Document Detail

The major Vibrio cholerae autoinducer and its role in virulence factor production.
MedLine Citation:
PMID:  18004304     Owner:  NLM     Status:  MEDLINE    
Vibrio cholerae, the causative agent of the human disease cholera, uses cell-to-cell communication to control pathogenicity and biofilm formation. This process, known as quorum sensing, relies on the secretion and detection of signalling molecules called autoinducers. At low cell density V. cholerae activates the expression of virulence factors and forms biofilms. At high cell density the accumulation of two quorum-sensing autoinducers represses these traits. These two autoinducers, cholerae autoinducer-1 (CAI-1) and autoinducer-2 (AI-2), function synergistically to control gene regulation, although CAI-1 is the stronger of the two signals. V. cholerae AI-2 is the furanosyl borate diester (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran borate. Here we describe the purification of CAI-1 and identify the molecule as (S)-3-hydroxytridecan-4-one, a new type of bacterial autoinducer. We provide a synthetic route to both the R and S isomers of CAI-1 as well as simple homologues, and we evaluate their relative activities. Synthetic (S)-3-hydroxytridecan-4-one functions as effectively as natural CAI-1 in repressing production of the canonical virulence factor TCP (toxin co-regulated pilus). These findings suggest that CAI-1 could be used as a therapy to prevent cholera infection and, furthermore, that strategies to manipulate bacterial quorum sensing hold promise in the clinical arena.
Douglas A Higgins; Megan E Pomianek; Christina M Kraml; Ronald K Taylor; Martin F Semmelhack; Bonnie L Bassler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-11-14
Journal Detail:
Title:  Nature     Volume:  450     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-07     Completed Date:  2008-01-11     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  883-6     Citation Subset:  IM    
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MeSH Terms
Colony Count, Microbial
Escherichia coli
Ketones / chemical synthesis,  chemistry,  isolation & purification*,  pharmacology*
Magnetic Resonance Spectroscopy
Models, Biological
Quorum Sensing*
Vibrio cholerae / cytology,  metabolism*,  pathogenicity*
Virulence Factors / biosynthesis*,  genetics
Grant Support
Reg. No./Substance:
0/(2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran borate; 0/3-hydroxytridecan-4-one; 0/Borates; 0/Furans; 0/Ketones; 0/Virulence Factors
Comment In:
Nature. 2007 Dec 6;450(7171):805-7   [PMID:  18063996 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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