TURNING OFF BACILLUS CEREUS QUORUM SENSING SYSTEM PLCR:PAPR BY PEPTIDIC ANALOGS

Bacterial cell-cell communication, termed quorum sensing (QS), regulates important adaptive activities such virulence, antibiotic production, sporulation and competence, according to population densities. Developing methods to manipulate bacterial quorum sensing systems have attracted significant interest as a potential strategy for attenuating infection.

Bacillus cereus, an opportunistic human pathogen which is a member of the Gram-positive B-bacilli group that includes Bacillus thuringiensis, an insect pathogen, and Bacillus anthracis, utilizes autoinducing PapR peptide signals to mediate QS by activating pleiotropic virulence regulator PlcR¹.

As the blockade of quorum sensing offers a novel strategy for attenuating bacteria pathogenic functions, we studied the structure and molecular activity of the PlcR – PapR QS system in B. cereus. Based on biochemical and structural findings, we designed, synthesized and characterized direct QS synthetic PapR 7-mer (PapR₇) derived peptides to determine the functionally critical residues within PlcR – PapR₇ interactions. Our finding reveals a set of non-native peptides that can inhibit PlcR regulon activity with micromolar IC₅₀ values and block this cell-cell communication system. Moreover, we demonstrated that the inhibition is mediated by quorum sensing and regulation of PlcR expression, and does not affect bacterial growth. These peptides represent, to our knowledge, is the first reported potent synthetic inhibitors of QS in B. cereus and could potentially be used as novel antimicrobial compounds.

¹Slamti, L., & Lereclus, D. (2002). A cell–cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group. The EMBO journal, 21(17), 4550-4559.‏