The signaling peptide PapR is required for the activity of the quorum-sensor PlcRa in .

The transcriptional regulator PlcR, its cognate cell-cell signaling heptapeptide PapR, and the oligopeptide permease OppABCDF, required for PapR import, form a quorum-sensing system that controls the expression of virulence factors in and species. In strain ATCC 14579, the transcriptional regulator PlcRa activates the expression of gene, which encodes an AbrB-like transcriptional regulator involved in cysteine biosynthesis. PlcRa is a structural homolog of PlcR: in particular, its C-terminal TPR peptide-binding domain could be similarly arranged as in PlcR. The signaling peptide of PlcRa is not known. As PlcRa is a PlcR-like protein, the cognate PapR peptide (ADLPFEF) is a relevant candidate to act as a signaling peptide for PlcRa activation. Also, the putative PapRa peptide (CSIPYEY), encoded by the gene adjacent to the gene, is a relevant candidate as addition of synthetic PapRa induces a dose-dependent increase of expression. To address the issue of peptide selectivity of PlcRa, the role of PapR and PapRa peptides in PlcRa activity was investigated in 407 strain, by genetic and functional complementation analyses. A transcriptional fusion between the promoter of and was used to monitor the PlcRa activity in various genetic backgrounds. We demonstrated that PapR was necessary and sufficient for PlcRa activity. We showed that synthetic PapRs from pherogroups II, III and IV and synthetic PapRa were able to trigger expression, suggesting that PlcRa is less selective than PlcR. Lastly, the mode of binding of PlcRa was addressed using an approach. Overall, we report a new role for PapR as a signaling peptide for PlcRa activity and show a functional link between PlcR and PlcRa regulons in .