Does β-toxin Production Contribute to the Cytotoxicity of Hypervirulent Staphylococcus aureus?

TO THE EDITOR—The recent article by Salgado-Pabón et al, which reported that excision of the staphylococcal β-toxin– converting bacteriophage wSa3 is common in wSa3-positive strains, was interesting [1]. By demonstrating that β-toxin production is selected for by in vivo infection and enhances virulence in rabbit models of pneumonia and infective endocarditis, Salgado-Pabón et al identified a previously unsuspected role for β-toxin in wSa3-positive Staphylococcus aureus. Regarding infective endocarditis, they insightfully predicted that the increase in vegetation size associated with β-toxin production could be linked to its nucleoprotein ligase activity. However, other mechanisms by which β-toxin could contribute to pathogenesis in these models were not discussed. Interestingly, β-toxin has been shown to participate in the intracellular virulence of S. aureus [2]. β-toxin production, along with production of phenol-soluble modulins, is reportedly required for the disruption of phagosomal membranes by S. aureus after internalization and for the bacterium to gain access to the cytoplasm of the infected cell, eventually triggering cell death. Interestingly, hypervirulent strains such as S. aureusUSA300 escape phagosomes and are highly cytotoxic despite harboring wSa3 [3]. Facing this apparent contradiction, some authors hypothesized that intraphagosomal oxidative stress induces wSa3 excision and restores β-toxin production [4]. The finding that wSa3 excision is common during in vivo infection adds credibility to this hypothesis, which we have investigated recently. We used the hemolysis profile analysis on sheep blood agar plates described by Salgado-Pabón et al to quantify the frequency of β-toxin variants in S. aureus populations. Functional β-toxin production was confirmed using a CAMP test,