Characterization of Human Type C Enterotoxin Produced by Clinical S. epidermidis Isolates

Staphylococcal Enterotoxins (SEs) are superantigens (SAg) originally produced by S. aureus, but their presence in coagulase negative staphylococci (CNS) has long been suspected. This study aims to better characterize a novel C-like enterotoxin expressed by clinical S. epidermidis strains, called SEC(epi). We isolated and characterized SEC(epi) for its molecular and functional properties. The toxin was structurally modeled according to its significant similarity with S. aureus SEC3. Most of SEC amino acid residues important for the formation of the trimolecular Major Histocompatibility Complex II MHCII–SEC–T Cell Receptor TCR complex are conserved in SEC(epi). The functional properties of SEC(epi) were estimated after cloning, expression in E. coli, and purification. The recombinant SEC(epi) toxin exhibits biological characteristics of a SAg including stimulation of human T-cell mitogenicity, inducing and releasing high cytokines levels: IL-2, -4, -6, -8, -10, IFN-γ, TNF-α and GM-CSF at a dose as low as 3.7 pM. Compared to SEC(aureus), the production of pro-sepsis cytokine IL-6 is significantly higher with SEC(epi)-activated lymphocytes. Furthermore, SEC(epi) is stable to heat, pepsin or trypsin hydrolysis. The SEC(epi) superantigen produced by CNS is functionally very close to that of S. aureus, possibly inducing a systemic inflammatory response at least comparable to that of SEC(aureus), and may account for S. epidermidis pathogenicity.