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

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.

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