The expanding roles of c-di-GMP in the biosynthesis of exopolysaccharides and secondary metabolites

The cyclic dinucleotide c-di-GMP has emerged in the last decade as a prevalent intracellular messenger that orchestrates the transition between the motile and sessile lifestyles of many bacterial species. The motile-to-sessile transition is often associated with the formation of extracellular matrix-encased biofilm, an organized community of bacterial cells that often contributes to antibiotic resistance and host-pathogen interaction. It is increasingly clear that c-di-GMP controls motility, biofilm formation and bacterial pathogenicity partially through regulating the production of exopolysaccharides (EPS) and small-molecule secondary metabolites. This review summarizes our current understanding of the regulation of EPS biosynthesis by c-di-GMP in a diversity of bacterial species and highlights the emerging role of c-di-GMP in the biosynthesis of small-molecule secondary metabolites.