TY - JOUR
T1 - The major Vibrio cholerae autoinducer and its role in virulence factor production
AU - Higgins, Douglas A.
AU - Pomianek, Megan E.
AU - Kraml, Christina M.
AU - Taylor, Ronald K.
AU - Semmelhack, Martin F.
AU - Bassler, Bonnie L.
N1 - Funding Information:
Acknowledgements We thank members of the Bassler, Semmelhack and Hughson groups for discussions. We thank I. Pelczer for the double-quantum filtered correlation spectroscopy experiment and initial 13C-NMR studies. This work was supported by the Howard Hughes Medical Institute (B.L.B.) and grants from the National Science Foundation (B.L.B.) and the National Institutes of Health (B.L.B. and M.F.S.). M.E.P. was supported by a graduate fellowship from Amgen through the Medicinal Chemistry Division of the American Chemical Society and by the Horst Witzel Prize from the Cephalon Corporation.
PY - 2007/12/6
Y1 - 2007/12/6
N2 - 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.
AB - 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.
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U2 - 10.1038/nature06284
DO - 10.1038/nature06284
M3 - Article
C2 - 18004304
AN - SCOPUS:36849039449
SN - 0028-0836
VL - 450
SP - 883
EP - 886
JO - Nature
JF - Nature
IS - 7171
ER -