Immune Cell Activation by Enterotoxin Gene Cluster (egc)-Encoded and Non-egc Superantigens from Staphylococcus aureus

Grumann, Dorothee; Scharf, Sandra S.; Holtfreter, Silva; Köhler, Christian; Steil, Leif; Engelmann, Susanne; Hecker, Michael; Völker, Uwe; Bröker, Barbara M.

doi:10.4049/jimmunol.181.7.5054

Cited by 63 publications

(57 citation statements)

References 44 publications

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“…The expression of each of these genes by S. aureus is precisely controlled by several regulatory systems but in a different manner (28). As suggested by Grumann et al, we suspect that it is beneficial for S. aureus to extend the conditions when the immune system is triggered by SSAgs (13).…”

Section: Discussionmentioning

confidence: 74%

Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns

et al. 2009

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Staphylococcus aureus can produce a wide variety of exotoxins, including toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxins, and staphylococcal enterotoxin-like toxins. These toxins share superantigenic activity. To investigate the ␤ chain (V␤) specificities of each of these toxins, TSST-1 and all known S. aureus enterotoxins and enterotoxin-like toxins were produced as recombinant proteins and tested for their ability to induce the selective in vitro expansion of human T cells bearing particular V␤ T-cell receptors (TCR). Although redundancies were observed between the toxins and the V␤ populations, each toxin induced the expansion of distinct V␤ subsets, including enterotoxin H and enterotoxin-like toxin J. Surprisingly, the V␤ signatures were not associated with a specific phylogenic group of toxins. Interestingly, each human V␤ analyzed in this study was stimulated by at least one staphylococcal superantigen, suggesting that the bacterium derives a selective advantage from targeting the entire human TCR V␤ panel.Staphylococcus aureus produces a broad range of exoproteins, including staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin 1 (TSST-1) (9). These toxins were initially implicated in staphylococcal food poisoning (SEs) and TSS (TSST-1) (39). Since the first characterization of SEA and SEB in 1959 to 1960 by Casman and Bergdoll, 18 different SEs have been described; they are designated SEA to SEV, in the chronological order of their discovery (2,5,41). Some were renamed SE-like toxins (SEl), because either no emetic properties were detected or because they were not tested in primate models (21, 41).SEs, SEls, and TSST-1 share certain structural and biological properties. They have similar sizes (23 to 29 kDa), and their crystal structures, established for SEA, SEB, SEC, SED, SEH, SElI, SElK, and TSST-1, reveal significant homology in their secondary and tertiary conformations (26).

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Section: Discussionmentioning

confidence: 74%

Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns

et al. 2009

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“…Remarkably, the regulation of SAg release differs fundamentally between the two groups of SAgs (10,31). These findings raised the question of how this differential regulation of egc and non-egc SAgs affects the antiSAg antibody response during SAB.…”

Section: Discussionmentioning

confidence: 99%

“…to egc and non-egc SAgs (10). Because the amino acid sequences of the egc SAgs are more closely related to those of individual non-egc SAgs than to each other (17,42), it also appears unlikely that the two groups of SAgs differ systematically in their immunogenicities.…”

Section: Vol 18 2011 Superantigens In S Aureus Bacteremia 491mentioning

confidence: 99%

“…The bacterial supernatants were collected at the stationary growth phase from cultures of the infecting S. aureus isolates grown in tryptone soy broth medium. The recombinant SAgs were produced in Escherichia coli and were efficiently lipopolysaccharide (LPS) depleted as described before (10). T cell proliferation assays were performed in RPMI 1640 supplemented with 10% fetal bovine serum (FBS) using peripheral blood mononuclear cells (PBMCs) from three different, healthy blood donors.…”

