Cyclic di-GMP as an Intracellular Signal Regulating Bacterial Biofilm Formation

Cyclic di-GMP is a novel second messenger in bacteria that was first described as an allosteric activator of cellulose synthase in Gluconacetobacter xylinus. It is now established that this nucleotide regulates a range of functions including developmental transitions, aggregative behavior, adhesion, biofilm formation and virulence in diverse bacteria. The level of cyclic di-GMP in bacterial cells is influenced by both synthesis and degradation. The GGDEF protein domain synthesizes cyclic di-GMP, whereas EAL and HD-GYP domains are involved in cyclic di-GMP hydrolysis. Bacterial genomes encode a number of proteins with GGDEF, EAL and HD-GYP domains. The majority of these proteins contain additional signal input domains, suggesting that their activities are responsive to environmental cues. An emerging theme is that high cellular levels of cyclic di-GMP promote biofilm formation and aggregative behavior whereas low cellular levels promote motility. The mechanism(s) by which cyclic di-GMP exerts its effects on these cellular functions is however poorly understood.