The Regulation of Alginate Biosynthesis via Cyclic di-GMP Signaling

Abstract

Bacterial alginates are anionic exopolysaccharides, which are produced by Pseudomonas and Azotobacter species. Bacterial cells embedded in extracellular polymeric substances such as alginates have a survival advantage as they are protected against various physical and chemical stresses as well as the immune system. In the model organism P. aeruginosa, alginate is polymerized and secreted by a multiprotein complex spanning the entire bacterial envelope. The ubiquitous second messenger cyclic di-GMP is required for activation of alginate production. In this chapter, after a brief overview on alginates, their general properties, biological functions and applications, we will discuss the importance of alginate production and its regulation via cyclic di-GMP signaling during bacterial pathogenesis, which implies biofilm formation coinciding with chronic infection. We will review the current understanding of the molecular pathways controlling the cyclic di-GMP-dependent regulation of alginate production including (1) diguanylate cyclases and phosphodiesterases, which control cellular levels of cyclic di-GMP, (2) the cyclic di-GMP receptor/effector protein Alg44 that senses cyclic di-GMP, while it interacts with other protein subunits to constitute the alginate biosynthesis/modification/secretion multiprotein complex at the bacterial envelope, (3) insights into structural elucidation of PilZ domain-containing Alg44 including mechanistic insights into cyclic di-GMP binding and activation of alginate polymerization, and (4) other regulator proteins whose functions are controlled by cyclic di-GMP levels and impact on alginate production.