Preliminary assessment of the therapeutic potential of staphylococcal enterotoxin-like W via biological activity and TCR binding sites analysis.

Staphylococcal enterotoxin-like W (SElW) is a novel, widely prevalent enterotoxin-like protein that functions as a classical staphylococcal superantigen (SAg) and has been shown to exacerbate infections caused by the S. aureus epidemic clone CC398. However, the genetic distribution and amino acid polymorphisms, biological and antitumor activity, and T cell receptor (TCR) binding sites of SElW in S. aureus strains prevalent in China have not been investigated. The carrier rate and distribution of selw were determined by PCR, the stability and antitumor activity of recombinant SElW (rSElW) protein were evaluated. The superantigen activity of the five mutants (Y18A, N19A, W55A, C88A, and C98A) was compared to that of wild-type SElW (WT-rSElW) to assess the role of these sites in mediating TCR binding. The selw gene was detected in all (986/986, 100%) dominant clonal lineages of S. aureus and most strains (69.1%, 56/81) had a full-length selw open reading frame with a sequence identity of 90.5%. rSElW was heat-stable but not resistant to pepsin and trypsin digestion. Additionally, rSElW significantly inhibited the proliferation of MCF-7 and AGS, but not A549 in vitro. The rSElW mutants C88A and C98A markedly reduced T cell proliferation and IL-2, IFN-γ and TNF-α secretion compared to WT-rSElW. rSElW is a highly prevalent SAg that binds to the TCR via C98 and C88, which may serve as novel therapeutic targets for S. aureus infections and its application in anti-tumor activity needs to be further evaluated in vivo.