Seminars

Community-associated methicillin-resistant Staphylococcusaureus (CA-MRSA) has spread worldwide and is threatening public health. Itshallmark is the mecA gene, whichconfers resistance to nearly all β-lactam antibiotics. However, it is unknownwhether mecA provides additionalselective advantages or disadvantages across other chemical environments. In myseminar, I will present a new competition-based assay that we’ve developed todetermine the fitness effect of mecA.In the assay, we compete between differentially fluorescently-labeled wild-typeCA-MRSA and a mecA deleted strain in1536-well plates in the presence of ~57,000 diverse chemical compounds and cefoxitin,a β-lactam, at a sub-inhibitory concentration. Surprisingly, and in contrast toother resistant mechanisms, we find that mecAprovides a ubiquitous advantage in diverse chemical environments, includingantibiotics, non-antibiotic therapeutic drugs and even natural products andsynthetic compounds. I will share our findings as well as our insights for themechanism underlying this advantage. Overall, our findings suggest a wide basisto explain CA-MRSA remarkable success and rapid dissemination worldwide.