c-di-GMP and its Effects on Biofilm Formation and Dispersion: a Pseudomonas Aeruginosa Review

Abstract

Since its initial discovery as an allosteric factor regulating cellulose biosynthesis in Gluconacetobacter xylinus, the list of functional outputs regulated by c-di-GMP has grown. We have focused this article on one of these c-di-GMP-regulated processes, namely, biofilm formation in the organism Pseudomonas aeruginosa. The majority of diguanylate cyclases and phosphodiesterases encoded in the P. aeruginosa genome still remain uncharacterized; thus, there is still a great deal to be learned about the link between c-di-GMP and biofilm formation in this microbe. In particular, while a number of c-di-GMP metabolizing enzymes have been identified that participate in reversible and irreversible attachment and biofilm maturation, there is a still a significant knowledge gap regarding the c-di-GMP output systems in this organism. Even for the well-characterized Pel system, where c-di-GMP-mediated transcriptional regulation is now well documented, how binding of c-di-GMP by PelD stimulates Pel production is not understood in any detail. Similarly, c-di-GMP-mediated control of swimming, swarming and twitching also remains to be elucidated. Thus, despite terrific advances in our understanding of P. aeruginosa biofilm formation and the role of c-di-GMP in this process since the last version of this book (indeed there was no chapter on c-di-GMP!) there is still much to learn.

Figure 1. c-d-GMP: A central regulator of biofilms

Shown is the structure of c-di-GMP (center). This molecule is synthesized from two molecules of GTP by enzymes known as diguanylate cyclases (DGC), which carry a conserved GGDEF domain. c-di-GMP can be degraded by two families of phosphodiesterases (PDE); those with an EAL domain linearize the molecule to produce pGpG, and proteins with an HD-GYP domain generates 2 molecules of GMP from the signal. Illustration ©2014 William Scavone, Kestrel Studio, reprinted with permission.

Figure 2. A model for biofilm formation and dispersion in Pseudomonas aeruginosa

The steps of biofilm formation, as described in this chapter are: (1) Reversible attachment, likely via the flagellar pole; (2) Irreversible attachment via the long axis of the cell, resulting in a monolayer of cells; (3) microcolony formation; (4) macrocolony formation; and (5) dispersion. See the text for more detailed explanations of each step, which is based largely on laboratory studies. Illustration ©2014 William Scavone, Kestrel Studio, reprinted with permission.