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The superantigen toxic shock syndrome toxin-1 (TSST-1) is implicated as the major cause of staphylococcal toxic shock syndrome. The temporal sequence of early signaling events in human peripheral blood mononuclear cells following TSST-1 stimulation was examined. TSST-1 induced rapid and complete down-regulation of Vβ2-specific T cell receptor (TCR), followed by transient CD154 expression on CD4+ lymphocytes. This was sequentially followed by the upregulation of CD86, CD80, CD40, and human leukocyte antigen-DR expression on CD14+ monocytes. In contrast, S14N, a TSST-1 mutant toxin with a single amino acid substitution that is known to be impaired in interleukin (IL)-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α secretion, was deficient in both Vβ2-TCR down-regulation and CD154 and CD80/ CD86 expression. Furthermore, pretreatment with monoclonal antibodies against Vβ2-TCR, CD80/CD86, and CD154 significantly inhibited TSST-l-induced IL-2, IFN-γ and TNF-α secretion. Taken together, these results indicate that early Vβ-specific TCR activation, along with CD80/CD86 and CD154 costimulation, are key determinants of the TSST-l-induced proinfiammatory cytokine response. [ABSTRACT FROM AUTHOR]

Presents a study which examined the ability of monoclonal antibody 5 (MAb5) to cross-inhibit Staphylococcal enterotoxin A (SEA)-induced superantigenic and lethal activities both in vitro and in vivo. Materials and methods; Immunoreactivity of MAb5 with toxic shock syndrome toxin-1 and SEA; Epitope peptide mapping of MAb5 with SEA synthetic peptides.

Susceptibility of 358 clinical isolates of obligate anaerobes to metronidazole was determined by an agar-dilution technique. Only 66% of all isolates were inhibited by 6.25 µg/ml, whereas 30% required ≥ 50 µg/ml. Considerable variation in susceptibility was observed among different genera and species of bacteria. Fusobacterium was most sensitive, followed by Clostridium, Bacteroides and Peptococcus, Peptostreptococcus, Veillonella and Addaminococcus, and non-sporeforming gram-positive bacilli. Bacteroides jragilis was more sensitive than other species of Bacteroides. Similarly, Clostridium perjringens was more susceptible than other species of Clostridium. While metronidazole appears to be a promising antimicrobial agent for infections caused by Fusobacterium, Clostridium, and B. Fragilis, therapy for infections with other anaerobic bacteria should be guided by in vitro tests of sensitivity. [ABSTRACT FROM PUBLISHER]

Random mutagenesis with hydroxylamine was done on toxic shock syndrome toxin-1 (TSST-1) to identify the amino acid residues critical for binding to major histocompatibility complex (MHC) class II molecules of human monocytes. A double mutant with amino acid substitutions of glycine 31→arginine and aspartic acid 184→asparagine (G31R.D184N) demonstrated markedly reduced binding to human monocytes and induction of mitogenesis or cytokine secretion. Site-directed mutagenesis revealed that G31R, but not D184N, was at least 4 orders of magnitude less active than wild type recombinant (r) TSST-1 in these biologic activities and did not induce lethal shock in mice. The global structure of G31R remained highly similar to wild type rTSST-1 as evidenced by circular dichroism spectroscopy and binding to anti - TSST-1 polyclonal and monoclonal antibodies. These studies identified TSST-1 residue 31 as critical for binding to MHC class II molecules and for the consequent superantigenic and lethal properties of TSST-1. [ABSTRACT FROM PUBLISHER]

Toxic shock syndrome toxin 1 (TSST-l) and staphylococcal enterotoxin B (SEB) are two examples of variable genetic traits produced by Staphylococcus aureus. Regarding phenotypes, most investigations have reported that SEB and TSST-1 are not coproduced in S. aureus. However, it is unclear whether genotypically SEB (entB) and TSST-l (tst) genes are found within the same isolate. Gene probes specific for entB and tst showed that both genes were present within 8 TSST-1+ isolates analyzed. However, SEB was not produced by any of these isolates. In contrast, none of 9 SEB-producing S. aureus isolates contained the TSST-1 genetic element DNA. Hybridization of restriction fragments with TSST-1 and SEB genetic element probes and tryptophan auxotyping suggested that tst and entB are located in close proximity on the chromosome. The entB locus may be a preferred site of insertion for the TSST-1 genetic element, and such insertion may interfere with the expression of SEB. [ABSTRACT FROM PUBLISHER]

