title: Staphylococcus aureus isolates encode variant staphylococcal enterotoxin B proteins that are diverse in superantigenicity and lethality.
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.
authors: Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
authors: Petra L
authors: PL
authors: Kohler
authors: Seth D
authors: SD
authors: Greenwood
authors: Suba
authors: S
authors: Nookala
authors: Malak
authors: M
authors: Kotb
authors: David M
authors: DM
authors: Kranz
authors: Patrick M
authors: PM
authors: Schlievert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D003001:Cloning, Molecular; D004768:Enterotoxins / Q000378:metabolism*; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000378:metabolism*; D018089:Superantigens / Q000378:metabolism
chemical_list: D004768:Enterotoxins; D010455:Peptides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal