Disease relevance of tsst-1

• Staphylococcus aureus isolated from milk of cows with mastitis were evaluated for the prevalence of 16 enterotoxin genes (sea-see and seg-seq) and toxic shock syndrome toxin gene (tsst-1) [1].
• The three-dimensional structure of a Staphylococcus aureus superantigen, toxic shock syndrome toxin-1 (TSST-1), complexed with a human class II major histocompatibility molecule (DR1), was determined by x-ray crystallography [2].
• Seven of the TSST-1-negative strains were evaluated in a rabbit subcutaneous chamber model of toxic shock syndrome [3].
• Thus, TSST-1 and perhaps other exotoxins produced by Gram-positive bacteria induce NO synthase and the increased NO formation may contribute to toxic shock syndrome and possibly to changes in the immune responses that accompany infection [4].
• In this study, we expressed the individual N- and C-terminal domains of TSST1 in Escherichia coli and studied their biologic activities [5].

High impact information on tsst-1

• Using chimaeric alpha- and beta-chains of DR and DP expressed at the surface of transfected murine fibroblasts and a binding assay with TSST-1, it was shown that the alpha 1 domain of DR is essential for high-affinity binding, and further that TSST-1 binding did not prevent subsequent binding of a DR-restricted antigenic peptide [6].
• Whereas SEB binds primarily off one edge of the peptide binding site of DR1, TSST-1 extends over almost one-half of the binding site and contacts both the flanking alpha helices of the histocompatibility antigen and the bound peptide [2].
• Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1 [2].
• Seven S aureus isolates were available for determination of exotoxin production; five isolates produced toxic shock syndrome toxin-1, one produced enterotoxin B, and one produced both [7].
• These results suggest that other, as yet unrecognized, toxins play a role in toxic shock syndrome, and that TSST-1 production may not be essential to the pathogenesis of toxic shock syndrome [3].

Chemical compound and disease context of tsst-1

• Nearly 90% of the clinical cases of TSS arise due to an exotoxin, toxic shock syndrome toxin-1 (TSST-1), elaborated by toxigenic strains of Staphylococcus aureus [8].
• Strains of Staphylococcus aureus associated with toxic shock syndrome produce toxic shock syndrome toxin 1 (TSST 1), which is lethal to conventional rabbits and acts synergistically with gram-negative lipopolysaccharide [9].
• The association between TSST-1 production and tryptophan auxotrophy was not correlated with the phage type, the colonization site, or the disease status of the patient from whom the isolate came [10].
• A mutation at histidine residue 135 of toxic shock syndrome toxin yields an immunogenic protein with minimal toxicity [11].
• Effects of total body irradiation and cyclosporin a on the lethality of toxic shock syndrome toxin-1 in a rabbit model of toxic shock syndrome [12].

Biological context of tsst-1

• Selected isolates were typed by multilocus sequence typing (MLST), by a multiplex polymerase chain reaction (PCR) for the staphylococcal cassette chromosome mec (SCCmec), by an allele-specific PCR for the staphylococcal accessory gene regulator (agr), and by PCR for the presence of toxin genes (sea-sej, tsst-1, hlgA, C, and B, lukE/D, and luk-pvl) [13].
• The high prevalence of enterotoxin genes and tsst-1 in S. aureus may be important as it is relevant to udder pathogenicity and food hygiene [1].
• Here, a mutation in the peptide-binding groove disrupted the SEB and TSST-1 binding sites, which suggests that peptides can influence the interaction with bacterial toxins [14].
• TSST-1 bound to tonsilar B cells with high affinity and saturation kinetics [15].
• To characterize these interactions at the molecular level, random point mutations were generated in the gene encoding toxic shock syndrome toxin 1, a bacterial superantigen associated with toxic shock syndrome [16].

