The importance of the PapR7 C-terminus and amide protons in mediating quorum sensing in Bacillus cereus

Michael Gorgan, Shahar Vanunu Ofri, Emilee R. Engler, Avishag Yehuda, Elizabeth Hutnick, Zvi Hayouka, Michael A. Bertucci

Research output: Contribution to journalArticlepeer-review

Abstract

The opportunistic human pathogen Bacillus cereus controls the expression of key infection-promoting phenotypes using bacterial quorum sensing (QS). QS signal transduction within the species is controlled by an autoinducing peptide, PapR7, and its cognate receptor, PlcR, indicating that the PlcR:PapR interface is a prime target for QS inhibitor development. The C-terminal region of the peptide (PapR7; ADLPFEF) has been successfully employed as a scaffold to develop potent QS modulators. Despite the noted importance of the C-terminal carboxylate and amide protons in crystallographic data, their role in QS activity has yet to be explored. In this study, an N-methyl scan of PapR7 was conducted in conjunction with a C-terminal modification of previously identified B. cereus QS inhibitors. The results indicate that the amide proton at Glu6 and the C-terminal carboxylate are important for effective QS inhibition of the PlcR regulon. Through β-galactosidase and hemolysis assays, a series of QS inhibitors were discovered, including several capable of inhibiting QS with nanomolar potency. These inhibitors, along with the structure–activity data reported, will serve as valuable tools for disrupting the B. cereus QS pathway towards developing novel anti-infective strategies.

Original languageAmerican English
Article number104139
JournalResearch in Microbiology
Volume174
Issue number8
DOIs
StatePublished - 1 Nov 2023

Keywords

  • Bacillus cereus group
  • Peptide structure–activity relationships
  • PlcR antagonists
  • Quorum sensing

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Microbiology

Fingerprint

Dive into the research topics of 'The importance of the PapR7 C-terminus and amide protons in mediating quorum sensing in Bacillus cereus'. Together they form a unique fingerprint.

Cite this