c-di-GMP-mediated regulation of virulence and biofilm formation

Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9610, USA.
Current Opinion in Microbiology (Impact Factor: 5.9). 03/2007; 10(1):17-23. DOI: 10.1016/j.mib.2006.12.006
Source: PubMed


It is now apparent that the signaling molecule 3',5'-cyclic diguanylic acid (c-di-GMP) is a central regulator of the prokaryote biofilm lifestyle and recent evidence also links this molecule to virulence. Environmentally responsive signal transduction systems that control expression and/or activity of the enzymes (GGDEF and EAL domain containing proteins) that are responsible for synthesis and degradation of c-di-GMP have recently been identified. Members of the phosphorelay family feature prominently amongst these systems, which include several with hybrid polydomain sensors and one that is similar to well-characterized chemotaxis-controlling pathways. These findings support the hypothesis that c-di-GMP levels are tightly controlled in response to a broad range, in terms of both diversity and intensity, of extracellular signals. Insight into how c-di-GMP affects changes in gene expression and/or protein activity has come from the demonstration that proteins containing the PilZ domain can bind c-di-GMP and control phenotypes involved in biofilm formation and virulence. These recent developments should pave the way for researchers to answer the important question of how a vast array of extracellular signals that are sensed by multiple sensory transduction pathways which all lead to the production or destruction of c-di-GMP are coordinated such that the appropriate phenotypic response is produced.

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    • "AdrA is a diguanylate cyclase that synthesizes the second messenger signaling molecule bis-(3'-5')- cyclic dimeric guanosine monophosphate (cyclic-di-GMP), the effector molecule that binds to and allosterically activates cellulose synthase (Simm et al., 2004). c-di-GMP is widespread throughout the bacterial domain and plays a vital role in regulating the transition between the motile planktonic lifestyle and the sessile biofilm forming state (Cotter and Stibitz, 2007; Ahmad et al., 2011; Le Guyon et al., 2014). GGDEF and EAL domain proteins, acting as phosphodiesterases, are involved in turnover of this secondary messenger and play a determinative role in the expression level of multicellular behavior in S. Typhimurium (Simm et al., 2007). "
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    ABSTRACT: The ability of various microorganisms to attach to surfaces and create biofilms on them is rather a cause of concern for many industries, including for those occupied with food production and processing. Thus, the attachment of bacterial pathogens to food processing equipment is considered as an essential contributing factor in foodborne disease outbreaks, since this may ultimately lead to the contamination of food products. Improperly cleaned surfaces promote soil build-up, and, in the presence of water, contribute to the development of microbial biofilms which may contain pathogenic bacteria, such as Salmonella. It is well recognized that biofilm cells differ physiologically from their planktonic counterparts, presenting a modified and heterogeneous gene expression profile. Additionally, it has been observed that the resistance of sessile cells to antimicrobials and other environmental stresses is significantly increased compared to what is normally seen with the same cells being planktonic. Noteworthily, salmonellae have been shown to survive for years in non-enteric habitats, including sessile communities on food contact and product surfaces. Indeed, several reports have demonstrated the ability of Salmonella to attach and form biofilms on abiotic surfaces, such as stainless steel, plastic, rubber, glass, marble and cement. Salmonella is also able to strongly attach and persist on both animal and plant (produce) surfaces. It is believed that the attachment to all these surfaces and the subsequent biofilm formation on them enhance the capacity of pathogenic Salmonella bacteria to successfully cope with hurdles that are commonly encountered outside the host and within food processing. The purpose of this chapter is to review the current available Efstathios Giaouris and Live L. Nesse 2 knowledge related to the attachment of Salmonella to food contact and product surfaces and the possible subsequent sessile development on them in view of the strong impact of these two interrelated capabilities on the enhancement of its survival outside the host, its environmental persistence and spread. Undoubtedly, the ability to recognize why and how Salmonella attach to such surfaces is an important area of focus, since this may provide valuable ways towards the elimination of this important pathogen from food processing environments and eventually lead to reduced Salmonella-associated human illness.
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    • "Published by John Wiley & Sons Ltd. All rights reserved the expression of virulence genes, chemotaxis responses, bacterial motility, secretary system, biofilm formation, and many other functions (Simm et al., 2004; Cotter & Stibitz, 2007; Tamayo et al., 2007; Hengge, 2009). "
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    • "High levels of c-di-GMP promoting sessile growth, while low levels correlate with planktonic existence (Gjermansen et al., 2005; Thormann et al., 2006; Cotter and Stibitz, 2007; Barraud et al., 2009; Basu Roy et al., 2012). Levels of c-di-GMP are enzymatically modulated by diguanylate cyclases (DGC), proteins containing a GGDEF domain, and phosphodiesterases (PDE) harbouring either an EAL or HD-GYP domain (Cotter and Stibitz, 2007; Schirmer and Jenal, 2009). In P. putida, two genes (PP0164, PP0165), encoding a putative periplasmic protein and a putative transmembrane protein involved in c-di-GMP modulation, were found to be required for biofilm formation and starvation-induced dispersion, with mutants in PP0164 being unable to disperse from biofilms in response to carbon starvation (Gjermansen et al., 2005). "
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    ABSTRACT: Dispersion enables the transition from the biofilm to the planktonic growth state in response to various cues. While several P. aeruginosa proteins, including BdlA and the c-di-GMP phosphodiesterases DipA, RbdA, and NbdA, have been shown to be required for dispersion to occur, little is known about dispersion cue sensing and the signaling translating these cues into the modulation c-di-GMP levels to enable dispersion. Using glutamate-induced dispersion as a model, we report that dispersion-inducing nutrient cues are sensed via an outside-in signaling mechanism by the diguanylate cyclase NicD belonging to a family of seven transmembrane (7TM) receptors. NicD directly interacts with BdlA and the phosphodiesterase DipA, with NicD, BdlA, and DipA being part of the same pathway required for dispersion. Glutamate-sensing by NicD results in NicD dephosphorylation and increased cyclase activity. Active NicD contributes to the non-processive proteolysis and activation of BdlA via phosphorylation and temporarily elevated c-di-GMP levels. BdlA, in turn, activates DipA, resulting in the overall reduction of c-di-GMP levels. Our results provide a basis for understanding the signaling mechanism based on NicD to induce biofilm dispersion that may be applicable to various biofilm-forming species and may have implications for the control of biofilm-related infections.
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