A cyclic‐di‐GMP receptor required for bacterial exopolysaccharide production

Abstract

Summary: Bis‐(3′,5′)‐cyclic‐dimeric‐guanosine monophosphate (c‐di‐GMP) has been shown to be a global regulatory molecule that modulates the reciprocal responses of bacteria to activate either virulence pathways or biofilm formation. The mechanism of c‐di‐GMP signal transduction, including recognition of c‐di‐GMP and subsequent phenotypic regulation, remain largely uncharacterized. The key components of these regulatory pathways are the various adaptor proteins (c‐di‐GMP receptors). There is compelling evidence suggesting that, in addition to PilZ domains, there are other unidentified c‐di‐GMP receptors. Here we show that the PelD protein of Pseudomonas aeruginosa is a novel c‐di‐GMP receptor that mediates c‐di‐GMP regulation of PEL polysaccharide biosynthesis. Analysis of PelD orthologues identified a number of conserved residues that are required for c‐di‐GMP binding as well as synthesis of the PEL polysaccharide. Secondary structure similarities of PelD to the inhibitory site of diguanylate cyclase suggest that a common fold can act as a platform to bind c‐di‐GMP. The combination of a c‐di‐GMP binding site with a variety of output signalling motifs within one protein domain provides an explanation for the specificity for different cellular responses to this regulatory dinucleotide.