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

TitleRole of the CAI-1 fatty acid tail in the Vibrio cholerae quorum sensing response.
Publication TypeJournal Article
Year of Publication2012
AuthorsPerez, LJ, Ng, W-L, Marano, P, Brook, K, Bassler, BL, Semmelhack, MF
JournalJ Med Chem
Volume55
Issue22
Pagination9669-81
Date Published2012 Nov 26
ISSN1520-4804
KeywordsBacterial Proteins, Cholera, Fatty Acids, Gene Expression Regulation, Bacterial, Ketones, Models, Molecular, Quorum Sensing, Vibrio cholerae
Abstract

<p>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.</p>

DOI10.1021/jm300908t
Alternate JournalJ. Med. Chem.
PubMed ID23092313
PubMed Central IDPMC3798069
Grant List5R01AI054442 / AI / NIAID NIH HHS / United States
GM082061 / GM / NIGMS NIH HHS / United States
K22 AI099087 / AI / NIAID NIH HHS / United States
R01 AI054442 / AI / NIAID NIH HHS / United States
R01 GM065859 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States