Anatomical context of tsst-1

• The hierarchy of TSST-1 resistance among CD28 wild-type (CD28+/+), CD28 heterozygous (CD28+/-), and CD28-/- mice suggests a gene-dose effect, implying that the levels of T cell surface CD28 expression critically regulate superantigen-mediated costimulation [8].
• The Staphylococcus aureus exotoxin toxic shock syndrome toxin 1 (TSST-1) is a potent activator of T cells and monocytes [15].
• In the present study, we have examined the effect of TSST-1 on the activation and differentiation of high density human tonsillar B cells [15].
• We found that Caco-2 cells are capable of dose-dependent, facilitated transcytosis of SEB and TSST-1, but not SEA [17].
• Freshly isolated basophils from 10 AD patients released 5-59% of total histamine in response to SEA, SEB, or TSST-1 but only with toxins to which patients had specific IgE [18].

Associations of tsst-1 with chemical compounds

• All TSST-producing KS isolates were tryptophan auxotrophs indicating they were clonally related [19].
• J774.2 macrophages stimulated with TSST-1 (10-100 nM) generated nitrite, a breakdown product of NO, and induced concentration-dependent elevations of cGMP in the pig kidney epithelial cell line (LLC-PK1) [4].
• Hydrocortisone (1 microM) but not indomethacin (5 micrograms/ml) or salicylic acid (5 micrograms/ml) prevented the generation of NO2- and the increases in cGMP levels in LLC-PK1 cells induced by J774.2 cells stimulated with TSST-1 [4].
• Localization of biologic functions of toxic shock syndrome toxin-1 by use of monoclonal antibodies and cyanogen bromide-generated toxin fragments [20].
• Cyclosporin A suppresses all phases of the recurrent arthritis, indicating that TSST-1 could be functioning through its property of a superantigen activating T lymphocytes [21].

Regulatory relationships of tsst-1

• Transcriptional gene fusion and Western analysis revealed that sarA up-regulates both toxic shock syndrome toxin 1 gene (tst) expression and staphylococcal enterotoxin B production, respectively [22].

Other interactions of tsst-1

• The majority of S. aureus isolated from milk of mastitic cows carried newly described SE genes sem, sen and sei along with classical SE genes, sed and tsst-1 [1].
• Disruption of srrB resulted in decreased production of TSST-1 under microaerobic conditions and, to a lesser extent, under aerobic conditions as well [23].
• The hla gene was cloned from an Hla- TSST-1+ strain, Todd 555, which had been isolated from a case of toxic shock syndrome in the USA [24].
• OBJECTIVE: We sought to determine whether the staphylococcal exotoxin, toxic shock syndrome toxin-1 (TSST-1), could stimulate prosurvival cytokine production in monocytes and thereby inhibit apoptosis [25].
• A modified multiplex PCR method for detection of nine Staphylococcus aureus enterotoxin genes (sea, seb, sec, sed, see, seg, seh, sei, and sej) and one form of immunoreactive toxic shock syndrome toxin based on a previously published method (S. R. Monday and G. A. Bohach, J. Clin. Microbiol. 37:3411-3414, 1999) has been developed [26].

Analytical, diagnostic and therapeutic context of tsst-1

• The secreted toxins of S. aureus grown from AD patients were identified by ELISA using antibodies specific for staphylococcal enterotoxin (SE) exfoliative toxin (ET), or toxic shock syndrome toxin (TSST-1) [18].
• We used the murine monocyte-macrophage cell line J744.2 that responds to TSST-1 and also expresses NO synthase activity upon immunological stimulation [4].
• The Western blot analysis showed that the mitogenic and the suppressive functions of TSST-1 were located on a 14,000 dalton internal CNBr fragment [20].
• Intravenous injection of toxic shock syndrome toxin-1 (TSST-1) produced by Staphylococcus aureus, can reactivate arthritis in a rat ankle joint that has been previously inflamed by injection of peptidoglycanpolysaccharide polymers isolated from the cell walls of group A streptococci [21].
• Furthermore, in spleen cell cultures from normal mice, TSST-1 and LPS did not act synergistically to induce CSF activity [27].

References