Chapter 19 : Environmental Control of Cyclic Di-GMP Signaling in : from Signal to Output

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Recently it was shown that P concentration regulates biofilm formation by Pf0-1 through a cyclic di-GMP (c-di-GMP) signaling pathway. Study of this response has produced one of the more complete pictures of how c-di-GMP signaling can link an environmental signal to a complex biological output. This research supports the idea that c-di-GMP is a conserved modality in biofilm regulation, with distinct outputs in different organisms, and provides a paradigm for conditional, transcriptional control of c-di-GMP signaling pathways. The cellular c-di-GMP levels in wild-type (WT) and the rapA mutant were compared under P starvation conditions. While LapA was secreted by lapD mutants, it was not retained in the cell-associated protein fraction and was lost to the culture supernatant. This phenomenon is notably similar to what happens to LapA in these fractions when the WT is grown in low P, prompting investigation of LapD’s role in Pho regulon control of LapA localization, discussed. LapD and RapA both affect LapA localization to the cell surface, and was required for biofilm formation by the mutant. The description above represents the current extent of our knowledge about c-di-GMP signaling in strain Pf0-1. The Wsp chemosensory pathway regulates adherence and EPS production by strain SBW25 and PA01. Transcriptional regulation of RapA in Pf0-1 seems a relatively straightforward strategy for modulating c-di-GMP levels when compared to other mechanisms shown to regulate DGC and PDE activities, including allosteric activation, subcellular localization, and mRNA stability.

Citation: Newell P, O’Toole G. 2010. Environmental Control of Cyclic Di-GMP Signaling in : from Signal to Output, p 282-290. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch19
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Figure 1.

A schematic summarizing the current model for how phosphate concentration controls biofilm formation by is shown at the molecular (top) and microscopic (bottom) levels. Left: Low extracellar P is sensed by the PhoR/Pst system complex, and this leads to activation of the PhoR kinase and phosphorylation of PhoB. PhoB∼P forms a dimer and binds to the Pho Box sequence upstream of activating its transcription. The RapA protein cleaves c-di-GMP to form pGpG through its PDE activity, depleting cellular c-di-GMP pools. Decreased cellular c-di-GMP leads to dissociation of the nucleotide from the c-di-GMP effector LapD, and this signal promotes the egress of LapA to the culture supernatant. Cells cannot maintain stable surface attachments in low P. Right: Under high-P conditions RapA is not expressed, and c-di-GMP accumulates in the cell. LapD binds c-di-GMP and sends a signal promoting the maintenance of LapA on the cell surface. Cells can form irreversible attachments to the substratum and can go on to form a biofilm. IM, inner membrane; OM, outer membrane.

