystic medial necrosis who developed congestive heart failure with aortic valvular vegetation . A 56-year-old man had dyspnea on effort since the beginning of January, 1997 and was admitted to our hospital on April 6, 1997 because of orthopnea . The diagnosis was congestive heart failure due to severe aortic regurgitation with annuloaortic ectasia detected by echocardiography . Medication and rest after hospitalization relieved his symptoms but congestive heart failure deteriorated after he had a high fever . At this time, a vegetation attached to the noncoronary cusp of the aortic valve was found which had not been detected on admission . Blood culture yielded Streptococcus sanguis . The diagnosis was infective endocarditis involving the aortic valve . Surgical correction (Bentall method) improved congestive heart failure and he was discharged on August 4, 1997 without recurrence of endocarditis . Infective endocarditis involving the aortic valves is a possible cause of development or deterioration of congestive heart failure in patients with annuloaortic ectasia. J Bacteriol, 1999 Jan, 181(1), 63 - 7 Construction and analysis of a Streptococcus parasanguis recA mutant: homologous recombination is not required for adhesion in an in vitro tooth surface model; Froeliger EH et al.; PCR was used to amplify an internal region of the recA gene from Streptococcus parasanguis FW213 . The PCR fragment was used as a probe to recover the entire streptococcal recA gene from an S . parasanguis genomic library, and the sequence of the gene was determined . The deduced product of the S . parasanguis recA gene showed a high degree of amino acid identity with other prokaryotic RecA proteins . The cloned recA sequence was disrupted in vitro by insertional mutagenesis, and the mutated allele was then introduced into the S . parasanguis chromosome by homologous recombination . Results of Southern hybridizations confirmed the replacement of the wild-type recA gene with the mutated allele . The recA mutant strain was considerably more sensitive to UV light than the parental strain, and this phenotype was consistent with a mutation in recA . The S . parasanguis recA mutant showed no reduction in its ability to adhere in the in vitro tooth surface model, saliva-coated hydroxylapatite (SHA), or in its ability to express the fimbria-associated adhesin Fap1 . These results demonstrate that in vitro attachment of S . parasanguis FW213 to SHA and expression of Fap1 are recA independent. Infect Immun, 1999 Jan, 67(1), 426 - 8 Tonsillar application of formalin-killed cells of Streptococcus sobrinus reduces experimental dental caries in rabbits; Fukuizumi T et al.; Living Streptococcus sobrinus cells were orally inoculated into nonimmune rabbits and rabbits immunized with formalin-killed cells of S . sobrinus through tonsillar application to examine the anticaries potential of this method of immunization . The living S . sobrinus cell numbers and the caries areas in the rabbits immunized by tonsillar application decreased to a level one-fifth of that in nonimmune rabbits. Infect Immun, 1999 Jan, 67(1), 413 - 6 Five homologous repeats of the protein G-related protein MIG cooperate in binding to goat immunoglobulin G; Vasi J et al.; Protein MIG, from Streptococcus dysgalactiae, binds alpha2-macroglobulin and immunoglobulin G (IgG) . MIG-derived fusion proteins with one to five IgG-binding repeats differed up to 72,000- fold in avidity for goat IgG, indicating a considerable cooperativity of the repeats . Significant sequence variation in the IgG-binding repeats was recognized . Protein MIG interacted with goat IgG1 via both the Fc and Fab parts. Infect Immun, 1999 Jan, 67(1), 126 - 30 Streptococcal pyrogenic exotoxin B induces apoptosis and reduces phagocytic activity in U937 cells; Kuo CF et al.; Treatment of U937 human monocyte-like cells with Streptococcus pyogenes led to an induction of apoptosis in these cells . A comparison between the wild-type strain and its isogenic protease-negative mutant indicated that the production of streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease, caused a greater extent of apoptosis in U937 cells . Further study using purified SPE B showed that this protease alone could induce U937 cells to undergo apoptosis, which was characterized by morphologic changes, DNA fragmentation laddering on the gel, and an increase in the percentages of hypodiploid cells . The protease activity of SPE B was required for apoptosis to proceed, since treatment with cysteine protease inhibitor E64 or heat inactivation abrogated this death-inducing effect . The SPE B-induced apoptosis pathway was interleukin-1beta converting enzyme (ICE) family protease dependent . Further experiments showed that the phagocytic activity of U937 cells was reduced by SPE B . Treatment with E64 and heat inactivation both abrogated this phagocytosis-inhibitory effect . Taken together, the present data show that SPE B not only possesses the ability to induce apoptosis in monocytic cells but also helps bacteria to resist phagocytosis by host cells. J Pharm Biomed Anal, 1998 Oct, 18(1-2), 219 - 25 Isolation of an antibacterial component from roasted coffee; Daglia M et al.; A coffee beverage obtained from instant dark coffee that had been previously shown to possess high antibacterial activity, was acidified (pH 2) and extracted with ethyl acetate . After alkalinization (pH 12) the aqueous phase was re-extracted with the organic solvent . The acidic and basic extracts were evaporated to dryness and the aqueous phase freeze-dried . Residues were dissolved in sterile water and assayed for antibacterial activity against two reference bacteria (Staphylococcus aureus ATCC 25923 and Streptococcus mutans 9102) . The acidic extract was found to be highly active and was separated by gel permeation chromatography (GPC) into five fractions . Fractions GPC4 and GPC5 were found to possess antibacterial activity: most of the activity was evident in fraction GPC5 . These fractions were separated by RP-HPLC using a gradient elution with methanol water as mobile phase . Both GPC fractions gave an active subfraction with methanol-water (70:30, v/v) . The experimental conditions used to separate the antibacterial compound that originates during the roasting process, indicate that it possesses low molecular mass (probably no more than 200 Da), weak acidic properties and an lambda(max) at 205 nm . The very small amount of this compound isolated from roasted coffee, indicates that it may be a very strong antibacterial agent. Structure, 1998 Dec 15, 6(12), 1563 - 75 Crystal structure of the DpnM DNA adenine methyltransferase from the DpnII restriction system of streptococcus pneumoniae bound to S-adenosylmethionine; Tran PH et al.; Background: . Methyltransferases (Mtases) catalyze the transfer of methyl groups from S-adenosylmethionine (AdoMet) to a variety of small molecular and macromolecular substrates . These enzymes contain a characteristic alpha/beta structural fold . Four groups of DNA Mtases have been defined and representative structures have been determined for three groups . DpnM is a DNA Mtase that acts on adenine N6 in the sequence GATC; the enzyme represents group alpha DNA Mtases, for which no structures are known . Results: . The structure of DpnM in complex with AdoMet was determined at 1.80 A resolution . The protein comprises a consensus Mtase fold with a helical cluster insert . DpnM binds AdoMet in a similar manner to most other Mtases and the enzyme contains a hollow that can accommodate DNA . The helical cluster supports a shelf within the hollow that may recognize the target sequence . Modeling studies indicate a potential site for binding the target adenine, everted from the DNA helix . Comparison of the DpnM structure and sequences of group alpha DNA Mtases indicates that the group is a genetically related family . Structural comparisons show DpnM to be most similar to a small-molecule Mtase and then