The ins and outs of cyclic di-GMP signaling in Vibrio cholerae

[Display omitted] •A plethora of c-di-GMP metabolizing enzymes impact cellular processes in Vibrio cholerae.•C-di-GMP receptors are diverse and target processes are controlled by different mechanisms.•A variety of external signals are integrated into c-di-GMP signaling circuitry.•Mechanisms and functions of new c-di-GMP receptors are yet to be determined. The second messenger nucleotide cyclic dimeric guanosine monophosphate (c-di-GMP) governs many cellular processes in the facultative human pathogen Vibrio cholerae. This organism copes with changing environmental conditions in aquatic environments and during transitions to and from human hosts. Modulation of c-di-GMP allows V. cholerae to shift between motile and sessile stages of life, thus allowing adaptation to stressors and environmental conditions during its transmission cycle. The V. cholerae genome encodes a large set of proteins predicted to degrade and produce c-di-GMP. A subset of these enzymes has been demonstrated to control cellular processes – particularly motility, biofilm formation, and virulence – through transcriptional, post-transcriptional, and translational mechanisms. Recent studies have identified and characterized enzymes that modulate or sense c-di-GMP levels and have led towards mechanistic understanding of c-di-GMP regulatory circuits in V. cholerae.