title: Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Anna D
authors.initials: AD
authors.lastname: Tischler
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D005838:Genotype; D006706:Homeostasis; D018613:Microscopy, Confocal; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D011135:Polysaccharides, Bacterial / Q000235:genetics; D012260:Ribonucleases; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development / Q000502:physiology*
chemical_list: D011135:Polysaccharides, Bacterial; C062025:bis(3',5')-cyclic diguanylic acid; D012260:Ribonucleases; D006152:Cyclic GMP