Staphylococcal enterotoxins (SE) can cause toxin-mediated disease, and those that function as superantigens are implicated in the pathogenesis of allergic diseases. The prevalence of 19 enterotoxin genes was determined by PCR in clinical S. aureus strains derived from wounds (108) and blood (99). We performed spa typing and multilocus sequence typing (MLST) to determine clonal origin, and for selected strains staphylococcal enterotoxin B (SEB) production was measured by enzyme-linked immunosorbent assay. Strains carried a median of five SE genes. For most SE genes, the prevalence rates among methicillinresistant and methicillin-sensitive S. aureus isolates, as well as wound-and blood-derived isolates, did not differ. At least one SE gene was detected in all except two S. aureus isolates (>99%). Complete egc clusters were found in only 11% of S. aureus isolates, whereas the combination of sed, sej, and ser was detected in 24% of clinical strains. S. aureus strains exhibited distinct combinations of SE genes, even if their pulsed-field gel electrophoresis and MLST patterns demonstrated clonality. USA300 strains also showed considerable variability in SE content, although they contained a lower number of SE genes (mean, 3). By contrast, SE content was unchanged in five pairs of serial isolates. SEB production by individual strains varied up to 200-fold, and even up to 15-fold in a pair of serial isolates. In conclusion, our results illustrate the genetic diversity of S. aureus strains with respect to enterotoxin genes and suggest that horizontal transfer of mobile genetic elements encoding virulence genes occurs frequently.As a commensal, Staphylococcus aureus colonizes the nasal mucosa of 20 to 40% of humans (54), and as a pathogen it causes pyogenic diseases and toxin-mediated diseases (38). S. aureus produces many different virulence factors, including enterotoxins (SEs), which can cause defined toxic shock syndromes (4). The characterization of some of these toxins led to the discovery of superantigens (41), which bind to major histocompatibility complex class II molecules and V␤ chains of T-cell receptors, resulting in the activation of large numbers of T cells (20 to 30%) and massive cytokine production (10, 18). These superantigen-induced "cytokine storms" are responsible for the toxic effects seen in staphylococcal entertoxin B (SEB)-and toxic shock syndrome toxin (TSST)-associated shock syndromes in S. aureus infections (13, 40, 47). To date, 19 SEs have been identified based on sequence homologies, and studies have reported enterotoxin genes in up to 80% of all S. aureus strains (4, 21). Although many new enterotoxins have been identified, i.e., seg ser and seu (33,37,44,49), their precise functions have not been characterized yet. The majority of experimental work with SEs is still done with SEB, toxic shock syndrome toxin 1, and SEA (27, 31), because these toxins are commercially available. Most SEs are located on mobile elements in bacterial genomes such as plasmids or pathogenicity islands and can thu...

lukF-PV was present in 36% of skin and soft tissue infection (SSTI)-derived methicillin-susceptible Staphylococcus aureus (MSSA) strains and comprised six distinct clones, which contained fewer enterotoxin genes than strains without lukF-PV. Clinical presentations and outcomes of lukF-PV ؉ methicillin-resistant S. aureus (MRSA) and MSSA SSTIs were comparable. In multivariable analysis, the presence of lukF-PV remained a significant predictor for incision and drainage among MSSA strains.In the United States, Panton-Valentine leukocidin (PVL), a pore-forming cytotoxin, is investigated mostly in the emerging community-acquired methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 (10). PVL contribution to virulence is disputed, as summarized by Schlievert (6). PVL is also produced by strains other than USA300, and levels vary considerably among individual strains (2, 8). Some methicillinsusceptible S. aureus (MSSA) strains produce large amounts of PVL, which has been associated with more-severe skin lesions in a murine model (8). In this study, we compared the prevalences of PVL in MSSA and MRSA strains from patients with skin and soft tissue infections (SSTIs) and compared the clinical presentations. S. aureus isolates from wound (n ϭ 108) and blood (n ϭ 99) were collected by the microbiology laboratory of Montefiore Medical Center as described previously (9). Detection of enterotoxin genes (staphylococcal enterotoxin A [SEA], SEB, SEC, and toxic shock syndrome toxin [TSST] genes), multilocus sequence