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

Michael Gorgan1, Shahar Vanunu Ofri2, Emilee R Engler3

  • 1Department of Chemistry, Lafayette College, 701 Sullivan Rd., Easton, PA 18042, United States.

Research in Microbiology
|September 27, 2023
PubMed

Insights

Researchers identified key molecular features of Bacillus cereus quorum sensing (QS) inhibitors. Modifications to the PapR7 peptide revealed that the C-terminal carboxylate and amide protons are crucial for effective QS inhibition, leading to new anti-infective strategies.

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Bacillus cereus, an opportunistic pathogen, utilizes bacterial quorum sensing (QS) to regulate virulence factors.
  • The PlcR:PapR7 signaling pathway is central to B. cereus QS and represents a potential target for anti-infective therapies.
  • Previous QS inhibitor development focused on the C-terminal region of PapR7.

Purpose of the Study:

  • To investigate the role of C-terminal carboxylate and amide protons in PapR7-mediated QS activity.
  • To develop novel QS inhibitors targeting the PlcR:PapR7 interface.
  • To identify structure-activity relationships for B. cereus QS inhibitors.

Main Methods:

  • N-methyl scan of the PapR7 peptide.
  • C-terminal modification of existing B. cereus QS inhibitors.
  • β-galactosidase and hemolysis assays to assess QS inhibition.
  • Structure-activity relationship analysis.

Main Results:

  • The amide proton at Glu6 and the C-terminal carboxylate of PapR7 are critical for QS inhibition.
  • Several novel QS inhibitors were identified with nanomolar potency.
  • Structure-activity data provides insights into inhibitor design.

Conclusions:

  • The C-terminal modifications are essential for potent QS inhibition of the PlcR regulon in B. cereus.
  • Developed inhibitors and structure-activity data can guide the development of novel anti-infective strategies against B. cereus.
  • Targeting the PlcR:PapR7 interface offers a promising avenue for combating B. cereus infections.

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