Population Analysis of Staphylococcus aureus Reveals a Cryptic, Highly Prevalent Superantigen SElW That Contributes to the Pathogenesis of Bacteremia

<jats:p> <jats:named-content content-type="genus-species">Staphylococcus aureus</jats:named-content> is an important human and animal pathogen associated with an array of diseases, including life-threatening necrotizing pneumonia and infective endocarditis. The success of <jats:named-content content-type="genus-species">S. aureus</jats:named-content> as a pathogen has been linked in part to its ability to manipulate the host immune response through the secretion of toxins and immune evasion molecules. The staphylococcal superantigens (SAgs) have been studied for decades, but their role in <jats:named-content content-type="genus-species">S. aureus</jats:named-content> pathogenesis is not well understood, and an appreciation for how SAgs manipulate the host immune response to promote infection may be crucial for the development of novel intervention strategies. Here, we characterized a widely prevalent, previously cryptic, staphylococcal SAg, SElW, that contributes to the severity of <jats:named-content content-type="genus-species">S. aureus</jats:named-content> infections caused by an important epidemic clone of <jats:named-content content-type="genus-species">S. aureus</jats:named-content> CC398. Our findings add to the understanding of staphylococcal SAg diversity and function and provide new insights into the capacity of <jats:named-content content-type="genus-species">S. aureus</jats:named-content> to cause disease. </jats:p>