Cyclic Di-GMP Signaling in Vibrio cholerae

The physiological role of cyclic di-GMP (c-di-GMP) in Vibrio cholerae has emerged from the analysis of phenotypes of mutants unable to produce GGDEF/EAL/HD-GYP proteins as well as from phenotypes of strains overproducing GGDEF/EAL/HD-GYP proteins. In V. cholerae, c-di-GMP is involved in the regulation of multiple cellular processes including biofilm formation, motility, and virulence. This chapter first introduces the processes regulated by c-di-GMP signaling, discusses what is currently known about the involvement of specific GGDEF/EAL/HD-GYP proteins in these processes, and then summarizes our current understanding of regulation of GGDEF/EAL/HD-GYP genes. In V. cholerae, similar to other organisms, c-di-GMP controls a motile-to-sessile lifestyle switch and negatively regulates motility. The importance of c-di-GMP in V. cholerae biology has been conclusively shown in studies involving VieA (VC1652). The VieA response regulator harbors an EAL domain and has phosphodiesterase (PDE) activity. A set of GGDEF/EAL/HD-GYP proteins produce a phenotype only when they are overproduced. Studies in other organisms have indicated that c-di- GMP can regulate motility at least at three different levels: transcriptional, posttranscriptional, and functional. cdgF overexpression also affected biofilm formation. Cells with increased c-di-GMP levels exhibited enhanced vps, vpsT, and vpsR expression and, consequently, formed thicker and more developed biofilms than those with wild-type levels of c-di-GMP. The role of Plz proteins in intestinal colonization was analyzed using an infant mouse colonization assay. Strains harboring a plzB deletion or a mutated version of the PilZ domain exhibited a decrease in colonization.