The association between staphylococcal enterotoxin (SE) B and toxic shock syndrome (TSS) toxin 1 (TSST-1) in menstrual and nonmenstrual TSS was examined. Production of SEB and TSST-1 in the culture supernatants from 344 Staphylococcus aureus isolates was quantitated by noncompetitive ELISA (lower detection limit, 0.5 ng/mL for both assays). In the ELISA for SEB, cross-reactive antibodies to SEC were removed by absorption in a biotin-streptavidin-agarose column (SEC1 at concentrations to 100,000 ng/mL could not be detected). Among TSST-1-negative isolates, SEB production in nonmenstrual TSS isolates (8/13, 62%) was more prevalent than that in either menstrual TSS isolates (1/4; P = .3), non-TSS infections (15/103, 15%; P < .001), or asymptomatic carriers (14/105, 13%; P < .001). Expression of SEB and TSST-1 was usually mutually exclusive (only 1.5% of 344 isolates produced both SEB and TSST-1). Multilocus enzyme electrophoretic typing (ET) suggested a clonal origin for both SEB- (55% of ET-5) and TSST-1 (76% of ET-19)-producing isolates. Thus, SEB may bean important cause in TSS where TSST-1 is not elaborated, especially in nonmenstrual TSS isolates. [ABSTRACT FROM PUBLISHER]

The vaginal colonization of 495 healthy women with strains of Staphylococcus aureus positive for the toxic-shock marker protein (pyrogenic exotoxic C) was examined prospectively. Production of the marker protein was detected by analytic isoelectrofocusing of culture filtrates in polyacrylamide gels (isoelectric point, 7.2). Toxicogenic strains of S. aureus were isolated from 2.6% of the women and nontoxicogenic strains from 4.0%. Vaginal carriage of toxicogenic S. aureus was found to be significantly correlated only with coisolation of Escherichia coli when a number of factors were analyzed by multivariate logistic regression and compared with values among women carrying no vaginal S. aureus or only nontoxicogenic strains (odds ratios, 8.17 and 11.02, respectively; 95% confidence intervals, 2.27–29.31 and 1.42–85.31, respectively). These data may explain the higher rate of vaginal colonization with E. coli in addition to toxicogenic S. aureus among women with toxic-shock syndrome (64%) than among age-matched control women (12%; P < .001). [ABSTRACT FROM PUBLISHER]

An outbreak of nosocomial infections involving an unusual strain of multiply resistant Proteus mirabilis (phage type 8888) occurred in 15 patients, 14 of whom were in the surgical intensive care unit at that time. No common source of infection was identified, and person-to-person transmission was the most likely mode of spread. Case-control analysis indicated a significantly increased risk of infection related to length of hospital stay (P < 0.005), number of operations (P < 0.005), proximity to another case (P < 0.01), number of antibiotics received (P < 0.02), and use of a respirator (P < 0.01). Only the number of operations (P < 0.01) and proximity to another case (P < 0.05) remained significant risk factors when related parameters were controlled by multivariate analysis. Thirteen of 14 patients prospectively cultured were colonized by the epidemic organism in the intestinal tract, while rectal carriage preceded infection by the same strain in at least four patients. These data suggest that intestinal colonization may have been an important reservoir for this outbreak, and the findings may explain the unduly prolonged course of intrahospital spread as well as the difficulty encountered in the eradication and control of the outbreak. [ABSTRACT FROM PUBLISHER]

The susceptibilities of herpes viruses to three nucleoside analogues were studied with a standardized cell-culture assay. Cytosine arabinoside (ara-C) was the most active drug; MICs were: 0.25–0.75 µg/ml for herpes simplex type 1,0.37–2.0 µg/ml for herpes simplex type 2, and 0.37–4.0 µg/ml for varicella-zoster. Adenine arabinoside (ara-A) was 20-fold less active against herpes simplex and varicella-zoster. Ara-A demonstrated an additive effect with ara-C and with 5-iodo-2′-deoxyuridine (IUDR) against herpes simplex type 1; ara-C and IUDR were antagonistic. The MIC of ara-C for 80% plaque-reduction of cytomegalovirus was 2.0–4.0 µg/ml; none of the drugs inhibited cytomegalovirus by 100%. The MICs of all three nucleoside analogues against herpes simplex virus were considerably higher when assayed at pH 8.0 rather than at pH 7.0. Herpes simplex type 2 was significantly more resistant to IUDR than herpes simplex type 1 only when tested in a strongly buffered alkaline medium. The usefulness of these in vitro antiviral assays, however, has to be demonstrated by further laboratory and clinical studies. [ABSTRACT FROM PUBLISHER]