Citation: Newell P, O’Toole G. 2010. Environmental Control of Cyclic Di-GMP Signaling in : from Signal to Output, p 282-290. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch19
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1. Anderson, G. G., and, G. A. O’Toole. 2008. Innate and induced resistance mechanisms of bacterial biofilms. Curr. Top. Microbiol. Immunol. 322: 85105.
2. Arora, S. K.,, B. W. Ritchings,, E. C. Almira,, S. Lory, and, R. Ramphal. 1997. A transcriptional activator, FleQ, regulates mucin adhesion and flagellar gene expression in Pseudomonas aeruginosa in a cascade manner. J. Bacteriol. 179: 55745581.
3. Banin, E.,, M. L. Vasil, and, E. P. Greenberg. 2005. Iron and Pseudomonas aeruginosa biofilm formation. Proc. Natl. Acad. Sci. USA 102: 1107611081.
4. Bantinaki, E.,, R. Kassen,, C. G. Knight,, Z. Robinson,, A. J. Spiers, and, P. B. Rainey. 2007. Adaptive divergence in experimental populations of Pseudomonas fluorescens. III. Mutational origins of wrinkly spreader diversity. Genetics 176: 441453.
5. Capdevila, S.,, F. M. Martinez-Granero,, M. Sanchez-Contreras,, R. Rivilla, and, M. Martin. 2004. Analysis of Pseudomonas fluorescens F113 genes implicated in flagellar filament synthesis and their role in competitive root colonization. Microbiology 150: 38893897.
6. Casaz, P.,, A. Happel,, J. Keithan,, D. L. Read,, S. R. Strain, and, S. B. Levy. 2001. The Pseudomonas fluorescens transcription activator AdnA is required for adhesion and motility. Microbiology 147: 355361.
7. Compant, S.,, B. Duffy,, J. Nowak,, C. Clement, and, E. A. Barka. 2005. Use of plant growth-promoting bacteria for bio-control of plant diseases: principles, mechanisms of action, and future prospects. Appl. Environ. Microbiol. 71: 49514959.
8. Davey, M. E., and, G. A. O’Toole. 2000. Microbial biofilms: from ecology to molecular genetics. Microbiol. Mol. Biol. Rev. 64: 847867.
9. Espinosa-Urgel,, M.,, A. Salido, and, J. L. Ramos. 2000. Genetic analysis of functions involved in adhesion of Pseudomonas putida to seeds. J. Bacteriol. 182: 23632369.
10. Giddens, S. R.,, R. W. Jackson,, C. D. Moon,, M. A. Jacobs,, X. X. Zhang,, S. M. Gehrig, and, P. B. Rainey. 2007. Mutational activation of niche-specific genes provides insight into regulatory networks and bacterial function in a complex environment. Proc. Natl. Acad. Sci. USA 104: 1824718252.
11. Gjermansen, M.,, P. Ragas,, C. Sternberg,, S. Molin, and, T. Tolker-Nielsen. 2005. Characterization of starvation-induced dispersion in Pseudomonas putida biofilms. Environ. Microbiol. 7: 894906.
12. Gonin, M.,, E. M. Quardokus,, D. O’Donnol,, J. Maddock, and, Y. V. Brun. 2000. Regulation of stalk elongation by phosphate in Caulobacter crescentus. J. Bacteriol. 182: 337347.
13. Goymer, P.,, S. G. Kahn,, J. G. Malone,, S. M. Gehrig,, A., J. Spiers, and, P. B. Rainey. 2006. Adaptive divergence in experimental populations of Pseudomonas fluorescens. II. Role of the GGDEF regulator WspR in evolution and development of the wrinkly spreader phenotype. Genetics 173: 515526.
14. Haas, D., and, G. Defago. 2005. Biological control of soil-borne pathogens by fluorescent pseudomonads. Nat. Rev. Microbiol. 3: 307319.
15. Hickman, J. W., and, C. S. Harwood. 2008. Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor. Mol. Microbiol. 69: 376389.
16. Hickman, J. W.,, D. F. Tifrea, and, C. S. Harwood. 2005. A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. Proc. Natl. Acad. Sci. USA 102: 1442214427.
17. Hinsa, S. M.,, M. Espinosa-Urgel,, J. L. Ramos, and, G. A. O’Toole. 2003. Transition from reversible to irreversible attachment during biofilm formation by Pseudomonas fluorescens WCS365 requires an ABC transporter and a large secreted protein. Mol. Microbiol. 49: 905918.
18. Hinsa, S. M., and, G. A. O’Toole. 2006. Biofilm formation by Pseudomonas fluorescens WCS365: a role for LapD. Microbiology 152: 13751383.
19. Jackson, D. W.,, J. W. Simecka, and, T. Romeo. 2002. Catabolite repression of Escherichia coli biofilm formation. J. Bacteriol. 184: 34063410.
20. Jonas, K.,, A. N. Edwards,, R. Simm,, T. Romeo,, U. Römling, and, O. Melefors. 2008. The RNA binding protein CsrA controls cyclic di-GMP metabolism by directly regulating the expression of GGDEF proteins. Mol. Microbiol. 70: 236257.
21. Lamarche, M. G.,, B. L. Wanner,, S. Crepin, and, J. Harel. 2008. The phosphate regulon and bacterial virulence: a regulatory network connecting phosphate homeostasis and path-ogenesis. FEMS Microbiol. Rev. 32: 461473.
22. Lee, V. T.,, J. M. Matewish,, J. L. Kessler,, M. Hyodo,, Y. Hayakawa, and, S. Lory. 2007. A cyclic-di-GMP receptor required for bacterial exopolysaccharide production. Mol. Microbiol. 65: 14741488.
23. Malone, J. G.,, R. Williams,, M. Christen,, U. Jenal,, A. J. Spiers, and, P. B. Rainey. 2007. The structure-function relationship of WspR, a Pseudomonas fluorescens response regulator with a GGDEF output domain. Microbiology 153: 980994.
24. Martin, J. F. 2004. Phosphate control of the biosynthesis of antibiotics and other secondary metabolites is mediated by the PhoR-PhoP system: an unfinished story. J. Bacteriol. 186: 51975201.