to macromolecular Mtases, although several dehydrogenases show greater similarity than one DNA Mtase . Conclusions: . DpnM, and by extension the DpnM family or group alpha Mtases, contains the consensus fold and AdoMet-binding motifs found in most Mtases . Structural considerations suggest that macromolecular Mtases evolved from small-molecule Mtases, with different groups of DNA Mtases evolving independently . Mtases may have evolved from dehydrogenases . Comparison of these enzymes indicates that in protein evolution, the structural fold is most highly conserved, then function and lastly sequence. Structure, 1998 Dec 15, 6(12), 1553 - 61 The crystal structure of pneumococcal surface antigen PsaA reveals a metal-binding site and a novel structure for a putative ABC-type binding protein; Lawrence MC et al.; Background: . The surface protein PsaA of the pathogenic bacterium Streptococcus pneumoniae plays an essential role in its virulence . PsaA is a putative ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of Mn2+ and possibly Zn2+ and is considered to be both a potential drug target and and a candidate vaccine component . Results: . The structure of PsaA has been determined to 2.0 A resolution using X-ray crystallography and is the first structure obtained for an ABC-type binding protein from a Gram-positive organism . The protein consists of two (beta/alpha)4 domains linked together by a single helix . A metal-binding site is formed in the domain interface by the sidechains of His67, His139, Glu205 and Asp280 and is occupied in the structure . Conclusions: . The structural topology of PsaA is fundamentally different from that of other ABC-type binding proteins determined thus far in that PsaA lacks the characteristic 'hinge peptides' involved in conformational change upon solute uptake and release . In our structure, the metal-binding site is probably occupied by Zn2+ . The site seems to be well conserved amongst related receptors from both Gram-positive and Gram-negative bacteria. Arch Phys Med Rehabil, 1998 Dec, 79(12), 1504 - 9 Immunogenicity of pneumococcal vaccine in persons with spinal cord injury; Waites KB et al.; OBJECTIVE: To determine immunogenicity and optimum timing for administering the 23-valent pneumococcal vaccine after spinal cord injury (SCI) . DESIGN: Double-blind, randomized, placebo control study . SETTING: SCI unit in a tertiary care medical center and community . PARTICIPANTS: Eighty-seven persons with recent SCI . INTERVENTION: Participants were randomized to receive either placebo or pneumococcal vaccine at 16 to 18 days versus 4 to 6 months postinjury . MAIN OUTCOME MEASURES: Antibody concentrations were measured prior to intervention and 1, 2, and 12 months afterward to evaluate the immune response to five serotypes of Streptococcus pneumoniae . Effects of demographic and injury-related variables on immune response were also evaluated . RESULTS: Timing of vaccination did not influence mean antibody concentrations for any serotype (p > .05) . Ninety-five percent of vaccinated persons had twofold or greater increases in antibody concentration for at least one serotype when measured 1 month after vaccination versus 35% of placebo groups (p < .01) . After 12 months, 93% of vaccinated persons in both groups maintained antibody concentrations twofold or greater than baseline values . CONCLUSIONS: Most participants developed an immune response to at least one serotype that was maintained for at least 12 months . Immune response varied according to serotype . Given the favorable immune response and no effect of timing, persons with SCI should receive pneumococcal vaccine during initial hospitalization. Zentralbl Bakteriol, 1998 Nov, 288(3), 421 - 8 Rate of carriage, serotype distribution and penicillin resistance of Streptococcus pneumoniae in healthy children; Sener B et al.; This study was aimed to define the carriage rates for Streptococcus pneumoniae in a given population in Ankara and also to determine the serotypes and penicillin resistance of these strains . Oropharyngeal swabs were taken from a total of 661 children aged between 0-11 years and living in a province of Ankara between January 1995-January 1997 . Serotyping was performed by detection of the Quellung reaction . The isolates were screened for penicillin susceptibility by the agar dilution method according to the guidelines of NCCLS . The total rate of pneumococcal carriage in the study population was 23.90% and the isolation rate was found to be statistically associated with age, being higher in small children . Among the 158 S . pneumoniae isolates, the most prevalent serotypes (in order of frequency) were 6, 19, 9, 23, 3 and 14 . Penicillin susceptibility was examined in 120 of the isolates . 55 of them (45.83%) were susceptible, 53 (44.17%) were intermediately and 12 (10.0%) were highly resistant to penicillin . Evaluation of the results showed that serotypes 6, 14 and 23 were those most often associated with penicillin resistance . The significant rate of isolation of penicillin-resistant pneumococci in healthy carriers points to the importance of active immunization in risk groups and also the importance of the rational use of antibiotics to limit the spread of resistant strains. Arch Dermatol Res, 1998 Nov, 290(11), 628 - 33 Effects of diclofenac on experimental streptococcal necrotizing fasciitis (NF) in rabbit; Guibal F et al.; Aggravation of necrotizing fasciitis (NF) by the administration of non-steroidal antiinflammatory drugs (NSAIDs) has recently been suggested . A rabbit model of streptococcal NF was used to study the effects of parenteral administration of an NSAID on NF evolution and outcome . Of 16 rabbits inoculated with a Streptococcus pyogenes suspension together with staphylococcal alpha toxin, 8 were treated with two doses of 4 mg/kg diclofenac on day 1 after inoculation . Clinical, bacteriological and histological studies were performed until day 10 . Under our experimental conditions, NSAID treatment significantly limited NF extension . A specific inverse relationship between the extent of inflammation and bacterial density in NF lesions was observed on day 1 after inoculation in the treated group suggesting that the greater severity of NF in humans treated with an NSAID could be due to the therapeutic delay induced by the misleading clinical effects of the NSAID, and not to inhibition of antibacterial defence. Allergy, 1998 Nov, 53(11), 1101 - 3 Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome; Kojima K et al.; We report a case of hyperimmunoglobulin E syndrome (HIE) complicated by neutrophil deficiency which was successfully treated with oral administration of disodium cromoglycate . A 48-year-old Japanese man with HIE developed Streptococcus pneumoniae meningitis . Laboratory tests after the meningitis revealed persistent neutropenia (300-800/mm3) and defects of phagocytosis and bacterial killing by neutrophils . Administration of disodium cromoglycate was started, and neutrophil counts gradually increased to 1200-1600/mm3 . The impaired neutrophil activities returned to normal . The patient improved clinically; during the 2-year treatment, he had only two brief episodes of the common cold . Disodium cromoglycate may have potential clinical use in the treatment of cases of HIE even with neutrophil deficiency. Acta Odontol Scand, 1998 Oct, 56(5), 293 - 8 Comparison of dentin apposition and dentinal caries progression in the mandibular and maxillary molars of the rat; Pekkala E et al.; To show that the rate and the rate of reduction of dentin apposition are about the same in mandibular and maxillary molars, 23 Sprague-Dawley rat pups were randomized into 2 groups on the day of birth . During lactation half of their dams received a standard rodent diet; the other half, a diet containing 41% sucrose . At the age of 3 weeks the pups were weaned, weighed, given an intraperitoneal injection of oxytetracycline hydrochloride, and inoculated with oral