Molecular structure of staphylococcus and streptococcus superantigens

Abstract

Staphylococcus aureus and streptococci, notably those belonging to group A, make up a large family of true exotoxins referred to as pyrogenic toxin superantigens. These toxins cause toxic shock-like syndromes and have been implicated in several allergic and autoimmune diseases. Included within this group of proteins are the staphylococcal enterotoxins, designated serotypes A, B, Cn, D, E, and G; two forms of toxic shock syndrome toxin-1 also made by Staphylococcus aureus; the group A streptococcal pyrogenic exotoxins, serotypes A, B, and C; and recently described toxins associated with groups B, C, F, and G streptococci. The nucleotide sequences of the genes for all of the toxins except those from the groups B, C, F, and G streptococcal strains have been sequenced. The sequencing studies indicate that staphylococcal enterotoxins B and C and streptococcal pyrogenic exotoxin A share highly significant sequence similarity; staphylococcal enterotoxins A, D, and E share highly significant sequence similarity; and toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxin B and C share little, if any, sequence similarity with any of the toxins. Despite the dissimilarities seen in primary amino acid sequence among some members of the toxin family, it was hypothesized that there was likely to be significant three-dimensional structure similarity among all the toxins. The three-dimensional structures of three of the pyrogenic toxin superantigens have been determined recently. The structural features of two of these, toxic shock syndrome toxin-1 and enterotoxin C3, are presented. Toxic shock syndrome-1 exists as a protein with two major domains, referred to as A and B. The molecule begins with a short N-terminal alpha-helix that then leads into a clawshaped structure in domain B that is made up of beta strands.

Inhibition of Staphylococcal Enterotoxin B-Induced Lymphocyte Proliferation and Tumor Necrosis Factor Alpha Secretion by MAb5, an Anti-Toxic Shock Syndrome Toxin 1 Monoclonal Antibody

“…Staphylococcal and streptococcal toxins, including toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxin (SE) serotypes A, B, C1 to C3, D, E, G, and H, and streptococcal pyrogenic exotoxin (SPE) serotypes A, B, and C, are known as pyrogenic toxin superantigens (PTSAgs) (31). They can cause profound disturbances in the homeostasis of the immune system, including massive proliferation of T cells bearing specific V␤ elements on their receptors, and an uncontrolled release of proinflammatory cytokines such as interleukin-1␣ (IL-1␣), IL-1␤, IL-2, IL-4, IL-6, and IL-10, gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣) and TNF-␤, and others (9,24,28).…”

“…Biochemically, all PTSAgs are small polypeptides of approximately 22 to 30 kDa, with a neutral to basic isoelectric point (31). They are generally resistant to acid, heat, and protease digestion (2).…”

“…Primary amino acid sequence alignment analysis also suggests the presence of conserved sequences among these PTSAgs. For example, based on these sequences, PTSAgs can be separated into two predominant groups in which members share at least 50% sequence similarity: group 1, consisting of SE serotype B (SEB), SEC1 to -3, and SPEA; and group 2, consisting of SEA, SED, and SEE (1,31). In contrast, TSST-1, SPEB, and SPEC share little (generally Ͻ25%), if any, sequence similarity with the other toxins (31).…”

Development of serum IgM antibodies against superantigens ofStaphylococcus aureusandStreptococcus pyogenesin Kawasaki disease

“…These disparities of kind and number of SAgs involved may be due to the following differences; ages of control subjects, immunological classes in analyses, ELISA methods, the timing of blood collection, and geographical populations. Alternatively, because of molecular mimicry between SEB, SEC, and SPEA [17,18], crossreacted IgG or IgM antibodies [19,20] might be detected in our study. In any case, the specific organism may not be as important as a common mechanism of stimulation to develop the immune system.…”

HLA-DQ6 and ingestion of contaminated water: possible gene–environment interaction in an outbreak of Leptospirosis

“…Such widespread T-cell activation has been demonstrated in other superantigen-mediated diseases such as staphylococcal and streptococcal toxic shock 45 and Kawasaki syndrome, 46 which often present with fever, rash, mucosal inflammation and multiorgan system dysfunction-classical clinical features of leptospirosis. Since superantigens bind HLA sequences conserved across many alleles within a serogroup, this model would also be consistent with an association between HLA-DQ6 and seropositivity that is not allele-specific.…”