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Chapter 11 : Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development
Author:
Caroline S. Harwood1
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Affiliations:
1: Department of Microbiology, The University of Washington, Seattle, WA 98195
Content Type: Monograph
Publication Year:
2010
Category: Microbial Genetics and Molecular Biology
Book DOI:
10.1128/9781555816667
Chapter DOI:
10.1128/9781555816667.ch11
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Abstract:
This chapter reviews cyclic di-GMP (c-di-GMP) metabolism and activity in Pseudomonas aeruginosa with a focus on how c-di-GMP modulates the expression and activities of genes and proteins required for biofilm formation. P. aeruginosa is an opportunistic human pathogen that persistently colonizes the lungs of people with cystic fibrosis (CF) and eventually kills them. The domain architectures of many of the proteins are discussed in the chapter. In P. aeruginosa, as in other bacteria, a high percentage of GGDEF and EAL domains are present as modules in proteins that have N-terminal domains implicated in ligand binding. The chapter describes three different assays used to visualize different but overlapping aspects of biofilms and then how they have been used to assess the effects of high and low intracellular c-di-GMP. The first and most commonly used assay is often referred to as the microtiter dish attachment assay. A second assay, often referred to as a continuous flow assay, involves growing biofilms on a surface of a small chamber through which growth medium is continuously flowed. A third measure of biofilm formation is colony morphology and dye binding. A systematic analysis of a P. aeruginosa transposon mutant library by the Lory laboratory and other more directed studies carried out by other investigators have identified just 8 of the 40 diguanylate cyclase (DGC) and phosphodiesterase (PDE) genes present in strain PAO1 as influencing biofilm formation. The chapter describes each of these genes and studies that have addressed their functions.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
Figures
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development
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Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig01
Figure 1.
Domain architectures of selected DGC and PDE proteins from P. aeruginosa.
10.1128/9781555816667/f0158-01_thmb.gif
10.1128/9781555816667/f0158-01.gif
Figure 1.
Domain architectures of selected DGC and PDE proteins from P. aeruginosa.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig02
Figure 2.
Loss of EPS production reverses the colony and attachment phenotypes of a wspF mutant. EPS is encoded by psl and pel genes in P. aeruginosa. (Top) Colony morphologies. (Bottom) Attachment assays were carried out in microtiter dish wells (J. W. Hickman and C. S. Harwood, unpublished data). OD, optical density.
10.1128/9781555816667/f0159-01_thmb.gif
10.1128/9781555816667/f0159-01.gif
Figure 2.
Loss of EPS production reverses the colony and attachment phenotypes of a wspF mutant. EPS is encoded by psl and pel genes in P. aeruginosa. (Top) Colony morphologies. (Bottom) Attachment assays were carried out in microtiter dish wells (J. W. Hickman and C. S. Harwood, unpublished data). OD, optical density.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig03
Figure 3.
Characteristics of the Wsp signal transduction system. (A) Organization of the genes encoding the Wsp system. (B) The Wsp proteins are predicted to be a membrane-bound methyl-accepting chemotaxis protein (WspA), a CheR-like methyltransferase (WspC), a CheB-like methylesterase (WspF), and two CheW homologues (WspB and WspD) that are predicted to serve as adapters between WspA and a hybrid histidine kinase response regulator (WspE). The response regulator protein, WspR, has a GGDEF domain and catalyzes the synthesis of c-di-GMP when phosphorylated. As described in the text, a wspF mutation is predicted to lock the Wsp system into a configuration where WspR is constantly phosphorylated and thus constantly producing c-di-GMP. (C) Physical organization of homologous Che proteins. (D) Colony morphologies of P. aeruginosa PAO1 wild-type and wsp deletion strains. wspF mutants have high levels of intracellular c-di-GMP relative to wild-type cells. Reprinted from Güvener and Harwood (
23
) with permission.
10.1128/9781555816667/f0162-01_thmb.gif
10.1128/9781555816667/f0162-01.gif
Figure 3.
Characteristics of the Wsp signal transduction system. (A) Organization of the genes encoding the Wsp system. (B) The Wsp proteins are predicted to be a membrane-bound methyl-accepting chemotaxis protein (WspA), a CheR-like methyltransferase (WspC), a CheB-like methylesterase (WspF), and two CheW homologues (WspB and WspD) that are predicted to serve as adapters between WspA and a hybrid histidine kinase response regulator (WspE). The response regulator protein, WspR, has a GGDEF domain and catalyzes the synthesis of c-di-GMP when phosphorylated. As described in the text, a wspF mutation is predicted to lock the Wsp system into a configuration where WspR is constantly phosphorylated and thus constantly producing c-di-GMP. (C) Physical organization of homologous Che proteins. (D) Colony morphologies of P. aeruginosa PAO1 wild-type and wsp deletion strains. wspF mutants have high levels of intracellular c-di-GMP relative to wild-type cells. Reprinted from Güvener and Harwood ( 23 ) with permission.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig04
Figure 4.
