Cyclic Dimeric GMP Signaling and Regulation of Surface-Associated Developmental Programs

Abstract

Cyclic dimeric GMP (c-di-GMP) has emerged as a ubiquitous second messenger in bacteria that controls the transition from the free-living, motile lifestyle to the biofilm lifestyle (5, 12, 19). Production and degradation of c-di-GMP are controlled by proteins containing the GGDEF and EAL or HD-GYP domains, respectively. The GGDEF domain harbors intrinsic diguanylate cyclase (DGC) activity, and the EAL or HD-GYP domain has c-di-GMP phosphodiesterase (PDE) activity (4, 21-23). c-di-GMP was initially identified in Gluconacetobacter xylinus as an allosteric activator of cellulose synthase (20). Recent studies have shown that c-di-GMP modulates cell differentiation, biofilm formation, motility, and virulence in a diverse group of microorganisms (5, 12, 19). Our understanding of the biological processes and target molecules controlled by c-di-GMP signaling is increasing. However, at present, we have a limited understanding of the mechanisms through which c-di-GMP affects biofilm formation, mechanisms by which the activity of GGDEF/EAL proteins are regulated, and how multiple GGDEF and EAL domain proteins contribute to cellular c-di-GMP levels. In this issue, a new study by Ferreira et al. (8) is beginning to shed light on these questions in Vibrio parahaemolyticus, a facultative human pathogen responsible for the most common Vibrio-associated, seafood-borne gastroenteritis.