Streptococcus sobrinus . During the experiment the pups received the same diet as their dams during lactation . After 5 weeks the pups were decapitated, their jaws sectioned sagittally, the first and second molars photographed, and the areas of dentin apposition and dentinal caries measured planimetrically . The area of dentin formation was about the same in maxilla and mandible in the first molars, but slightly smaller in the mandibular second molars of the control group . The sucrose diet reduced dentin apposition significantly in both jaws, although the areas were significantly smaller in the mandibles than in the maxillae . Caries did not affect the rate of dentin apposition . The areas of caries lesions were smaller in the maxillary molars of both diet groups . The results show that the hypothesis of equal rate of dentin apposition in mandible and maxilla was not valid because the reduction, caused by sucrose, was more prominent in mandibular molars for unknown reasons . The reduction of dentin apposition was reflected as acceleration of caries progression among the diet groups and the jaws . It was concluded that the response of the pulpodentinal complex to sucrose and dentinal caries during the primary dentinogenesis cannot be seen as a formation of reactionary or reparative dentin, as with adult rats. Acta Odontol Scand, 1998 Oct, 56(5), 276 - 80 Effects of continuous glucocorticoid infusion on the progression of dentinal caries in growing rats; Huumonen S et al.; This study was undertaken to test the effects of a low dose of continuous glucocorticoid infusion on the rate of progression of dentinal caries in molars of young rats . Forty-seven rats were inoculated in the mouth with Streptococcus sobrinus and fed ad libitum a cariogenic diet and 10% sweetened water . After 10 days of caries initiation ten animals were killed to serve as a reference group . In the rest of the animals the cortisone or placebo pellet was implanted subcutaneously in the back of the neck . The daily release of cortisone was 0.42 mg per rat . Sweetened water was changed to pure water, and the diet was the same cariogenic diet . After 6 weeks of medication the areas of dentinal caries were quantified planimetrically . Schiff's staining was used to classify caries . Although cortisone medication slightly increased the number of carious lesions, statistical significance was not reached . However, compared with the placebo group, the rats receiving cortisone medication showed significantly increased dentinal caries progression and severity of lesions . This study suggests that glucocorticoids with a cariogenic diet reduce the intrinsic modulation or response of the odontoblasts to caries attack. J Acquir Immune Defic Syndr Hum Retrovirol, 1998 Dec 15, 19(5), 471 - 7 Time course of antibody response to tetanus toxoid and pneumococcal capsular polysaccharides in patients infected with HIV; Talesnik E et al.; The temporal course of the humoral immune response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients . In all, 26 seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination . For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization . Overall only 6 patients (23%) showed a significant response . At 12 months postvaccination, Ttox-IgG and T-tox-IgG1 were significantly lower than baseline levels (Ttox IgG basal; 11.0 mg/L, 12 months; 0.8 mg/L, Ttox IgG1 baseline; 13.1 mg/L, Ttox IgG1 12 months; 2.4 mg/L) and in 10 patients, antibodies that fell below protective levels (0.6 mg/L) . In contrast with PPS, a significant response was observed at 2 and 12 months (PPS-IgG basal; 35.9 U/ml, 2 months; 151.4 U/ml, 12 months; 59.7 U/ml; PPS-IgG2 baseline 20.3 U/ml, 2 months; 113.2 U/ml, 12 months; 51.9 U/ml) . Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharides antigens . Immunization with the Ttox T-cell-dependent antigen fails to elicit a significant immune response and may induce inhibition of antibody production in HIV-infected patients . In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patientsPIP: The temporal course of the humoral response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients . 26 HIV-seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination . For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization . Overall, 6 patients (23%) showed a significant response . At 12 months postvaccination, Ttox-IgG and Ttox-IgG1 were significantly lower than baseline levels, and in 10 patients, antibodies fell below protective levels . In contrast with PPS, a significant response was observed at 2 and 12 months . Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharide antigens . Immunization with the Ttox T-cell-dependent antigen elicits no significant immune response and may induce inhibition of antibody production in HIV-infected patients . In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patients . Dis Mon, 1998 Nov, 44(11), 613 - 75 Community-acquired pneumonia; Cassiere HA et al.; Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality in all age groups, especially the elderly, which is a patient population that continues to grow . Recently the spectrum and clinical picture of pneumonia has been changing as a reflection of this aging population; this requires a reassessment of and a new approach to the patient with pneumonia . Currently, pneumonia patients are classified as having either community-acquired or hospital-acquired infection rather than typical versus atypical . Patients who have CAP are categorized by age, presence of a coexisting medical illness, and the severity of the pneumonia . The rationale behind categorizing patients is to stratify them in terms of mortality risk to help determine the location of therapy (e.g., outpatient, inpatient, intensive care unit) and focus the choice of initial antimicrobial therapy . Once the decision to hospitalize a patient with pneumonia is made, the next step is to decide on an appropriate diagnostic evaluation and antibiotic therapy . Both decisions have evolved over the last several years since the publication of the American Thoracic Society's CAP guidelines . The current approach to the diagnostic work-up of pneumonia stresses a limited role of diagnostic tests and procedures . The antimicrobial regimen has now evolved into one that is empiric in nature and based on the age of the patient, the presence of coexisting medical disease, and the overall severity of the pneumonia . This process is a dynamic once because bacterial resistance to commonly used antibiotics can further complicate the course of pneumonia therapy, but the impact of resistance on outcome is less clear . Resistance of Streptococcus pneumoniae to penicillin is a prime example of this growing problem, and adjustment to pneumonia therapy may be required . A difficult but not uncommon problem in pneumonia patients is slow recovery and delayed resolution of radiographic infiltrates . Factors that impact negatively on pneumonia resolution include advanced age and the presence of serious comorbid illnesses such as diabetes mellitus, renal disease, or chronic obstructive pulmonary disease . In addition, certain organism factors (e.g., intrinsic virulence) may interact with host factors and advanced age to delay pneumonia resolution . For example, 50% of patients with pneumococcal pneumonia have radiographic clearing at 5 weeks, and the majority clear within 2 to 3 months . Recent data demonstrate that radiographic resolution of CAP is most influenced by the number of lobes involved and the age of the patient . Radiographic clearance of CAP decreases by 20% per decade after age 20, and patients with multilobar infiltrates take longer to clear than those with unilobar disease . In general, when approaching slowly resolving infiltrates after pneumonia, bronchoscopic evaluation and lung biopsy are more likely to yield a specific diagnosis if the patient is a nonsmoker younger than 55 years old with multilobar disease . If the