25. Monds, R. D.,, P. D. Newell,, R. H. Gross, and, G. A. O’Toole. 2007. Phosphate-dependent modulation of c-di-GMP levels regulates Pseudomonas fluorescens Pf0-1 biofilm formation by controlling secretion of the adhesin LapA. Mol. Microbiol. 63: 659679.
26. Monds, R. D.,, P. D. Newell,, J. A. Schwartzman, and G. A. O’Toole. 2006. Conservation of the Pho regulon in Pseudomonas fluorescens Pf0-1. Appl. Environ. Microbiol. 72: 19101924.
27. Nelson, K. E.,, C. Weinel,, I. T. Paulsen,, R. J. Dodson,, H. Hilbert,, V. A. Martins dos Santos,, D. E. Fouts,, S. R. Gill,, M. Pop,, M. Holmes,, L. Brinkac,, M. Beanan,, R. T. DeBoy,, S. Daugherty,, J. Kolonay,, R. Madupu,, W. Nelson,, O. White,, J. Peterson,, H. Khouri,, I. Hance,, P. C. Lee,, E. Holtzapple,, D. Scanlan,, K. Tran,, A. Moazzez,, T. Utterback,, M. Rizzo,, K. Lee,, D. Kosack,, D. Moestl,, H. Wedler,, J. Lauber,, D. Stjepandic,, J. Hoheisel,, M. Straetz,, S. Heim,, C. Kiewitz,, J. A. Eisen,, K. N. Timmis,, A. Duosterhooft,, B. Tuommler, and, C. M. Fraser. 2002. Complete genome sequence and comparative analysis of the metabolically versatile Pseudomonas putida KT2440. Environ. Microbiol. 4: 799808.
28. Newell, P. D.,, R. D. Monds, and, G. A. O’Toole. 2009. LapD is a bis-(3′,5′)-cyclic dimeric GMP binding protein that regulates surface attachment by Pseudomonas fluorescens Pf0-1. Proc. Natl. Acad. Sci. USA 106: 34613466.
29. O’Toole,, G. A.,, K. A. Gibbs,, P. W. Hager,, P. V. Phibbs, Jr., and, R. Kolter. 2000. The global carbon metabolism regulator Crc is a component of a signal transduction pathway required for biofilm development by Pseudomonas aeruginosa. J. Bacteriol. 182: 425431.
30. O’Toole,, G. A., and, R. Kolter. 1998. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signalling pathways: a genetic analysis. Mol. Microbiol. 28: 449461.
31. Patriquin, G. M.,, E. Banin,, C. Gilmour,, R. Tuchman,, E. P. Greenberg, and, K. Poole. 2008. Influence of quorum sensing and iron on twitching motility and biofilm formation in Pseudomonas aeruginosa. J. Bacteriol. 190: 662671.
32. Paul, E. A., and, F. E. Clark. 1989. Soil as a habitat for organisms and their reactions, p. 13-30. In E. A. Paul and, F. E. Clark (ed.), Soil Microbiology and Biochemistry, vol. 2. Academic Press, San Diego, CA.
33. Paul, R.,, S. Abel,, P. Wassmann,, A. Beck,, H. Heerklotz, and, U. Jenal. 2007. Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization. J. Biol. Chem. 282: 2917029177.
34. Paul, R.,, S. Weiser,, N. C. Amiot,, C. Chan,, T. Schirmer,, B. Giese, and, U. Jenal. 2004. Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel diguanylate cyclase output domain. Genes Dev. 18: 715727.
35. Reva, O., and, B. Tummler. 2008. Think big—giant genes in bacteria. Environ. Microbiol. 10: 768777.
36. Robleto, E. A.,, I. Lopez-Hernandez,, M. W. Silby, and, S. B. Levy. 2003. Genetic analysis of the AdnA regulon in Pseudomonas fluorescens: nonessential role of flagella in adhesion to sand and biofilm formation. J. Bacteriol. 185: 453460.
37. Ryder, C.,, M. Byrd, and, D. J. Wozniak. 2007. Role of polysaccharides in Pseudomonas aeruginosa biofilm development. Curr. Opin. Microbiol. 10: 644648.
38. Shrout, J.,, D. Chopp,, C. Just,, M. Hentzer,, M. Givskov, and, M. Parsek. 2006. The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional. Mol. Microbiol. 62: 12641277.
39. Spiers, A. J.,, J. Bohannon,, S. M. Gehrig, and, P. B. Rainey. 2003. Biofilm formation at the air-liquid interface by the Pseudomonas fluorescens SBW25 wrinkly spreader requires an acetylated form of cellulose. Mol. Microbiol. 50: 1527.
40. Spiers, A. J.,, S. G. Kahn,, J. Bohannon,, M. Travisano, and, P. B. Rainey. 2002. Adaptive divergence in experimental populations of Pseudomonas fluorescens. I. Genetic and phenotypic bases of wrinkly spreader fitness. Genetics 161: 3346.
41. Taylor, B. L. 2007. Aer on the inside looking out: paradigm for a PAS-HAMP role in sensing oxygen, redox and energy. Mol. Microbiol. 65: 14151424.
42. Wang, X.,, A. K. Dubey,, K. Suzuki,, C. S. Baker,, P. Babitzke, and, T. Romeo. 2005. CsrA post-transcriptionally represses pgaABCD, responsible for synthesis of a biofilm polysaccharide adhesin of Escherichia coli. Mol. Microbiol. 56: 16481663.
43. Wanner, B. L. 1996. Phosphorus assimilation and control of the phosphate regulon, p. 1371. In F. C. Neidhart,, R. Curtiss III,, J. L. Ingraham,, E. C. C. Lin,, K. B. Low,, B. Magasanik, et al. (ed.), Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology. ASM Press, Washington, DC.
44. Wanner, B. L. 1996. Signal transduction in the control of phosphate-regulated genes of Escherichia coli. Kidney Int. 49: 964967.
45. Yousef-Coronado,, F.,, M. L. Travieso, and, M. Espinosa-Urgel. 2008. Different, overlapping mechanisms for colonization of abiotic and plant surfaces by Pseudomonas putida. FEMS Microbiol. Lett. 288: 118124.


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Table 1

Conservation of c-di-GMP signaling components and attachment factors among

Citation: Newell P, O’Toole G. 2010. Environmental Control of Cyclic Di-GMP Signaling in : from Signal to Output, p 282-290. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch19

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