S. aureus can produce a wide range of virulence factors. Superantigenic toxins are responsible for a pro-inflammatory response during staphylococcal toxic shock syndrome (STSS) and are suspected to be involved in the process of S. aureus septic shock. These molecules bypass the normal antigen presentation by cross-linking the major histocompatibility complex class II molecules of antigen-presentating cells to the Vbeta domain of the T-cell receptor. By this way, each superantigenic toxin selectively stimulates and expands one or several Vbeta subsets producing a Vbeta signature.
We firstly showed in patients with menstrual and non-menstrual STSS due to the production of TSST-1 or SEB, that the Vbeta signature of the toxin could be detected in the Vbeta repertoire of patients at the early stage of the disease. Secondly, during S. aureus bacteremia, the prevalence of the gene encoding SEA was higher when septic shock occurred and the major meticillin-resistant S. aureus (MRSA) clone in France, named “clone Lyon” harbored this gene. in vitro, SEA induced a strong pro-inflammatory response that may enhanced the pro-inflammatory cascade during septic shock. However, the Vbeta signature of SEA has not been detected in patients with S. aureus (including MRSA) septic shock infected with a stain that produced SEA in vitro. Finally, in an animal model of sepsis, Lyon clone MRSA isolates induced a higher rate of mortality than meticillin-susceptible isolates, but this was not directly attributable to SEA.
The detection of a production of superantigenic toxins in vivo may lead to an early diagnosis of STSS and may facilitate the introduction of anti-toxinic agents that may improve the prognosis. The involvement of superantigenic toxins and especially SEA, in the pathophysiology of S. aureus septic shock remained uncertain.