Pyrogenic Toxin Superantigen Site Specificity in Toxic Shock Syndrome and Food Poisoning in Animals

Abstract

Staphylococcus aureus and Streptococcus pyogenes express pyrogenic toxin superantigens (PTSAgs) that are associated with toxic shock syndrome (TSS) and staphylococcal food poisoning (SFP). Most PTSAgs cause TSS in deep-tissue infections, whereas only TSS toxin 1 (TSST-1) is associated with menstrual, vaginal TSS. In contrast, SFP has been linked only with staphylococcal enterotoxins (SEs). Because of the differential abilities of PTSAgs to cause systemic or localized symptoms in a site-dependent manner, the present study was undertaken to assess the toxins' abilities to cross mucosal barriers. The activity of three PTSAgs when delivered orally, vaginally, or intravenously to rabbits and orally to monkeys was investigated. TSST-1 induced shock via all three routes in rabbits. Although active when administered intravenously, SEC1 and streptococcal pyrogenic exotoxin A (SPEA) did not cause symptoms when administered orally or vaginally. Only SEC1 induced emesis in the monkey feeding assay. TSST-1, albeit less stable than SEC1 and SPEA to pepsin, induced diarrhea in monkeys. Our results may explain the unique association of TSST-1 with menstrual TSS and why SPEA is only rarely associated with TSS after pharyngitis, despite being highly associated with TSS after subcutaneous infections. Finally, our studies indicate that enterotoxicity in SFP is not the result of superantigenicity.

Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes

“…Our current study was designed to further define residues important for the functional interaction of TSST-1 with the TCR by alanine scanning mutagenesis. Our data suggest that residues Tyr 13 136 , and Gln 139 are individually crucial for direct binding to hV␤2.1. Due to the location of these residues, we propose a model in which the MHC/TSST-1/TCR ternary complex is similar to the ternary complex of SEB, SEC, and SPE A, yet the TSST-1 complex may allow for direct interactions between the CDR3 loop of the TCR ␤-chain and TSST-1.…”

“…The slight decrease in hV␤2.1 binding seen for mutations at positions Tyr 13 , Tyr 115 , and His 141 may indicate minor involvement in the TCR/TSST-1 complex, probably through stabilizing interactions. Based on the cocrystal structure of SEC3 in contact with the mouse 14.3.d ␤-chain (21), the mutation of all SEC3 residues involved in contact with the ␤-chain revealed that only two of 12 residues (N23A, Q210A) completely lost detectable binding using their criteria for stimulatory capacity, while a third mutation (F176A) had barely detectable mitogenic activity (5).…”

“…This human TCR is specific for HTLV-I TAX [11][12][13][14][15][16][17][18][19] peptide in the context of HLA-A2.1. The expression and purification of recombinant human TCR V␤2.1J␤2.3D␤2.1C␤2 (herein referred to as hV␤2.1) were accomplished as previously described (23).…”

“…TSST-1 has been associated with TSS since 1981 (10,11), and it has been estimated that this exotoxin is responsible for ϳ50% of nonmenstrual-associated TSS cases due to S. aureus and essentially all cases of menstrual-associated TSS (12). This latter association is probably due to the apparently unique ability of TSST-1 among the pyrogenic toxin SAGs to cross mucosal surfaces (13). The crystal structure of this SAG (14,15) as well as those of many others have been determined (reviewed in Ref.…”

Lactobacillus reuteri -produced cyclic dipeptides quench agr -mediated expression of toxic shock syndrome toxin-1 in staphylococci

“…The staphylococcal superantigen TSST-1 is believed to be responsible for ∼100% of menstrual-TSS cases, which is likely related to the apparent unique ability of this particular superantigen to cross mucosal barriers (6,29). Key host and environmental factors known to influence the development of staphylococcal TSS include elevated oxygen and carbon dioxide levels, the presence of proteins, neutral pH, and 37°C (2).…”