Role of the CAI-1 fatty acid tail in the Vibrio cholerae quorum sensing response

Lark J. Perez, Wai Leung Ng, Paul Marano, Karolina Brook, Bonnie L. Bassler, Martin F. Semmelhack

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Quorum sensing is a mechanism of chemical communication among bacteria that enables collective behaviors. In V. cholerae, the etiological agent of the disease cholera, quorum sensing controls group behaviors including virulence factor production and biofilm formation. The major V. cholerae quorum-sensing system consists of the extracellular signal molecule called CAI-1 and its cognate membrane bound receptor called CqsS. Here, the ligand binding activity of CqsS is probed with structural analogues of the natural signal. Enabled by our discovery of a structurally simplified analogue of CAI-1, we prepared and analyzed a focused library. The molecules were designed to probe the effects of conformational and structural changes along the length of the fatty acid tail of CAI-1. Our results, combined with pharmacophore modeling, suggest a molecular basis for signal molecule recognition and receptor fidelity with respect to the fatty acid tail portion of CAI-1. These efforts provide novel probes to enhance discovery of antivirulence agents for the treatment of V. cholerae.

Original languageEnglish (US)
Pages (from-to)9669-9681
Number of pages13
JournalJournal of Medicinal Chemistry
Volume55
Issue number22
DOIs
StatePublished - Nov 26 2012

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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