patients has either no identifiable factors associated with prolonged pneumonia resolution or the repeat chest radiograph at 1 month shows no appreciable change, further diagnostic testing is indicated . The route and duration of antibiotic therapy, another detail of the management of CAP patients that has changed recently, is complicated by the fact that the majority of patients with CAP have no pathogen identified . Therefore, in most instances the physician initiates empiric antibiotics on the basis of epidemiologic data . If an etiologic pathogen is identified (either initially or at a later time), then the antibiotic spectrum can be narrowed . When no pathogen is discovered, broad-spectrum empiric antibiotics are continued . (ABSTRACT TRUNCATED) Med Dosw Mikrobiol, 1998, 50(1-2), 105 - 13 {Distribution of IgG subclasses and their biological activity in bioglobulin}; Bucholc B et al.; Preparations of human immunoglobulin for intravenous use (IVIG) should contain proper percentage of IgG subclasses, corresponding to physiological proportions with preserved activity of antibodies . The amounts of IgG subclasses were determined using the radial immunodiffusion technique against to the WHO reference serum 67/97 . It appears that variations are observed among the different lots and manufacturers of the various formulations of IVIG available in Poland . Although some of these differences are not statistically significant, significant differences in subclass concentrations were found between formulation of IVIG, with Bioglobulina being lower in IgG1 and higher in IgG2 and Endobulin having a lower per cent of IgG3 . The study was aimed at establishment of activity values against diphtheria and tetanus toxoids and Streptococcus group B (GBS) . IgG antibodies to tetanus and diphtheria toxoid antigens were predominantly of the IgG1 and IgG2 isotype . IgG4 subclass, was present in smaller proportion and IgG3 fractions was absent . Antibodies to GBS were only IgG2 and IgG1 isotypes . Basing on obtained results it can be stated that in spite of the imbalance between the amounts of IgG1 and IgG2 in Bioglobulina, the activity which was determined in subclasses is comparable with that of other IVIGs. Neurosci Lett, 1998 Nov 13, 256(3), 127 - 30 Experimental pneumococcal meningitis in rabbits: the increase of matrix metalloproteinase-9 in cerebrospinal fluid correlates with leucocyte invasion; Azeh I et al.; Gelatinolytic activity of matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-2, was studied by quantitative zymography in a rabbit model of bacterial meningitis during 24 h after inoculation with Streptococcus pneumoniae . In cerebrospinal fluid (CSF), MMP-2 was constitutively present and its level did not change during the experiment . In contrast, MMP-9, hardly detectable in CSF of healthy animals, increased dramatically . The increase of MMP-9 was correlated with both, an increase of CSF cell count and of total protein concentration . Intrathecal production of MMP-9 and MMP-2 was demonstrated by zymography of equal amounts of total protein from CSF and serum . Homogenates, prepared from various cortical regions of infected rabbits did not show increase of MMP activities . On the other hand, leucocytes isolated from CSF expressed high levels of MMP-9 suggesting a significant contribution of these cells to the elevation of MMP-9 activity in this body fluid. Eur J Gastroenterol Hepatol, 1998 Apr, 10(4), 353 - 4 Fatal pneumococcal septicaemia in a coeliac patient; Johnston SD et al.; A 78-year-old lady initially presented with painful hips, low back pain, lethargy and weight loss . She had a past history of osteomalacia . Investigations revealed evidence of malabsorption and jejunal biopsy revealed sub-total villous atrophy in keeping with coeliac disease . Peripheral blood film was within normal limits . She responded well clinically to a gluten-free diet and calcium and vitamin D supplementation . Four years after the initial diagnosis she presented acutely with vomiting, pleuritic chest pain, pyrexia and bronchospasm . Blood cultures confirmed the presence of Streptococcus pneumoniae and she was treated appropriately with ampicillin . Despite this she died shortly after admission . It is recognized that blood film examination alone cannot exclude hyposplenism complicating coeliac disease and it is presumed that this was the reason for the development of fatal pneumococcal septicaemia in this patient . Prophylactic vaccination may be appropriate in hyposplenism secondary to coeliac disease. J Clin Microbiol, 1999 Jan, 37(1), 263 - 5 Serotyping of Streptococcus pneumoniae by coagglutination with 12 pooled antisera; Lalitha MK et al.; We report on the performance of a recently introduced commercial chessboard method using 12 antisera, in comparison with that of the 55-antiserum panel used in determining the serogroups and types (SGTs) of Streptococcus pneumoniae, both of which were carried out by a coagglutination technique . Of a total of 150 strains of S . pneumoniae studied, 135 (90%) belonged to the SGTs represented in the 23-valent pneumococcal vaccine; of these, 130 (96.3%) were identified as the same SGTs by both typing methods . The remaining five strains showed cross-reactivity with more than two pools by the chessboard method, but could be assigned to a single SGT by the Quellung test . The 96.3% concordance of the chessboard method suggests it can be adopted for determination of the SGTs of S . pneumoniae in laboratories. J Clin Microbiol, 1999 Jan, 37(1), 221 - 4 Dissemination of high-level penicillin-, extended-spectrum cephalosporin-, and erythromycin-resistant Streptococcus pneumoniae clones in Taiwan; Hsueh PR et al.; Sixty-seven clinical isolates of Streptococcus pneumoniae (40 of serotype 23F, 19 of serotype 19F, and 8 of serotype 6B) with decreased susceptibilities to penicillin and erythromycin were characterized by antimicrobial susceptibility patterns; DNA restriction endonuclease cleavage profiles of the penicillin-binding protein genes pbp1a, pbp2b, and pbp2x; random amplified polymorphic DNA (RAPD) patterns generated by arbitrarily primed PCR; and chromosomal macrorestriction profiles based on pulsed-field gel electrophoresis . A total of 22 clones (identical or closely related pulsotypes and identical RAPD patterns) were identified; 14 clones of 23F, 6 of 19F, and 2 of 6B . Three 23F clones (26 isolates) and one 19F clone (9 isolates) expressed high-level resistance to penicillin, cefotaxime, and erythromycin (MICs >/= 256 microg/ml) . These data strongly suggest that multiple high-level penicillin-, extended-spectrum cephalosporin-, and macrolide-resistant clones of S . pneumoniae have been disseminated in Taiwan. J Clin Microbiol, 1999 Jan, 37(1), 215 - 7 Determination of trimethoprim-sulfamethoxazole resistance in Streptococcus pneumoniae by using the E test with Mueller-Hinton agar supplemented with sheep or horse blood may be unreliable . The Pneumococcal Study Group; Lovgren M et al.; An international, multicenter study compared trimethoprim-sulfamethoxazole MICs for 743 Streptococcus pneumoniae isolates (107 to 244 isolates per country) by E test, using Mueller-Hinton agar supplemented with 5% defibrinated horse blood or 5% defibrinated sheep blood, with MICs determined by the National Committee for Clinical Laboratory Standards broth microdilution reference method . Agreement within 1 log2 dilution and minor error rates were 69.3 and 15.5%, respectively, on sheep blood-supplemented agar and 76.9 and 13.6%, respectively, with horse blood as the supplement . Significant interlaboratory variability was observed . E test may not be a reliable method for determining the resistance of pneumococci to trimethoprim-sulfamethoxazole. J Clin Microbiol, 1999 Jan, 37(1), 157 - 60 Detection of penicillin susceptibility in Streptococcus pneumoniae by pbp2b PCR-restriction fragment length polymorphism analysis; O'Neill AM et al.; A PCR-restriction fragment length polymorphism strategy directed against the pbp2b gene was evaluated for identification of penicillin susceptibility . A total of 106 United Kingdom (U.K.), 30 Danish, and 11 Papua New Guinean strains were tested . Of the U.K . strains, all the susceptible and all but one of the resistant isolates were correctly assigned . By using conventional definitions of "not resistant" and "not susceptible," the sensitivities were 97 . 