typing (MLST), and spa typing were done in the context of a previously published study (9). For this study, detection of PVL in MSSA isolates was performed by real-time PCR targeting the lukF-PV gene (7). Also, a retrospective chart review was performed on all 104 patients from whom wound isolates had been collected and 11 patients from whom PVL-producing S. aureus strains were cultured from blood. Information on demographic characteristics, clinical presentation, antibiotic therapy, complications, and outcomes was obtained. Fever was defined as greater than 38.0°C and leukocytosis as Ն12.0 K/l. Health care-associated (HA) risk factors included end-stage renal disease (ESRD) on dialysis, hospitalization 6 months prior to admission, history of S. aureus infection, and nursing home residence. The Wilcoxon rank-sum test was used to compare continuous variables, and the 2 or Fisher exact test was used to compare proportions. To assess the outcome variable of incision and drainage, selected predictor variables whose P values were less than 0.20 in univariate analysis were introduced into a multivariate logistic regression model for further analysis.Chart review determined that 101 wound isolates were derived from patients with SSTIs (46 on extremities, 55 from other body parts). Clinical data from 4 patients were not retrievable, and 3 wound isolates were excluded as they were grown from infected bone biopsy specimens and an infected vascular graft. MSSA and MRSA strains were isolated in 57% and 43% of SSTI case...

Staphylococcal enterotoxin B (SEB) is a select agent because it is a potent mitogen that elicits life-threatening polyclonal T-cell proliferation and cytokine production at very low concentrations. Efforts are in progress to develop therapeutic reagents and vaccines that neutralize or prevent the devastating effects of this toxin. Because of its rapid binding to in vivo receptors, this toxin is difficult to detect in serum. This rapid binding also constitutes a major challenge for the development of effective therapeutic reagents that can neutralize the effects of the toxin in vivo. We have developed a highly sensitive capture enzyme-linked immunosorbent assay that detects SEB in body fluids at very low levels. With this assay, the peak levels of SEB in serum and renal clearance can be measured in mice. After either oral ingestion or nasal inhalation of SEB by mice, this assay documents the transcytosis of SEB across the mucosal membranes into serum within 2 h. Furthermore, this assay was used to compare the SEB levels in different murine models for SEB-induced lethal shock and demonstrated that the coadministration of toxinenhancing chemicals, such as D-galactosamine and lipopolysaccharide, can alter the peak serum SEB levels. Hence, this assay is a potentially useful tool for the study of the pharmacokinetics of SEB and the effects of potential therapeutic reagents on serum SEB levels.The staphylococcal enterotoxins compromise a family of distinct toxins (toxins A to E) that are excreted by various strains of Staphylococcus aureus (12). Staphylococcal enterotoxin B (SEB) is the primary cause of food poisoning, and ingestion of SEB induces emesis and diarrhea. At low serum concentrations, SEB can trigger toxic shock, profound hypotension, and multiorgan failure. SEB is the major enterotoxin associated with nonmenstrual toxic shock syndrome and accounts for the majority of intoxications that are not caused by toxic shock syndrome toxin 1 (TSST-1) (17).SEB is a well-characterized 28-kDa protein that is most closely related to SEC and the streptococcal pyrogenic exotoxins A and C (12, 33). Like all of the aforementioned toxins, SEB is a superantigen and is one of the most potent mitogens described. SEB mediates its biological effects by binding to the major histocompatibility complex (MHC) class II complex at a distinct site and is different from other antigens in that it does not have to be preprocessed. The toxin is presented to a T-cell antigen receptor by an MHC class II molecule, forming ternary complexes that trigger cytokine production and T-cell proliferation (5, 13, 18, 33).During the 1960s, when the United States had an offensive biological warfare program, SEB, then code named PG, was studied extensively as a biological incapacitant. The toxin was especially attractive as a biological agent because much lower quantities of SEB than of synthetic chemicals were needed to produce intoxicating effects. The dose of SEB that is incapacitating for 50% of the human population exposed to SEB was predicted to be ...