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We combined mRNA display technology with lipid-nanodisc based selections and identified high-affinity ligands targeting the integral membrane sensor domain of the histidine kinase AgrC as potent inhibitors of Staphylococcus aureus quorum sensing-modulated virulence. Our study highlights the potential of this integrated approach for identifying functional modulators of integral membrane proteins.

Discovery of quorum quenchers targeting the membrane-embedded sensor domain of theStaphylococcus aureusreceptor histidine kinase, AgrC