The dwindling repertoire of antibiotics to treat Methicillin Resistant Staphylococcus aureus (MRSA) calls for novel treatment options. Quorum sensing inhibitors offer an alternative or an adjuvant to antibiotic therapy. Three novel biaryl hydroxyketone compounds were tested for efficacy in MRSA-infected animal models. Treatment of the compounds in an invasive murine MRSA kidney abscess model reduced the bacterial load on the kidneys by more than an order of magnitude. In a murine skin infection model the compounds promote wound healing and reduce the bacterial load on the wounds in combination with conventional antibiotics to which MRSA is resistant in mono therapy. This synergistic mode of action was also observed in vitro. For example, addition of 1µg/mL of these novel agents reduces the MIC of the ß-lactam antibiotic nafcillin from 60 to 1 µg/mL. These findings suggest that it might be possible to resurrect obsolete antibiotic therapy in combination with the newly discovered antivirulence agents.