Phosphorylation is required for WspR cluster formation. The localization of WspR-YFP in ΔwspF wspR-yfp or ΔwspF ΔwspA wspR-yfp mutant cells are shown in the top panels, and the localization of two WspR-YFP mutant proteins in ΔwspF cells are shown in the bottom panels. Phase-contrast images of cells are shown on the left. Bar, 1 μm. Reprinted from Güvener and Harwood (
23
) with permission.
10.1128/9781555816667/f0163-01_thmb.gif
10.1128/9781555816667/f0163-01.gif
Figure 4.
Phosphorylation is required for WspR cluster formation. The localization of WspR-YFP in ΔwspF wspR-yfp or ΔwspF ΔwspA wspR-yfp mutant cells are shown in the top panels, and the localization of two WspR-YFP mutant proteins in ΔwspF cells are shown in the bottom panels. Phase-contrast images of cells are shown on the left. Bar, 1 μm. Reprinted from Güvener and Harwood ( 23 ) with permission.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig05
Figure 5.
Surface growth stimulates Wsp signal transduction as assayed by cluster formation of WspR-YFP. WspR-YFP localization in wild-type cells grown in liquid or on agar is shown. The phase-contrast (left) and fluorescence (right) images of cells expressing wspR-yfp are shown. Bar, 1 µm. Reprinted from Güvener and Harwood (
23
) with permission.
10.1128/9781555816667/f0163-02_thmb.gif
10.1128/9781555816667/f0163-02.gif
Figure 5.
Surface growth stimulates Wsp signal transduction as assayed by cluster formation of WspR-YFP. WspR-YFP localization in wild-type cells grown in liquid or on agar is shown. The phase-contrast (left) and fluorescence (right) images of cells expressing wspR-yfp are shown. Bar, 1 µm. Reprinted from Güvener and Harwood ( 23 ) with permission.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig06
Figure 6.
Structure of WspR in its active conformation. The site of c-di-GMP binding that leads to an inhibited conformation is also shown. From De et al. (
14
).
10.1128/9781555816667/f0164-01_thmb.gif
10.1128/9781555816667/f0164-01.gif
Figure 6.
Structure of WspR in its active conformation. The site of c-di-GMP binding that leads to an inhibited conformation is also shown. From De et al. ( 14 ).
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig07
Figure 7.
Predicted organization of the alginate biosynthesis complex. OM, outer membrane; PG, peptidoglycan; CM, cell membrane. Adapted from Ramsey and Wozniak (
63
) by J. Weadge, J. Whitney, C.-K. Keiski, A. N. Neculai, and P. L. Howell.
10.1128/9781555816667/f0164-02_thmb.gif
10.1128/9781555816667/f0164-02.gif
Figure 7.
Predicted organization of the alginate biosynthesis complex. OM, outer membrane; PG, peptidoglycan; CM, cell membrane. Adapted from Ramsey and Wozniak ( 63 ) by J. Weadge, J. Whitney, C.-K. Keiski, A. N. Neculai, and P. L. Howell.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig08
Figure 8.
Predicted organization of the Pel biosynthesis complex. OM, outer membrane; PG, peptidoglycan; CM, cell membrane. Courtesy of J. Weadge, J. Whitney, C.-K. Keiski, A. N. Neculai, and P. L. Howell.
10.1128/9781555816667/f0166-01_thmb.gif
10.1128/9781555816667/f0166-01.gif
Figure 8.
Predicted organization of the Pel biosynthesis complex. OM, outer membrane; PG, peptidoglycan; CM, cell membrane. Courtesy of J. Weadge, J. Whitney, C.-K. Keiski, A. N. Neculai, and P. L. Howell.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
/content/10.1128/9781555816667.ch11.ch11fig09
Figure 9.
Model for the regulation of gene expression by FleQ, FleN, and c-di-GMP. (A) FleQ in the absence of FleN or c-di-GMP maximally represses pel transcription. (B) Situation in wild-type cells. FleQ binding at the pelA promoter is reduced by FleN and ATP/ADP, resulting in less pel repression than the situation in panel A. (C) c-di-GMP binds to FleQ to cause it to dissociate from DNA, thereby causing derepression of transcription from the pel promoter. Reprinted from Hickman and Harwood (
29
) with permission.
