Ubiquitous selection for mecA in community-associated MRSA across diverse chemical environments

Abstract

AbstractCommunity-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) is threatening public health as it spreads worldwide across diverse environments. Its genetic hallmark, themecAgene, confers resistance to many β-lactam antibiotics. Here, we show that, in addition,mecAprovides a broad selective advantage across diverse chemical environments. Competing fluorescently labelled wild-type andmecA-deleted CA-MRSA USA400 strains across ~57,000 compounds supplemented with subinhibitory levels of the β-lactam drug cefoxitin, we find thatmecAprovides a widespread advantage across β-lactam and non β-lactam antibiotics, non-antibiotic drugs and even diverse natural and synthetic compounds. This advantage depends on the presence of cefoxitin and is strongly associated with the compounds’ physicochemical properties, suggesting that it may be mediated by differential compounds permeability into the cell. Indeed,mecAprotects the bacteria against increased cell-envelope permeability under subinhibitory cefoxitin treatment. Our findings suggest that CA-MRSA success might be driven by a cell-envelope mediated selective advantage across diverse chemical compounds.