diguanylate

Diguanylate, more commonly known as cyclic di-GMP (c-di-GMP), is a small molecule second messenger used by many bacteria to regulate switching between motile and sessile lifestyles. It is a cyclic dinucleotide composed of two guanosine monophosphate units linked to form a 3',5'-cyclic phosphate.

Biosynthesis and degradation of c-di-GMP are coordinated by specific enzymes. Diguanylate cyclases (DGCs) contain GGDEF domains and catalyze the condensation of two GTP molecules to form c-di-GMP, typically regulated by environmental cues and allosteric feedback mechanisms such as an I-site that binds c-di-GMP to inhibit activity. Degradation is carried out by phosphodiesterases (PDEs) with either EAL or HD-GH domains, which break c-di-GMP down to the linear dinucleotide pGpG and eventually to GMP. The balance of DGC and PDE activities determines the cellular level of c-di-GMP.

Function and mechanism of action arise from c-di-GMP binding to diverse effector proteins and riboswitches. Many effectors contain PilZ domains or other sensory outputs, translating c-di-GMP binding into changes in gene expression, exopolysaccharide production, adhesion, and cell motility. In bacteria, high intracellular c-di-GMP generally promotes biofilm formation and extracellular matrix production, whereas low levels favor motility and dispersal. Notable targets include cellulose synthase complexes and various adhesins; the outcome is often context-dependent and species-specific.

Distribution and significance: c-di-GMP is widely distributed among bacteria and is a central regulator of transition between planktonic and biofilm lifestyles. It is also a potential target for strategies to control biofilm-associated infections and industrial biofouling. Detection and study use methods such as liquid chromatography–mass spectrometry and various fluorescent or riboswitch-based biosensors.