Prophage-encoded methyltransferase drives adaptation of community-acquired methicillin-resistantStaphylococcus aureus

Abstract

AbstractWe recently described the evolution of a community-acquired methicillin-resistantStaphylococcus aureus(CA-MRSA) USA300 variant responsible for an outbreak of skin and soft tissue infections. Acquisition of a mosaic version of the Φ11 prophage (mΦ11) that increases skin abscess size was an early step in CA-MRSA adaptation that primed the successful spread of the clone. The present report shows how prophage mΦ11 exerts its effect on virulence for skin infection without encoding a known toxin or fitness genes. Abscess size and skin inflammation were associated with DNA methylase activity of an mΦ11-encoded adenine methyltransferase (designatedpamA).pamAincreased expression of fibronectin-binding protein A (fnbA; FnBPA), and inactivation offnbAeliminated the effect ofpamAon abscess virulence without affecting strains lackingpamA. Thus,fnbAis apamA-specific virulence factor. Mechanistically,pamAwas shown to promote biofilm formation in vivo in skin abscesses, a phenotype linked to FnBPA’s role in biofilm formation. Collectively, these data reveal a novel mechanism—epigenetic regulation of staphylococcal gene expression—by which phage can regulate virulence to drive adaptive leaps byS. aureus.Graphical Abstract