Biofilm control by interfering with c-di-GMP metabolism and signaling

Biofilm formation and biofilm-induced biodeterioration of surfaces have deeply affected the life of our community. Cyclic dimeric guanosine monophosphate (c-di-GMP) is a small nucleotide-based signaling molecule in bacteria, which functions as a second messenger mediating a wide range of bacterial processes, such as cell motility, biofilm formation, virulence expression, and cell cycle progression. C-di-GMP regulated phenotypes are triggered by a variety of determinants, such as metabolic cues and stress factors that affect c-di-GMP synthesis, the transduction and conducting of signals by specific effectors, and their actions on terminal targets. Therefore, understanding of the regulatory mechanisms of c-di-GMP would greatly benefit the control of the relevant bacterial processes, particularly for the development of anti-biofilm technologies. Here, we discuss the regulatory determinants of c-di-GMP signaling, identify the corresponding chemical inhibitors as anti-biofilm agents, and shed light on further perspectives in the metabolic regulation of c-di-GMP through chemical and biological approaches. This review will advance the development of anti-biofilm policies applied in the industries of medicine, environment and engineering.