10.1128/9781555816667/f0167-01_thmb.gif
10.1128/9781555816667/f0167-01.gif
Figure 9.
Model for the regulation of gene expression by FleQ, FleN, and c-di-GMP. (A) FleQ in the absence of FleN or c-di-GMP maximally represses pel transcription. (B) Situation in wild-type cells. FleQ binding at the pelA promoter is reduced by FleN and ATP/ADP, resulting in less pel repression than the situation in panel A. (C) c-di-GMP binds to FleQ to cause it to dissociate from DNA, thereby causing derepression of transcription from the pel promoter. Reprinted from Hickman and Harwood ( 29 ) with permission.
Citation:
Harwood C.
2010.
Role of Cyclic Di-GMP in Pseudomonas aeruginosa Biofilm Development,
p 156-172.
In
Wolfe A, Visick K (ed),
The Second Messenger Cyclic Di-GMP.
ASM Press, Washington, DC.
doi: 10.1128/9781555816667.ch11
References
/content/book/10.1128/9781555816667.ch11
1.
Alm, R. A.,, A. J. Bodero,, P. D. Free, and, J. S. Mattick. 1996. Identification of a novel gene, pilZ, essential for type 4 fimbrial biogenesis in Pseudomonas aeruginosa. J. Bacteriol. 178: 46– 53.
2.
Alvarez-Ortega,, C., and, C. S. Harwood. 2007. Identification of a malate chemoreceptor in Pseudomonas aeruginosa by screening for chemotaxis defects in an energy taxis-deficient mutant. Appl. Environ. Microbiol. 73: 7793– 7795.
3.
Amikam, D., and, M. Y. Galperin. 2006. PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22: 3– 6.
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: 441– 453.
5.
Baty, A. M.,, Z. Diwu,, G. Dunham,, C. C. Eastburn,, G. G. Geesey,, A. E. Goodman,, P. A. Suci, and, S. Techkarnjanaruk. 2001. Characterization of extracellular chitinolytic activity in biofilms. Methods Enzymol. 336: 279– 301.
6.
Boucher, J. C.,, H. Yu,, M. H. Mudd, and, V. Deretic. 1997. Mucoid Pseudomonas aeruginosa in cystic fibrosis: characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection. Infect. Immun. 65: 3838– 3846.
7.
Brencic, A., and, S. Lory. 2009. Determination of the regulon and identification of novel mRNA targets of Pseudomonas aeruginosa RsmA. Mol. Microbiol. 72: 612– 632.
8.
Christen, M.,, B. Christen,, M. Folcher,, A. Schauerte, and, U. Jenal. 2005. Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP. J. Biol. Chem. 280: 30829– 30837.
9.
Chung, I. Y.,, K. B. Choi,, Y. J. Heo, and, Y. H. Cho. 2008. Effect of PEL exopolysaccharide on the wspF mutant phenotypes in Pseudomonas aeruginosa PA14. J. Microbiol. Biotechnol. 18: 1227– 1234.
10.
D’Argenio,, D. A.,, M. W. Calfee,, P. B. Rainey, and, E. C. Pesci. 2002. Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants. J. Bacteriol. 184: 6481– 6489.
11.
Dasgupta, N.,, S. K. Arora, and, R. Ramphal. 2000. fleN, a gene that regulates flagellar number in Pseudomonas aeruginosa. J. Bacteriol. 182: 357– 364.
12.
Dasgupta, N.,, E. P. Ferrell,, K. J. Kanack,, S. E. West, and, R. Ramphal. 2002. fleQ, the gene encoding the major flagellar regulator of Pseudomonas aeruginosa, is sigma70 dependent and is downregulated by Vfr, a homolog of Escherichia coli cyclic AMP receptor protein. J. Bacteriol. 184: 5240– 5250.
13.
Dasgupta, N.,, M. C. Wolfgang,, A. L. Goodman,, S. K. Arora,, J. Jyot,, S. Lory, and, R. Ramphal. 2003. A four-tiered transcriptional regulatory circuit controls flagellar biogenesis in Pseudomonas aeruginosa. Mol. Microbiol. 50: 809– 824.
14.
De, N.,, M. V. A. S. Navarro,, R. V. Raghavan, and H. Son-dermann. 2009. Determinants for the activation and autoinhibition of the diguanylate cyclase response regulator WspR. J. Mol. Biol. doi:10.1016/j.jmb.2009.08.030.
15.
De, N.,, M. Pirruccello,, P. V. Krasteva,, N. Bae,, R. V. Raghavan, and, H. Sondermann. 2008. Phosphorylation-independent regulation of the diguanylate cyclase WspR. PLoS Biol. 6: e67.
