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Gene Review

tsst-1  -  toxic shock syndrome toxin-1

Staphylococcus aureus RF122

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Disease relevance of tsst-1


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


Biological context of tsst-1


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


Regulatory relationships of tsst-1


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


  1. Prevalence of Enterotoxin and Toxic Shock Syndrome Toxin Genes in Staphylococcus aureus Isolated from Milk of Cows with Mastitis. Srinivasan, V., Sawant, A.A., Gillespie, B.E., Headrick, S.J., Ceasaris, L., Oliver, S.P. Foodborne Pathog. Dis. (2006) [Pubmed]
  2. Toxic shock syndrome toxin-1 complexed with a class II major histocompatibility molecule HLA-DR1. Kim, J., Urban, R.G., Strominger, J.L., Wiley, D.C. Science (1994) [Pubmed]
  3. Staphylococcus aureus isolates from patients with nonmenstrual toxic shock syndrome. Evidence for additional toxins. Garbe, P.L., Arko, R.J., Reingold, A.L., Graves, L.M., Hayes, P.S., Hightower, A.W., Chandler, F.W., Broome, C.V. JAMA (1985) [Pubmed]
  4. Induction of nitric oxide synthase activity by toxic shock syndrome toxin 1 in a macrophage-monocyte cell line. Zembowicz, A., Vane, J.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  5. Separation of function between the domains of toxic shock syndrome toxin-1. Wahlsten, J.L., Ramakrishnan, S. J. Immunol. (1998) [Pubmed]
  6. The alpha 1 domain of the HLA-DR molecule is essential for high-affinity binding of the toxic shock syndrome toxin-1. Karp, D.R., Teletski, C.L., Scholl, P., Geha, R., Long, E.O. Nature (1990) [Pubmed]
  7. Toxic shock syndrome. A newly recognized complication of influenza and influenzalike illness. MacDonald, K.L., Osterholm, M.T., Hedberg, C.W., Schrock, C.G., Peterson, G.F., Jentzen, J.M., Leonard, S.A., Schlievert, P.M. JAMA (1987) [Pubmed]
  8. Protection against lethal toxic shock by targeted disruption of the CD28 gene. Saha, B., Harlan, D.M., Lee, K.P., June, C.H., Abe, R. J. Exp. Med. (1996) [Pubmed]
  9. Toxicity of staphylococcal toxic shock syndrome toxin 1 in rabbits. de Azavedo, J.C., Arbuthnott, J.P. Infect. Immun. (1984) [Pubmed]
  10. Association of toxic shock toxin-1 determinant with a heterologous insertion at multiple loci in the Staphylococcus aureus chromosome. Chu, M.C., Kreiswirth, B.N., Pattee, P.A., Novick, R.P., Melish, M.E., James, J.F. Infect. Immun. (1988) [Pubmed]
  11. A mutation at histidine residue 135 of toxic shock syndrome toxin yields an immunogenic protein with minimal toxicity. Bonventre, P.F., Heeg, H., Edwards, C.K., Cullen, C.M. Infect. Immun. (1995) [Pubmed]
  12. 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. Dinges, M.M., Gregerson, D.S., Tripp, T.J., McCormick, J.K., Schlievert, P.M. J. Infect. Dis. (2003) [Pubmed]
  13. Heterogeneity of methicillin-resistant Staphylococcus aureus strains at a German university hospital during a 1-year period. Ghebremedhin, B., König, W., König, B. Eur. J. Clin. Microbiol. Infect. Dis. (2005) [Pubmed]
  14. Subsets of HLA-DR1 molecules defined by SEB and TSST-1 binding. Thibodeau, J., Cloutier, I., Lavoie, P.M., Labrecque, N., Mourad, W., Jardetzky, T., Sékaly, R.P. Science (1994) [Pubmed]
  15. The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction. Mourad, W., Scholl, P., Diaz, A., Geha, R., Chatila, T. J. Exp. Med. (1989) [Pubmed]
  16. Identification of class II major histocompatibility complex and T cell receptor binding sites in the superantigen toxic shock syndrome toxin 1. Hurley, J.M., Shimonkevitz, R., Hanagan, A., Enney, K., Boen, E., Malmstrom, S., Kotzin, B.L., Matsumura, M. J. Exp. Med. (1995) [Pubmed]
  17. Transcytosis of staphylococcal superantigen toxins. Hamad, A.R., Marrack, P., Kappler, J.W. J. Exp. Med. (1997) [Pubmed]
  18. Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens. Leung, D.Y., Harbeck, R., Bina, P., Reiser, R.F., Yang, E., Norris, D.A., Hanifin, J.M., Sampson, H.A. J. Clin. Invest. (1993) [Pubmed]
  19. Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. Leung, D.Y., Meissner, H.C., Fulton, D.R., Murray, D.L., Kotzin, B.L., Schlievert, P.M. Lancet (1993) [Pubmed]
  20. Localization of biologic functions of toxic shock syndrome toxin-1 by use of monoclonal antibodies and cyanogen bromide-generated toxin fragments. Blomster-Hautamaa, D.A., Novick, R.P., Schlievert, P.M. J. Immunol. (1986) [Pubmed]
  21. Superantigen can reactivate bacterial cell wall-induced arthritis. Schwab, J.H., Brown, R.R., Anderle, S.K., Schlievert, P.M. J. Immunol. (1993) [Pubmed]
  22. Role of SarA in virulence determinant production and environmental signal transduction in Staphylococcus aureus. Chan, P.F., Foster, S.J. J. Bacteriol. (1998) [Pubmed]
  23. Identification of a novel two-component regulatory system that acts in global regulation of virulence factors of Staphylococcus aureus. Yarwood, J.M., McCormick, J.K., Schlievert, P.M. J. Bacteriol. (2001) [Pubmed]
  24. Cryptic alpha-toxin gene in toxic shock syndrome and septicaemia strains of Staphylococcus aureus. O'Reilly, M., Kreiswirth, B., Foster, T.J. Mol. Microbiol. (1990) [Pubmed]
  25. Staphylococcal toxic shock syndrome toxin-1 inhibits monocyte apoptosis. Bratton, D.L., May, K.R., Kailey, J.M., Doherty, D.E., Leung, D.Y. J. Allergy Clin. Immunol. (1999) [Pubmed]
  26. Modified multiplex PCR method for detection of pyrogenic exotoxin genes in staphylococcal isolates. Løvseth, A., Loncarevic, S., Berdal, K.G. J. Clin. Microbiol. (2004) [Pubmed]
  27. Induction of murine hemopoietic growth factors by toxic shock syndrome toxin-1. Galelli, A., Anderson, S., Charlot, B., Alouf, J.E. J. Immunol. (1989) [Pubmed]
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