The major Vibrio cholerae autoinducer and its role in virulence factor production

Cholera pathogen disarmed In a process called quorum sensing, certain bacteria can communicate with each other using chemical signalling molecules, allowing them to synchronize gene expression so that they act virtually as multicellular organisms. The cholera pathogen Vibrio cholerae uses quorum sensing to control virulence and to organize the biofilms that contribute to the difficulties of treating the infection. Now the major V. cholerae quorum-sensing signalling molecule, an autoinducer called CAI-1, has been identified and characterized as ( S )-3-hydroxytridecan-4-one, a molecule new to biology. Providing CAI-1 to the bacterium terminates the production of factors required for pathogenicity, suggesting a possible new treatment for this major pathogen. Vibrio cholerae , the causative agent of cholera, employs quorum sensing to repress virulence factor expression at high cell density. The nature of one of the major signals is now revealed as ( S )-3-hydroxytridecan-4-one constituting a new class of bacterial quorum sensing signalling molecules. Vibrio cholerae , the causative agent of the human disease cholera, uses cell-to-cell communication to control pathogenicity and biofilm formation 1 , 2 . 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 (2 S ,4 S )-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran borate 3 . 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.