Metabolism of cyclic-di-GMP in bacterial biofilms: From a general overview to biotechnological applications

Bacteria exist in nature in a planktonic single-cell state or in a sessile multicellular state, the biofilm. In the latter state, the bacterial community optimizes the cell-environment and cell-cell communication strategies. Biofilms are widely diffuse in many industrial, environmental and clinical settings and are less sensitive to treatments with antimicrobial agents compared to planktonic cells. Biofilms formed by bacterial pathogens, such as those formed by Pseudomonas aeruginosa in immunocompromised patients, have a high impact on public health. The switch between the planktonic and the biofilm lifestyle is strictly regulated by the second messenger 3', 5'-cyclic diguanylic acid (c-di-GMP). The intracellular levels of this molecule are controlled by two classes of enzymes: diguanylate cyclases (DGC) and phosphodiesterases (PDE). In this review we report the structural and functional data available to date on these enzymes and we summarize the possible medical, environmental and industrial biotechnological applications involving bacterial c-di-GMP metabolism.