Abstract
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.
Highlights
Bis-(3′,5′)-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been shown to be a central regulator in bacterial physiology that reciprocally regulates behaviour of bacterial communities (D’Argenio and Miller, 2004; Jenal, 2004; Romling et al, 2005; Romling and Amikam, 2006)
Studies in a number of pathogenic bacteria have demonstrated the reciprocal relationship of diguanylate cyclases (DGCs) and PDE activities including those in Vibrio cholerae (Tamayo et al 2005; Tischler and Camilli, 2005), Salmonella typhimurium (Simm et al, 2004; Romling, 2005; Simm et al, 2005; Kader et al 2006), Yersinia pestis (Kirillina et al, 2004; Bobrov et al, 2005) and Pseudomonas aeruginosa (Hickman et al, 2005; Hoffman et al, 2005; Kulasakara et al, 2006)
Role of c-di-GMP in biofilm formation is distinct from the RetS signalling pathway
Summary
Bis-(3′,5′)-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been shown to be a central regulator in bacterial physiology that reciprocally regulates behaviour of bacterial communities (D’Argenio and Miller, 2004; Jenal, 2004; Romling et al, 2005; Romling and Amikam, 2006). A rise in c-di-GMP levels results in an increase in expression of various factors necessary for the establishment and maintenance of biofilm communities, whereas decrease in the production of the cyclic dinucleotide or its cleavage usually leads to enhanced expression of virulence and motility factors. In this signalling cascade, a number of controls exist to ensure proper responses to the levels of cellular c-di-GMP including signal generation, signal degradation and signal recognition. Studies in a number of pathogenic bacteria have demonstrated the reciprocal relationship of DGC and PDE activities including those in Vibrio cholerae (Tamayo et al 2005; Tischler and Camilli, 2005), Salmonella typhimurium (Simm et al, 2004; Romling, 2005; Simm et al, 2005; Kader et al 2006), Yersinia pestis (Kirillina et al, 2004; Bobrov et al, 2005) and Pseudomonas aeruginosa (Hickman et al, 2005; Hoffman et al, 2005; Kulasakara et al, 2006)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
