cdiGMP

Cyclic di-GMP, often abbreviated c-di-GMP, is a ubiquitous second messenger in bacteria. It is a small cyclic dinucleotide that regulates numerous cellular processes, most notably the transition between motile and sessile lifestyles and the formation of biofilms. c-di-GMP levels are determined by synthesis and degradation via specialized enzymes.

Synthesis by diguanylate cyclases (DGCs) containing GGDEF domains converts two GTP molecules into c-di-GMP; degradation by phosphodiesterases (PDEs) containing EAL or HD-GYP domains converts c-di-GMP to pGpG or GMP. Bacteria often have many DGCs and PDEs, enabling complex, localized signaling networks.

c-di-GMP exerts its effects by binding to various effectors, including PilZ domain proteins, transcription factors, riboswitches, and enzymes involved in exopolysaccharide production and motility machinery. High intracellular c-di-GMP typically promotes biofilm formation and extracellular matrix production, while low levels favor motility and dispersal. The outcome is context-dependent.

Because c-di-GMP networks are highly modular and species-specific, bacteria coordinate diverse responses to environmental cues such as nutrient availability, surface contact, and stress. Localized signaling and cross-regulation among DGCs and PDEs can generate microdomains of c-di-GMP within cells.

In research, c-di-GMP is measured by liquid chromatography-tandem mass spectrometry, HPLC, or by fluorescence-based sensors and riboswitch reporters. Understanding c-di-GMP signaling has implications for combating biofilm-associated infections and for biotechnology applications that manipulate bacterial lifestyles.