Recombinant epidermolytic (exfoliative) toxin A of Staphylococcus aureus is not a superantigen

Fleischer, Bernhard; Bailey, Christopher J.

doi:10.1007/bf00191548

Cited by 31 publications

(16 citation statements)

References 18 publications

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“…Two of the major goals of this study were to definitively assign the superantigen activity we found to the molecule and to differentiate SSA, structurally and functionally, from previously characterized staphylococcal or streptococcal superantigens. Controversy exists regarding the assignment ofsuperantigen activity to several staphylococcal and streptococcal molecules, including SPE-B (35), due to possible contaminants in the preparations (36,37). Assignment of V(B specificities to certain superantigens has apparently also suffered from use of contaminated samples (5).…”

Section: Discussionmentioning

confidence: 99%

A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C.

Mollick¹,

Miller²,

Musser³

et al. 1993

J. Clin. Invest.

150

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Streptococcus pyogenes (group A Streptococcus) has reemerged in recent years as a cause of severe human disease. Because extracellular products are involved in streptococcal pathogenesis, we explored the possibility that a disease isolate expresses an uncharacterized superantigen. We screened culture supernatants for superantigen activity with a major histocompatibility complex class II-dependent T cell proliferation assay. Initial fractionation with red dye A chromatography indicated production of a class II-dependent T cell mitogen by a toxic shock-like syndrome (TSLS) strain. The amino terminus of the purified streptococcal superantigen was more homologous to the amino termini of staphylococcal enterotoxins B, C1, and C3 (SEB, SEC,, and SEC3), than to those of pyrogenic exotoxins A, B, C or other streptococcal toxins. The molecule, designated SSA, had the same pattern of class II isotype usage as SEB in T cell proliferation assays. However, it differed in its pattern of human T cell activation, as measured by quantitative polymerase chain reaction with Va-specific primers. SSA activated human T cells that express V#1, 3, 15 with a minor increase of V#5.2-bearing cells, whereas SEB activated V,63, 12, 15, and 17-bearing T cells. Immunoblot analysis of 75 disease isolates from several localities detected SSA production only in group A streptococci, and found that SSA is apparently confined to only three clonal lineages as defined by multilocus enzyme electrophoresis typing. Isolates of one of these lineages, (electrophoretic type 2) are strongly associated with TSLS. The data identify SSA as a novel streptococcal superantigen that appears to be more related structurally to staphylococcal enterotoxins than to streptococcal exotoxins. Because abundant SSA production is apparently confined to only three streptococcal clonal lineages, the data also suggest that the SSA gene has only recently been acquired by S. pyogenes. (J. Clin.

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Section: Discussionmentioning

confidence: 99%

A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C.

Mollick¹,

Miller²,

Musser³

et al. 1993

J. Clin. Invest.

150

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“…In their 1992 report Fleischer and Bailey could not demonstrate a mitogenic response from rETA expressed in S. aureus (7). They conclude that the activity seen by the other groups was caused by contamination of the commercial preparations used.…”

mentioning

confidence: 95%

“…Previously, Fleischer and Bailey reported that recombinant ETA expressed in a superantigen-free S. aureus background does not have mitogenic activity (7). They conclude that the activity seen by others is due to contamination of the toxin preparations with other superantigens.…”

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confidence: 96%

RecombinantStaphylococcus aureusExfoliative Toxins Are Not Bacterial Superantigens

et al. 2000

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Staphylococcal scalded-skin syndrome is an exfoliative dermatitis characterized by the separation of the epidermis at the stratum granulosum. This disruption is mediated by one of two Staphylococcus aureus exotoxins, exfoliative toxins A and B (ETA and ETB). Both ETA and ETB have been reported to be bacterial superantigens. A controversy exists, however, as other data indicate that these exotoxins are not superantigens. Here we demonstrate that recombinant exfoliative toxins produced in Escherichia coli do not act as T-cell mitogens and thus are not bacterial superantigens. These data fit the clinical profile of the disease, which is not associated with the classic symptoms of a superantigen-mediated syndrome.Staphylococcal scalded-skin syndrome (SSSS) is an exfoliative dermatitis of infants and children that results from infection with exfoliative-toxin-producing Staphylococcus aureus (1,15). SSSS is characterized by the formation of large bullae without inflammatory cell infiltrate and separation of extended areas of the epidermis at the stratum granulosum leaving the keratinocytes intact. Two biologically and serologically distinct S. aureus exotoxins are responsible for the skin manifestations of SSSS in humans, exfoliative toxin A (ETA) and exfoliative toxin B (ETB) (25). ETA (26.9 kDa) is encoded on the bacterial chromosome and shares 40% amino acid identity with the plasmid-borne ETB (27.3 kDa) (2, 13, 19). Despite extensive studies, the exact mechanism responsible for the skin disruption is not known.X-ray crystallographic structures of ETA and ETB (5,20,23,24) suggest that the toxins are members of the trypsin-like serine protease family. Protease activity has not been demonstrated for either toxin in vitro, but both ETA and ETB have intrinsic esterase activity, which is associated with serine proteases (3). Thus, it is likely that both toxins are proteases. In addition to having possible protease activity, both ETA and ETB are reported to be bacterial superantigens (14,16,17,24). Bacterial superantigens are a family of proteins able to bind simultaneously to the major histocompatibility complex and to the T-cell receptor (TCR), resulting in stimulation of a large number of T cells expressing specific V␤ subsets of the TCR repertoire (14).Previously, Fleischer and Bailey reported that recombinant ETA expressed in a superantigen-free S. aureus background does not have mitogenic activity (7). They conclude that the activity seen by others is due to contamination of the toxin preparations with other superantigens. However, since this report, additional literature has addressed the superantigenic activity of ETA and ETB. Here we demonstrate that recombinant exfoliative toxins produced in an Escherichia coli background do not act as T-cell mitogens and thus are not bacterial superantigens.Isolation, expression, and purification of recombinant exfoliative toxins. DNA fragments encoding ETA and ETB were obtained by utilizing PCR and DNA from exfoliative-toxinproducing bacterial strains. Toxins were expressed a...

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“…Another study showed that superantigenic effects were related to contamination of the commercial preparation used. 147,148 Other studies showed that ETs were able to produce a characteristic Vb signature; however, the amount of toxin needed to do this was substantially higher than with conventional SAgs. [149][150][151] Current evidence suggests that the superantigenic properties of ETs do not play an important role in the pathogenesis of SSSS; however, they may be important in other SAgmediated disorders.…”

Section: Cutaneous T-cell Lymphomamentioning

confidence: 98%

Superantigens in dermatology

Macias

Pereira

Rietkerk

et al. 2011

Journal of the American Academy of Dermatology

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Recombinant epidermolytic (exfoliative) toxin A of Staphylococcus aureus is not a superantigen

Cited by 31 publications

References 18 publications

A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C.

A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C.

RecombinantStaphylococcus aureusExfoliative Toxins Are Not Bacterial Superantigens

Superantigens in dermatology

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