Bacillus cereus, an opportunistic human pathogen, can cause serious intestinal illnesses through the secretion of various toxins. The bacterium uses quorum sensing (QS) to regulate its gene expression in response to cell-population density, allowing it to effectively establish an infection. The inactivation of B. cereus’ QS could potentially provide an effective mode of lessening bacterial pathogenicity and decreasing its hemolytic activity. B. cereus utilizes a signal peptide, PapR, which binds to a virulence regulator PlcR. Through the synthesis of 7-mer PapR peptides (PapR7; ADLPFEF), we hope to find a peptide that outcompetes B. cereus’ native QS peptide, thus inhibiting QS. Previous work on this project yielded a collection of peptides, with modifications such as D-amino acids, some of which acted as inhibitors to PlcR. This collection is being expanded through the synthesis of select N-methyl derivatives and multiply substituted mutants which will be tested as inhibitors via bioassays.

Synthesis of PapR7 peptide analogs to inhibit quorum sensing in Bacillus cereus

ACS Spring 2022

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