Ligand-receptor recognition for activation of quorum sensing in Staphylococcus aureus

The accessory gene regulator (agr) locus controls many of the virulence toxins involved in Staphylococcus aureus pathogenesis, and can be divided into four specificity groups. AgrC is the only group-specific receptor to mediate both intra-group activation and inter-group inhibition. We studied the ligand-receptor recognition of the agr system in depth by using a luciferase reporter system to identify the key residues responsible for AgrC activation in two closely related agr groups, AgrC-I, and AgrC-IV. Fusion PCR and site-directed mutagenesis were used to screen for functional residues of AgrC. Our data suggest that for AgrC-IV activation, residue 101 is critical for activating the receptor. In contrast, the key residues for the activation of AgrC-I are located at residues 49 approximately 59, 107, and 116. However, three residue changes, T101A, V107S, I116S, are sufficient to convert the AIP recognizing specificity from AgrC-IV to AgrC-I.