Section: Methodsmentioning

confidence: 99%

“…This "egc gap" in the antibody response of healthy individuals was unexpected because of the high prevalence of egc SAg genes in clinical S. aureus isolates (4,9,14). A comparison of recombinant egc and non-egc SAgs revealed that they do not differ in any of the studied aspects of T cell activation, including gene regulation, cytokine secretion, or induction of T cell proliferation (10). Remarkably, egc SAgs are secreted by S. aureus during exponential growth in vitro, whereas non-egc SAgslike most virulence factors-are expressed during stationary growth (10, 31).…”

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Characterization of Infecting Strains and Superantigen-Neutralizing Antibodies in Staphylococcus aureus Bacteremia

Grumann

Ruotsalainen

Kolata

et al. 2011

Clin Vaccine Immunol

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Staphylococcus aureus superantigens (SAgs) are highly potent T cell mitogens. Antibodies against nonenterotoxin gene cluster (non-egc) SAgs are common in healthy adults, whereas neutralizing antibodies against egc SAgs are rare. We investigated the infecting S. aureus strains and the anti-SAg antibody response during S. aureus bacteremia (SAB). This prospective clinical study (www.clinicaltrials.gov, NCT00548002) included 43 injection drug users (IDUs) and 44 group-matched nonaddicts with SAB. spa genotypes and SAg gene patterns (multiplex PCR) of the S. aureus isolates were determined. The neutralizing capacities of sera obtained at the acute phase and the convalescent phase of SAB were tested against the SAg cocktail of the respective infecting strain and a panel of recombinant SAgs. The lineages CC59 and CC30 were more prevalent among bacteremia strains from IDUs than among strains from nonaddicts. SAg gene patterns in isolates from IDUs and nonaddicts were similar. At the acute phase of bacteremia, IDUs had more neutralizing antibodies against non-egc SAgs than did nonaddicts. Antibody titers frequently increased during infection. In contrast, there were no neutralizing antibodies against egc SAgs at disease onset and such antibodies were not induced by SAB. SAB triggers an antibody response only against non-egc SAgs. Preimmunization in IDU patients is probably due to previous exposure to the infecting strain.Staphylococcus aureus is a major human pathogen that causes a wide spectrum of infections, such as toxin-mediated diseases and systemic infections, for instance, bacteremia and endocarditis. At the same time, S. aureus is a commensal that colonizes approximately 35% of the healthy population in the nose (46,48).Among the numerous toxins of S. aureus are the 21 known staphylococcal superantigens (SAgs): the toxic shock syndrome toxin (TSST-1), the staphylococcal enterotoxins (SEA to SEE and SEG to SEJ), and the staphylococcal enterotoxin-like toxins (SElK to SElU) (13,24,33,35,38). They are encoded on mobile genetic elements, like phages and pathogenicity islands (25). SAgs are the causative agents of food poisoning and toxic shock syndrome, but their role in bacteremia is not well defined (13, 28). They can activate a large fraction of T lymphocytes by directly cross-linking certain T cell receptor V␤ domains with conserved structures on major histocompatibility complex class II (MHC II) molecules. This results in a polyclonal T cell activation and massive cytokine release.The more recently described enterotoxin gene cluster (egc) harbors five or six SAg genes (seg, sei, selm, seln, selo, and sometimes selu), which cluster on a staphylococcal pathogenicity island (Sa␤) (17,23). In contrast to the non-egc SAgs, the egc is organized as an operon, and its genes are transcribed into a polycistronic mRNA (17). The egc genes are the most prevalent SAg genes in commensal and invasive S. aureus isolates, with frequencies ranging between 52 and 66% (4, 9, 14).

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Staphylococcus

Hermans

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Haesebrouck

2010

Pathogenesis of Bacterial Infections in Animals

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Immune Cell Activation by Enterotoxin Gene Cluster (egc)-Encoded and Non-egc Superantigens from Staphylococcus aureus

Cited by 63 publications

References 44 publications

Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns

Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns

Characterization of Infecting Strains and Superantigen-Neutralizing Antibodies in Staphylococcus aureus Bacteremia

Staphylococcus

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