5 and 94.4%, the specificities were 100 and 98.9%, the positive predictive values were 100 and 94.4%, and the negative predictive values were 93.1 and 98.9%, respectively . This technique may allow susceptible (MIC, <0.1 mg/liter) and resistant (MIC, >1 mg/liter) isolates to be distinguished in a single PCR. Gastrointest Endosc, 1998 Dec, 48(6), 568 - 73 Viridans streptococcal bacteremia after esophageal stricture dilation; Zuccaro G Jr et al.; BACKGROUND: The incidence of bacteremia with organisms that may cause infective endocarditis after esophageal stricture dilation is unknown . There is disagreement among physicians regarding the need for antibiotic prophylaxis for patients with valvular heart disease undergoing dilation . Our aim was to determine the frequency and duration of bacteremia associated with esophageal stricture dilation . METHODS: Blood cultures were obtained before and after stricture dilation in patients without valvular heart disease and in a control group of patients undergoing upper endoscopy without dilation . RESULTS: A total of 103 patients undergoing dilation and 50 control patients were studied; 22 of 103 patients (21%) undergoing dilation had at least one post-procedure blood culture positive for viridans streptococcus, compared with 1 of 50 (2%) of control patients (p = 0 . 001) . Blood cultures obtained 1 minute after stricture dilation were positive for viridans streptococcus in 19 of 81 (23%), in 16 of 96 (17%) 5 minutes post-dilation, and in 3 of 63 (5%) 20 to 30 minutes post-dilation . Of the 19 patients with viridans streptococcus bacteremia 1 minute after dilation, cultures were still positive in 14 of 19 (74%) at 5 minutes and in 2 of 19 (10%) 20 to 30 minutes post-dilation . CONCLUSIONS: These data support the use of antibiotic prophylaxis before esophageal stricture dilation for patients with valvular heart disease at risk for the development of infective endocarditis. Am J Respir Crit Care Med, 1998 Dec, 158(6), 1839 - 47 Epidemiology of ventilator-acquired pneumonia based on protected bronchoscopic sampling; George DL et al.; We performed a prospective observational cohort study of the epidemiology and etiology of nosocomial pneumonia in 358 medical ICU patients in two university-affiliated hospitals . Protected bronchoscopic techniques (protected specimen brush and bronchoalveolar lavage) were used for diagnosis to minimize misclassification . Risk factors for ventilator-associated pneumonia were identified using multiple logistic regression analysis . Twenty-eight cases of pneumonia occurred in 358 patients for a cumulative incidence of 7.8% and incidence rates of 12.5 cases per 1, 000 patient days and 20.5 cases per 1,000 ventilator days . Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Hemophilus species made up 65% of isolates from the lower respiratory tract, whereas only 12.5% of isolates were enteric gram-negative bacilli . Daily surveillance cultures of the nares, oropharynx, trachea, and stomach demonstrated that tracheal colonization preceded ventilator-associated pneumonia in 93.5%, whereas gastric colonization preceded tracheal colonization for only four of 31 (13%) eventual pathogens . By multiple logistic regression, independent risk factors for ventilator- associated pneumonia were admission serum albumin <= 2.2 g/dl (odds ratio {OR} 5.9; 95% confidence interval {CI} 2.0-17.6; p = 0.0013), maximum positive end-expiratory pressure >= 7.5 cm H2O (OR, 4.6; 95% CI, 1.4 to 15.1; p = 0.012), absence of antibiotic therapy (OR, 6.7; 95% CI, 1.8 to 25.3; p = 0.0054), colonization of the upper respiratory tract by respiratory gram-negative bacilli (OR, 3.4; 95% CI, 1.1 to 10.1; p = 0.028), pack-years of smoking (OR, 2.3 for 50 pack-years; 95% CI, 1 . 2 to 4.2; p = 0.012), and duration of mechanical ventilation (OR, 3 . 4 for 14 d; 95% CI, 1.5 to 7.8; p = 0.0044) . Several of these risk factors for ventilator-associated pneumonia appear amenable to intervention. South Med J, 1998 Dec, 91(12), 1167 - 8 Streptococcus bovis bacteremia: unusual complications; Genta PR et al.; Streptococcus bovis bacteremia is known to be related to neoplastic lesions of the colon . We describe a patient with several complications of S bovis bacteremia and adenocarcinoma of the colon--endocarditis, spondylodiskitis, and splenic abscess . We believe this is the eighth known case of endocarditis and diskitis caused by S bovis and the third case of endocarditis and splenic abscess by S bovis in a patient with adenocarcinoma of the colon. Auris Nasus Larynx, 1998 Dec, 25(4), 403 - 6 Retropharyngeal abscess: recent trends; Sharma HS et al.; Retropharyngeal abscess (RPA) is relatively rare today . A study of 17 cases of RPA treated at our hospital in the past 10 years showed a shift in the disease from children below 6 years of age (41%) to older children and adults (58%) . Upper respiratory tract infection (URTI) was found to be the commonest (52%) aetiological predisposing factor in all age groups . Other aetiological factors were septicaemia (11%) in children below the age of 6 years and trauma due to foreign body (35%) in the older children and adult age groups . Klebsiella, Staphylococcus and Streptococcus were the commonest species of microorganisms grown from pus . The changing clinical trends, microbiology, choice of antibiotics, usefulness of radiology, and complications of this potentially fatal illness are discussed. Ann Med Interne (Paris), 1998 Oct, 149(6), 323 - 5 {Resistance to penicillin G and Streptococcus pneumoniae infection at the Hôpital Foch, Paris, France, in 1995}; Mouly S et al.; Decreased susceptibility to penicillin G of pneumococcal strains is continuously increasing in France . OBJECTIVE: We assessed effect of resistance to penicillin on therapeutic management and mortality in adults with pneumococcal pneumonia in our hospital . METHODS: This one-year retrospective study (1995) included patients with proven pneumococcal infection (positive blood culture, pleural fluid, or specimens from the lower respiratory tract) . Strains of Streptococcus pneumoniae were screened for susceptibility to antimicrobial agents . Resistance to penicillin G was defined as a minimal inhibitory concentration > or = 0.12 microgram/ml . Age immune and nosocomial status, first and second line antibiotherapy and death were compared according to the strains susceptibility to penicillin G . A p value below 0.05 was statistically significant . RESULTS: In 15 cases a pneumococcal strain susceptible to penicillin G was isolated while 23 patients were infected with a strain with a decreased susceptibility to penicillin G . Age was significantly higher in the latest group (61.6 versus 54.7 years) while no difference was noted between the 2 groups according to immune and nosocomial status, therapeutic management and death . DISCUSSION: Resistance to penicillin did neither appear to increase mortality nor to influence therapeutic management in patients with pneumococcal infection. Zentralbl Veterinarmed B, 1998 Nov, 45(9), 539 - 49 Decreased growth of Streptococcus uberis in milk from mammary glands of cows challenged with the same mastitis pathogen; Fang W et al.; Milk samples from mammary glands challenged with Streptococcus uberis and from unchallenged mammary glands were selected for analyses of bacterial growth, antibody response, and lactoperoxidase activity . All challenged mammary glands became infected with isolation of S . uberis and elevated somatic cell counts in milk during the first week after challenge . In vitro