Superantigens promote Staphylococcus aureus bloodstream infection by eliciting pathogenic interferon-gamma production

Significance Since their discovery over 30 y ago, it has become clear that the superantigens (SAgs) are important virulence factors produced during severe Staphylococcus aureus –mediated disease including bacteremia. However, until the current study, it was unclear how these toxins manipulated the immune system to promote infection. Here, we have demonstrated that the SAgs can target a critical immune signaling molecule (interferon gamma), inducing overproduction that promotes bacterial survival by subverting the ability of macrophages to be able to kill the pathogen. This highlights SAg activity as a critical target for antistaphylococcal therapy to mitigate the impact of severe S. aureus disease.