Staphylococcus aureus isolates encode variant staphylococcal enterotoxin B proteins that are diverse in superantigenicity and lethality

Petra L. Kohler, Seth D. Greenwood, Suba Nookala, Malak Kotb, David M. Kranz, Patrick M. Schlievert

Research output: Contribution to journalArticle

Abstract

Staphylococcus aureus produces superantigens (SAgs) that bind and cross-link T cells and APCs, leading to activation and proliferation of immune cells. SAgs bind to variable regions of the β-chains of T cell receptors (Vβ-TCRs), and each SAg binds a unique subset of Vβ-TCRs. This binding leads to massive cytokine production and can result in toxic shock syndrome (TSS). The most abundantly produced staphylococcal SAgs and the most common causes of staphylococcal TSS are TSS toxin-1 (TSST-1), and staphylococcal enterotoxins B and C (SEB and SEC, respectively). There are several characterized variants of humans SECs, designated SEC1-4, but only one variant of SEB has been described. Sequencing the seb genes from over 20 S. aureus isolates show there are at least five different alleles of seb, encoding forms of SEB with predicted amino acid substitutions outside of the predicted immune-cell binding regions of the SAgs. Examination of purified, variant SEBs indicates that these amino acid substitutions cause differences in proliferation of rabbit splenocytes in vitro. Additionally, the SEBs varied in lethality in a rabbit model of TSS. The SEBs were diverse in their abilities to cause proliferation of human peripheral blood mononuclear cells, and differed in their activation of subsets of T cells. A soluble, high-affinity Vβ-TCR, designed to neutralize the previously characterized variant of SEB (SEB1), was able to neutralize the variant SEBs, indicating that this high-affinity peptide may be useful in treating a variety of SEB-mediated illnesses.

Original languageEnglish (US)
Article numbere41157
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 16 2012

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superantigens
septic shock
Superantigens
enterotoxins
Staphylococcus aureus
Poisons
Septic Shock
T-cells
T-lymphocytes
amino acid substitution
Amino Acid Substitution
Proteins
Substitution reactions
proteins
Chemical activation
rabbits
Rabbits
Amino Acids
T-Lymphocyte Subsets
mononuclear leukocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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Staphylococcus aureus isolates encode variant staphylococcal enterotoxin B proteins that are diverse in superantigenicity and lethality. / Kohler, Petra L.; Greenwood, Seth D.; Nookala, Suba; Kotb, Malak; Kranz, David M.; Schlievert, Patrick M.

In: PloS one, Vol. 7, No. 7, e41157, 16.07.2012.

Research output: Contribution to journalArticle

Kohler, Petra L. ; Greenwood, Seth D. ; Nookala, Suba ; Kotb, Malak ; Kranz, David M. ; Schlievert, Patrick M. / Staphylococcus aureus isolates encode variant staphylococcal enterotoxin B proteins that are diverse in superantigenicity and lethality. In: PloS one. 2012 ; Vol. 7, No. 7.
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