growth of the homologous challenge strain and a heterologous strain of S . uberis was significantly lower in milk from challenged mammary glands than in milk from control mammary glands at 3, 5, and 7 days after challenge . Removal of casein significantly reduced bacterial growth . In general, antibodies specific to S . uberis started to increase at day 3 post-challenge and were higher in milk from challenged mammary glands than in milk from control mammary glands . There was also a marked increase in total IgG in milk from challenged mammary glands . Growth of S . uberis increased following heat treatment at 56 degrees C of pooled milk or whey samples from challenged mammary glands . Growth of S . uberis correlated negatively with the specific antibody response to the bacteria (P < 0.001) . Lactoperoxidase activity varied among cows and among different samples over time and did not appear to contribute to decreased growth of S . uberis . These results suggest that decreased growth of S . uberis in milk from challenged mammary glands in comparison to milk from control mammary glands could result from the interaction of antibodies with complement components. Vet Microbiol, 1998 Oct, 63(2-4), 261 - 74 Characterization of mechanisms involved in uptake of Streptococcus dysgalactiae by bovine mammary epithelial cells; Calvinho LF et al.; Bovine mammary epithelial cells were pretreated with inhibitors of protein kinase activity, actin polymerization and receptor-mediated endocytosis . In addition, mammary epithelial cells and Streptococcus dysgalactiae were pretreated with inhibitors of protein synthesis . Results showed that activity of tyrosine protein kinases, intact microfilaments and de novo eukaryotic protein synthesis was required for uptake of S . dysgalactiae by bovine mammary epithelial cells; a process that appeared to occur via receptor-mediated endocytosis . In contrast, de novo bacterial protein synthesis was not required for uptake of S . dysgalactiae by MAC-T cells . This study provides insight into bacterial and cellular mechanisms involved in early host-pathogen interactions, putting into perspective the role of mammary epithelial cells in the development and establishment of intramammary infections by S . dysgalactiae. Vet Microbiol, 1998 Oct, 63(2-4), 229 - 38 Simultaneous flow cytometric measurement of Streptococcus suis phagocytosis by polymorphonuclear and mononuclear blood leukocytes; Busque P et al.; A simple flow cytometric method was used to study simultaneously the phagocytosis of Streptococcus suis serotype 2 by polymorphonuclear and mononuclear blood leukocytes from swine and humans . Using this method with a bacteria-to-leukocytes ratio of 10:1 and after 60 min of incubation, 80.2 +/- 2.8% of swine granulocytes and 77.0 +/- 2.8% of swine monocytes were shown to contain FITC-labelled S . suis serotype 2 strain 735 . Using the same strain, FITC-labelled bacteria were found in 95.5 +/- 3.2% of human granulocytes and in 92.8 +/- 3.6% of human monocytes . The phagocytosis rates of avirulent and virulent strains of S . suis were not significantly different. FEMS Immunol Med Microbiol, 1998 Nov, 22(3), 225 - 31 Retention of neutralising activity by recombinant anti-pneumolysin antibody fragments; Garcia M et al.; The variable domains of a neutralising (prevents erythrocyte lysis) anti-pneumolysin monoclonal antibody have been cloned and expressed as functional protein in Escherichia coli . Purification of the anti-pneumolysin single-chain antibody fragment, via antibody-affinity or metal-chelate affinity chromatography, resulted in product that was predominantly in a dimeric or monomeric form, respectively . The dimeric single-chain antibody fragment showed a higher sensitivity and affinity for immobilised antigen in both ELISA and BIAcore studies . The dimeric single-chain antibody fragment was as effective at protecting erythrocytes from lysis as the parent monoclonal . The monomeric, low affinity single-chain antibody fragment, showed reduced neutralising potency . As antibiotic resistant Streptococcus pneumoniae strains continue to show an increasing word-wide distribution, recombinant, neutralising antibody fragments, may provide an additional class of molecules useful in the treatment of toxaemia. J Antimicrob Chemother, 1998 Nov, 42(5), 643 - 6 In-vitro activity of sanfetrinem against isolates of Streptococcus pneumoniae and Staphylococcus aureus; Johnson AP et al.; The activity of sanfetrinem (previously GV104326), was assessed against 168 isolates of Streptococcus pneumoniae and 90 isolates of Staphylococcus aureus . These isolates included a range of serotypes or phage types, and varied in their susceptibility to other antibiotics . Sanfetrinem exhibited good anti-pneumococcal activity, with MIC90s of < or = 0.007 mg/L and 0.5 mg/L for penicillin-susceptible and penicillin-resistant isolates, respectively . Sanfetrinem was also active against methicillin-susceptible staphylococci (MIC90 = 0.06 mg/L) . However, the MICs of sanfetrinem for isolates with methicillin MICs of 8-16 mg/L and > or = 32 mg/L were 0.25-1 mg/L and 8->32 mg/L, respectively. Microbiology, 1998 Nov, 144 ( Pt 11), 3069 - 78 Unconventional organization of the division and cell wall gene cluster of Streptococcus pneumoniae; Massidda O et al.; The genes responsible for cell wall biosynthesis and cell division (dcw genes) were identified and sequenced in Streptococcus pneumoniae . The genetic organization of the dcw cluster in Streptococcus pneumoniae differed significantly from the clusters of other bacteria reported to date . In particular, the genes corresponding to the 2 min region of the Escherichia coli chromosome were found distributed in three genetically separate regions of the Streptococcus pneumoniae chromosome . The first region contained the expected ftsA and ftsZ cell division genes at one end and pbp2b, ddl and murF at the other end . The murD, murG and divIB genes, always found located upstream of ftsA, were found in a second region separated from the first . A third region contained the yllC, yllD, pbp2x and mraY genes . The chromosomal region downstream of ftsZ was also sequenced and characterized . In Streptococcus pneumoniae this region contains four ORFs, all of unknown function, and an ORF encoding the Bacillus subtilis DivIVA homologue . The gene order and the organization of this region was found to be conserved in Staphylococcus aureus, Streptococcus pyogenes and Bacillus subtilis, raising the possibility that previously unidentified loci may also be involved in division. Microbiology, 1998 Nov, 144 ( Pt 11), 3061 - 8 Electrotransformation and natural transformation of Streptococcus pneumoniae: requirement of DNA processing for recombination; Lefrancois J et al.; Electrotransformation has been used as a tool to introduce genes carried on replicative vectors in hundreds of bacterial species . In this study, the technique was used to try to obtain recombination of markers in the chromosome of the naturally transformable bacterium Streptococcus pneumoniae . Recombination was not observed even using naturally competent cultures . Both chromosomal and cloned DNA, denatured or native, were without effect . These results suggest that it is not sufficient to introduce DNA into the cell to obtain recombinants in this bacterium . The integration of markers into the chromosome in naturally competent cells must require DNA processing during entry . Electrotransformation of replicating plasmids is recA-independent but can be facilitated by a recA-dependent process . This facilitation required the induction of the natural competence machinery, probably involving partial homologous pairing. Microbiology, 1998 Nov, 144 ( Pt 11), 3049 - 60 A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease; Enright MC et al.; The population biology of Streptococcus pneumoniae is poorly understood . Most of the important issues could be addressed by the molecular characterization