Invited
Modulating bacterial quorum sensing system with peptidic analogues

The quorum sensing system of Bacillus cereus, an opportunistic human pathogen, utilizes by the autoinducing PapR peptide signal to mediate the activation of the pleiotropic virulence regulator PlcR. A set of synthetic 7‑mer PapR-derived peptides (PapR₇; ADLPFEF) have been shown to inhibit very effiecntly the PlcR regulon activity and the production of virulence factors, reflected by a loss in hemolytic activity without affecting bacterial growth. Interestingly, these first potent synthetic inhibitors involved D-amino acids or alanine replacements at three amino acids; proline (P) glutamic (E) and phenylalanine (F) of the heptapeptide PapR. To better understand the role of these three crucial positions in PlcR activity, we presnet a second generation design, synthesis, and characterization of PapR₇-derived combinations, of double and triple alanine and D-amino acids replacement at these positions. Our findings generate a new set of non-native PapR₇-derived peptides that inhibit PlcR regulon activity and the production of virulnce factors. Using the amino acids subtitution strategy, we revealed the importance role of Glu6 to discriminate against other cell–cell signalling peptides. Moreover, we found the potential of D-Glutamic substitution at designing potent PlcR antagoinst. Our method might be applied to other quroum sensing system to design new anti-virulence agents.