The Major Vibrio Cholerae Autoinducer and Its Role in Virulence Factor Production

Nature. 2007 Dec 6;450(7171):883-6. doi: 10.1038/nature06284. Epub 2007 Nov 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biofilms
  • Borates
  • Colony Count, Microbial
  • Escherichia coli
  • Furans
  • Ketones / chemical synthesis
  • Ketones / chemistry
  • Ketones / isolation & purification*
  • Ketones / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Models, Biological
  • Quorum Sensing*
  • Vibrio cholerae / cytology
  • Vibrio cholerae / metabolism*
  • Vibrio cholerae / pathogenicity*
  • Virulence Factors / biosynthesis*
  • Virulence Factors / genetics

Substances

  • (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran borate
  • 3-hydroxytridecan-4-one
  • Borates
  • Furans
  • Ketones
  • Virulence Factors