Pharmacologic disruption of agr quorum sensing in Staphylococcus aureus promotes host defense against skin and soft tissue infections. Staphylococcus aureus

Drug discovery for novel anti-infectives is essential to meet the global health threat of antibiotic resistant bacterial infections, including those caused by Staphylococcus aureus1,2. Because ~90% of S. aureus infections involve skin and soft tissues (SSTIs)3,4, we hypothesized that developing anti-virulence therapeutics5,6 for SSTIs could minimize pressure on resistance development while sparing conventional antibiotics for control of systemic infections. We identified a small molecule inhibitor that disrupted signaling by a quorum sensing operon, agr, associated with human SSTIs7,8 without affecting agr-independent growth. Overall design: quorom sensing, wild type vs. agr mutant, savirin treatment