Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation

Mol Microbiol. 2004 Aug;53(3):857-69. doi: 10.1111/j.1365-2958.2004.04155.x.


While studying virulence gene regulation in Vibrio cholerae during infection of the host small intestine, we identified VieA as a two-component response regulator that contributes to activating expression of cholera toxin. Here we report that VieA represses transcription of Vibrio exopolysaccharide synthesis (vps) genes involved in biofilm formation by a mechanism independent of its phosphorelay and DNA-binding activities. VieA controls the intracellular concentration of the cyclic nucleotide second messenger cyclic diguanylate (c-di-GMP) using an EAL domain that functions as a c-di-GMP phosphodiesterase. Two-dimensional thin layer chromatography of nucleotide extracts confirmed that VieA reduces the concentration of c-di-GMP, opposing the action of c-di-GMP synthetase proteins. Expression of unrelated V. cholerae c-di-GMP synthetase or phosphodiesterae proteins also modulated c-di-GMP concentration and vps gene expression. We propose that c-di-GMP synthetase and phosphodiesterase domain-containing proteins contribute to regulating biofilm formation by controlling c-di-GMP concentration.

Publication types

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

MeSH terms

  • Biofilms / growth & development*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / physiology*
  • Escherichia coli / genetics
  • Gene Expression Regulation, Bacterial / genetics
  • Genotype
  • Homeostasis
  • Microscopy, Confocal
  • Phenotype
  • Plasmids / genetics
  • Polysaccharides, Bacterial / genetics
  • Ribonucleases
  • Vibrio cholerae / genetics
  • Vibrio cholerae / growth & development
  • Vibrio cholerae / physiology*


  • Polysaccharides, Bacterial
  • bis(3',5')-cyclic diguanylic acid
  • Ribonucleases
  • Cyclic GMP