A Small Molecule That Inhibits the Quorum Sensing Receptor AgrC in <i>Staphylococcus aureus</i>

We report the synthesis and characterization of a small molecule, CP-20, capable of inhibiting the key quorum sensing receptor AgrC in <i>Staphylococcus aureus</i>. Structural alterations enabled the discovery of a CP-20 derivative that is capable of complete quorum sensing inhibition with mid-nanomolar potency. <i>In vitro</i> biochemical investigations support CP-20 binding AgrC and competitively inhibiting its activity. CP-20 represents a versatile and synthetically tractable small molecule probe for investigating Staphylococcal virulence via quorum sensing modulation.