Regulation of Cyclic di-GMP Signaling in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is found ubiquitously throughout the environment, and it readily adapts to survive in different environments. Genome analysis reveals P. aeruginosa has a proportionally high number of transcriptional regulators and two-component systems, and it has become a model for studying bacterial gene regulation. Furthermore, P. aeruginosa is an opportunistic pathogen, establishing infections that are often difficult to treat, due to its recalcitrance to antimicrobials and host immune factors. This tolerance can be attributed to its ability to form protective communities known as biofilms. The transition from a planktonic to biofilm lifestyle is complex, and many regulatory pathways are involved. The secondary messenger molecule, cyclic di-GMP, regulates many factors involved in this process, including type IV pili, flagella, and exopolysaccharides. Thus, understanding how P. aeruginosa modulates cyclic di-GMP levels has important implications for P. aeruginosa virulence and environmental lifestyle. P. aeruginosa encodes 38 proteins predicted to be involved in cyclic di-GMP metabolism, indicating intricate regulatory mechanisms are in place to control intracellular cyclic di-GMP levels in response to various stimuli. While the role and regulation of many of these proteins remains unknown, this chapter will review currently identified cyclic di-GMP regulatory mechanisms in P. aeruginosa, including the Wsp, Gac, and Roc networks.