of large, well sampled populations from carriage and from the different manifestations of pneumococcal disease . The authors have therefore developed a pneumococcal multilocus sequence typing scheme and database by sequencing approximately 450 bp fragments of seven housekeeping loci from 295 isolates . The combination of alleles at the seven loci provided an allelic profile, or sequence type (ST), and the relatedness between isolates was obtained by constructing a dendrogram from the matrix of pairwise differences between STs . The typing scheme was validated using pneumococci of known genetic relatedness and could resolve >6 billion STs . Among 274 isolates from recent cases of invasive pneumococcal disease in eight countries, 143 STs were resolved, but 12 STs contained at least five isolates (range 5-21 isolates) . The repeated recovery of indistinguishable isolates from invasive disease in different countries implies that these STs define strains with an increased capacity to cause invasive disease . The relationship between STs and serotypes suggested that, in the longer term, capsular genes have been distributed horizontally within the pneumococcal population, but in the short term, expansion of clones occurs with only occasional changes of serotype . The multilocus sequence typing scheme provides a powerful new approach to the characterization of pneumococci, since it provides molecular typing data that are electronically portable between laboratories, and which can be used to probe aspects of the population and evolutionary biology of these organisms . A Web site for the molecular characterization of pneumococci by MLST is available . Int Immunol, 1998 Nov, 10(11), 1657 - 64 Fibronectin-binding protein I of Streptococcus pyogenes promotes T cell-independent proliferation of murine B lymphocytes and enhances the expression of MHC class II molecules on antigen-presenting cells; Medina E et al.; We have previously shown that fibronectin-binding protein I (SfbI) of Streptococcus pyogenes can act as an adjuvant for mucosal-delivered antigens (Medina, E., Talay, S . R., Chhatwal, G . S . and Guzman, C . A . 1998 . Eur . J . Immunol . 28:1069) . To characterize the underlying mechanism of the adjuvancity, we investigated the in vitro stimulating activity of SfbI . The SfbI protein promoted a dose-dependent proliferation of mouse spleen cells . Studies performed using cellular subpopulations showed that proliferation involved B cells and was T cell- and macrophage-independent . SfbI also induced lg production by B cells in a T cell-independent manner . The kinetics of lg isotype accumulation in supernatant fluids and the analysis of Ig-secreting cells suggested that SfbI stimulates B cells expressing different Ig isotypes rather than promoting the isotype switching of single subpopulations . Experiments performed with recombinant proteins encompassing different functional domains of SfbI showed that the fibronectin-binding repeats were responsible for B cell activation . The sera from mice immunized by the intranasal route with SfbI did not react with either double-stranded DNA, cardiolipin or collagen . Interestingly, stimulation with Sfbl also resulted in the up-regulation of MHC class 11 molecules expression by B cells and macrophages . The elucidation of the underlying molecular events to the immunomodulatory effect exerted by SfbI will facilitate the exploitation of the potential of this molecule for the generation of mucosal vaccines. Dig Surg, 1998, 15(4), 352 - 6 Effects of closed-system drain in surgery: focus on methicillin-resistant Staphylococcus aureus; Tokunaga Y et al.; OBJECTIVE: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has made a strong impact on the strategy of peri-operative antibiotic prophylaxis, since MRSA has become one of the most common causative organisms of nosocomial infection in recent years . In this study, we conducted a bacteriological evaluation of surgical drains before and after introducing strategies to decrease MRSA infection rates . DESIGN AND PATIENTS: Between January 1987 and December 1994, we performed a total of 2, 755 surgical operations on inpatients, including 1,635 major and 1, 120 minor operations . Almost all surgical drains were examined bacteriologically when they were removed . The number of drains examined was 460 +/- 47 (mean +/- SEM) per year . Since the increased incidence of MRSA infection, we started exclusively using a closed drainage system and first-generation cephalosporins in 1991 . The strategy was evaluated by comparing the positive rates of drain cultures, changes in bacteriological features, and incidence of MRSA infection for the 4-year periods before and after 1991 . RESULTS: The positive rate of bacteria in the drains decreased significantly (p < 0.01) from 25 +/- 2 to 16 +/- 1% . Bacteriologically, the positive rate of Staphylococcus spp . decreased significantly (p < 0.05) from 7 +/- 2 to 3 +/- 0.3% . Positive rates of MRSA decreased significantly (p < 0.05) from 2.1 +/- 0.3 to 1.3 +/- 0.3% . Streptococcus declined dramatically from 3.0 +/- 0.3 to 0.3 +/- 0.1% . Of gram-negative strains, Pseudomonas and Escherichia coli were most often isolated . They showed no significant difference in positive rates between the terms . CONCLUSION: A closed drainage system and thorough use of the first-generation cephalosporins for prophylaxis were effective in decreasing positive bacterial culture of drains and reducing the incidence of MRSA on drains after surgery. FEBS Lett, 1998 Nov 20, 439(3), 263 - 6 Cloning and expression of a unique inorganic pyrophosphatase from Bacillus subtilis: evidence for a new family of enzymes; Shintani T et al.; An open reading frame located in the COTF-TETB intergenic region of Bacillus subtilis was cloned and expressed in Escherichia coli and shown to encode inorganic pyrophosphatase (PPase) . The isolated enzyme is Mn2+-activated, like the authentic PPase isolated from B . subtilis . Although 13 functionally important active site residues are conserved in all 31 soluble PPase sequences so far identified, only two of them are conserved in B . subtilis PPase . This suggests that B . subtilis PPase represents a new family of soluble PPases (a Bs family), putative members of which were found in Archaeoglobus fulgidus, Methanococcus jannaschii, Streptococcus mutans and Streptococcus gordonii. Recenti Prog Med, 1998 Nov, 89(11), 552 - 8 {Streptococcus bovis endocarditis . Clinical and microbiological observations and review of the literature}; Carfagna P et al.; Fourteen patients (11 men and 3 women) with Streptococcus bovis infective endocarditis have been observed by the Infectious Disease Section of our Department of Clinical Medicine between the years 1988-1998 . The mean age was 63.2 years (range 35-85 years); 5 patients previously suffered valvular disease or had a valvular prosthesis, the infection involved the mitral valve in 6 patients, the aortic in 8, the prosthetic valve in 1 . No patient developed cardiac failure or died during hospitalization; only 1 episode of major embolism (spleen) was observed . No patient required cardiac surgery . All patients became afebrile after starting antibiotic treatment; no cases of Streptococcus bovis relapse have been observed, during a six-month follow-up after antibiotics discontinuation, in 13 patients fully evaluated . The remaining patient was lost to follow-up . An underlying asymptomatic colonic neoplasm was diagnosed at colonoscopy in 7 of 11 evaluated patients . This study confirms that Streptococcus bovis infective endocarditis is relatively benign, but it stresses the frequency and potential severity of the associated colonic lesions, requiring colonoscopy and making the treatment of high risk lesion mandatory. J Infect Dis, 1999 Jan, 179(1), 264 - 8 Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac; Rappaport JM et al.; Pneumococcal meningitis remains a significant cause of morbidity, particularly sensorineural hearing loss . Recent literature has suggested that a vigorous host immune response to Streptococcus {corrected} pneumoniae is responsible for much of the neurologic sequelae, including deafness, after bacterial meningitis . This study used a rabbit model of hearing loss in experimental pneumococcal meningitis to evaluate the therapeutic effect of two anti-inflammatory agents, dexamethasone and ketorolac, coadministered with ampicillin . Both adjunctive drugs minimized or prevented sensorineural hearing loss compared with placebo . Dexamethasone, administered 10 min before ampicillin, was particularly effective in minimizing mean hearing threshold change compared with placebo for both clicks (dexamethasone: 6.7-dB sound pressure level {SPL} vs . placebo: 33 . 4-dB SPL, P=.0078) and 10-kHz tone bursts (dexamethasone: 8.4-dB SPL vs . placebo: 53.4-dB SPL, P=.0003) . These findings support the beneficial role of anti-inflammatory agents in reducing the incidence of hearing loss from pneumococcal meningitis, especially if therapy is instituted early in the course of infection. J Exp Med, 1998 Dec 7, 188(11), 2047 - 56 Characterization of the galU gene of Streptococcus pneumoniae encoding a uridine diphosphoglucose pyrophosphorylase: a gene essential for capsular polysaccharide biosynthesis; Mollerach M et al.; The galU gene of Streptococcus pneumoniae has been cloned and sequenced . Escherichia coli cells harboring the recombinant plasmid pMMG2 (galU) overproduced a protein that has been shown to correspond to a uridine 5'-triphosphate:glucose-1-phosphate uridylyltransferase (uridine diphosphoglucose {UDP-Glc} pyrophosphorylase) responsible for the synthesis of UDP-Glc, a key compound in the biosynthesis of polysaccharides . A gene very similar to the S . pneumoniae galU has been found in a partial nucleotide sequence of the Streptococcus pyogenes genome . Knockout galU mutants of type 1 pneumococci are unable to synthesize a detectable capsule . An identical result was found in type 3 S . pneumoniae cells in spite of the fact that these bacteria contain a type-specific gene (cap3C) that also encodes a UDP-Glc pyrophosphorylase . Since eukaryotic UDP-Glc pyrophosphorylases appear to be completely unrelated to their prokaryotic counterparts, we postulate that GalU may be an appropriate target for the search of new drugs to control the pathogenicity of bacteria like pneumococcus and S . pyogenes. Obstet Gynecol, 1998 Dec, 92(6), 931 - 4 Antibiotic susceptibility profile of group B streptococcus acquired vertically; Rouse DJ et al.; OBJECTIVE: To determine the contemporary antibiotic susceptibility profile of vertically acquired group B streptococcal isolates . METHODS: Susceptibility to ampicillin, penicillin G, erythromycin, clindamycin, cefazolin, and gentamicin was assessed by two methods, minimal inhibitory concentration and disc diffusion . RESULTS: The susceptibility profiles of 119 colonizing and eight invasive strains of group B streptococcus isolated from January 1996 to September 1997 at two hospitals in Birmingham, Alabama-University of Alabama at Birmingham and Cooper Green-were studied . Minimal inhibitory concentration determinations indicated that all colonizing strains were susceptible or moderately susceptible to ampicillin and penicillin G . Resistance was noted by at least one strain to each of the other antibiotics; all were resistant to gentamicin, whereas 27 (21%) were resistant to erythromycin, five (4%) to clindamycin, and one (1%) to cefazolin . All of the eight invasive strains were susceptible or moderately susceptible to ampicillin, penicillin G, clindamycin, and cefazolin; one (13%) was resistant to erythromycin, and all were resistant to gentamicin . Disc diffusion results generally were concordant with minimal inhibitory concentration results, although by disc diffusion fewer isolates were classified as susceptible, and more as moderately susceptible, to ampicillin and penicillin G than by minimal inhibitory concentration . CONCLUSION: Universal susceptibility of group B streptococcus to members of the penicillin family supports the continued use of penicillin G or ampicillin for early onset neonatal group B streptococcal disease prevention . For patients allergic to beta-lactam agents, clindamycin (4% resistance) may be a better alternative than erythromycin (21% resistance). Pathology, 1998 Nov, 30(4), 395 - 8 Molecular typing of multiresistant Streptococcus pneumoniae serogroup 19 in Singapore; Koh TH et al.; The prevalence of penicillin-resistant Streptococcus pneumoniae in clinical isolates from the Pathology Department of the Singapore General Hospital, in 1995, was 25% . Most of the resistant isolates belonged to serogroup 19 and were resistant to multiple antibiotics . Field-inversion gel electrophoresis (FIGE), after chromosomal digestion with the restriction enzymes Apal and Smal, was performed on all isolates of multiresistant serogroup 19 S . pneumoniae so as to determine whether they were of clonal origin . Twenty-six isolates, including six controls, were studied . Analysis of the FIGE patterns revealed three distinct clusters of closely related strains . The predominant clone comprised ten isolates of multiresistant serogroup 19 S . pneumoniae and also included two controls of a different serogroup . The presence of multiresistant serogroup 19 S . pneumoniae in Singapore, appears to be due to the spread of a small number of clones. J Reprod Med, 1998 Nov, 43(11), 1002 - 4 Intramyometrial abscess complicating pregnancy . A report of two cases; Fung TY et al.; BACKGROUND: Intramyometrial abscess in pregnancy is a rare event . Little information is available on the presentations and potential complications . CASES: Two asymptomatic patients underwent complications with failed instrumental delivery in the second stage of labor . Intramyometrial abscesses were found during lower segment cesarean section . In the first case, incision and drainage was done, and the culture of the pus revealed multiple organisms, including Escherichia coli, group B Streptococcus and Klebsiella species . The patient was successfully treated with antibiotics, while the infant did not show any evidence of infection . In the second case, removal of the abscess was performed, and pathology showed evidence of chronic abscess, but the culture did not reveal any organisms . The patient was treated with prophylactic antibiotics . The infant was treated with antibiotics for clinical sepsis, but no organism was revealed . CONCLUSION: Intramyometrial abscess complicating pregnancy can be asymptomatic . Obstructed labor can be a potential complication when the abscesses are located in the lower uterine segment . Antibiotics, together with incision and drainage or removal of the abscess, is the first choice for treatment. Biochim Biophys Acta, 1998 Nov 26, 1443(1-2), 217 - 24 Molecular structure of the gene cluster responsible for the synthesis of the polysaccharide capsule of Streptococcus pneumoniae type 33F; Llull D et al.; The organization and nucleotide sequence of the capsular gene cluster involved in the biosynthesis of the type 33F capsular polysaccharide of Streptococcus pneumoniae have been determined . The complete type 33F operon (cap33f) is composed of 14 potential open reading frames where the last ten genes are group-specific . Putative functions have been assigned to several gene products by sequence comparison with the proteins included in the databases . A functional promoter located immediately upstream from the first gene of the cap33f gene cluster has been demonstrated . A 20 kb DNA fragment containing the cap33f genes and the operon promoter was sufficient to transform a S . pneumoniae type 3 unencapsulated mutant to the type 33F capsule. J Mol Biol, 1998 Dec 11, 284(4), 1223 - 37 Self-interaction of pneumolysin, the pore-forming protein toxin of Streptococcus pneumoniae; Gilbert RJ et al.; The pathogenically important cholesterol-binding pore-formi