16.
Drenkard, E., and, F. M. Ausubel. 2002. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416: 740– 743.
17.
Friedman, L., and, R. Kolter. 2004. Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms. Mol. Microbiol. 51: 675– 690.
18.
Friedman, L., and, R. Kolter. 2004. Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aeruginosa biofilm matrix. J. Bacteriol. 186: 4457– 4465.
19.
Galperin, M. Y.,, T. A. Gaidenko,, A. Y. Mulkidjanian,, M. Nakano, and, C. W. Price. 2001. MHYT, a new integral membrane sensor domain. FEMS Microbiol. Lett. 205: 17– 23.
20.
Galperin, M. Y.,, A. N. Nikolskaya, and, E. V. Koonin. 2001. Novel domains of the prokaryotic two-component signal transduction systems. FEMS Microbiol. Lett. 203: 11– 21.
21.
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: 18247– 18252.
22.
Gomez, M. I., and, A. Prince. 2007. Opportunistic infections in lung disease: Pseudomonas infections in cystic fibrosis. Curr. Opin. Pharmacol. 7: 244– 251.
23.
Govan, J. R., and, V. Deretic. 1996. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Rev. 60: 539– 574.
24.
Güvener, Z. T., and, C. S. Harwood. 2007. Subcellular location characteristics of the Pseudomonas aeruginosa GGDEF protein, WspR, indicate that it produces cyclic-di-GMP in response to growth on surfaces. Mol. Microbiol. 66: 1459– 1473.
25.
Güvener, Z. T.,, D. F. Tifrea, and, C. S. Harwood. 2006. Two different Pseudomonas aeruginosa chemosensory signal transduction complexes localize to cell poles and form and remould in stationary phase. Mol. Microbiol. 61: 106– 118.
26.
Haussler, S.,, B. Tummler,, H. Weissbrodt,, M. Rohde, and, I. Steinmetz. 1999. Small-colony variants of Pseudomonas aeruginosa in cystic fibrosis. Clin. Infect. Dis. 29: 621– 625.
27.
Hay, I. D.,, U. Remminghorst, and, B. H. Rehm. 2009. MucR, a novel membrane-associated regulator of alginate biosynthesis in Pseudomonas aeruginosa. Appl. Envrion. Microbiol. 75: 1110– 1120.
28.
Hengge, R. 2009. Principles of c-di-GMP signaling in bacteria. Nat. Rev. Microbiol. 7: 263– 273.
29.
Heydorn, A.,, B. K. Ersboll,, M. Hentzer,, M. R. Parsek,, M. Givskov, and, S. Molin. 2000. Experimental reproducibility in flow-chamber biofilms. Microbiology 146: 2409– 2415.
30.
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: 376– 389.
31.
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: 14422– 14427.
32.
Hoffman, L. R.,, D. A. D’Argenio,, M. J. MacCoss,, Z. Zhang,, R. A. Jones, and, S. I. Miller. 2005. Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436: 1171– 1175.
33.
Hoiby, N. 2002. New antimicrobials in the management of cystic fibrosis. J. Antimicrob. Chemother. 49: 235– 238.
34.
Hoiby, N. 2002. Understanding bacterial biofilms in patients with cystic fibrosis: current and innovative approaches to potential therapies. J. Cyst. Fibros. 1: 249– 254.
35.
Jackson, K. D.,, M. Starkey,, S. Kremer,, M. R. Parsek, and, D. J. Wozniak. 2004. Identification of psl, a locus encoding a potential exopolysaccharide that is essential for Pseudomonas aeruginosa PAO1 biofilm formation. J. Bacteriol. 186: 4466– 4475.
36.
Jenal, U., and, J. Malone. 2006. Mechanisms of cyclic-di-GMP signaling in bacteria. Annu. Rev. Genet. 40: 385– 407.
37.
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: 236– 257.
38.
Kazmierczak, B. I.,, M. B. Lebron, and, T. S. Murray. 2006. Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa. Mol. Microbiol. 60: 1026– 1043.
39.
Kirisits, M. J.,, L. Prost,, M. Starkey, and, M. R. Parsek. 2005. Characterization of colony morphology variants isolated from Pseudomonas aeruginosa biofilms. Appl. Environ. Microbiol. 71: 4809– 4821.
40.
Kohler, T.,, L. K. Curty,, F. Barja,, C. van Delden, and, J. C. Pechere. 2000. Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J. Bacteriol. 182: 5990– 5996.
41.
Kuchma, S. L.,, K. M. Brothers,, J. H. Merritt,, N. T. Liberati,, F. M. Ausubel, and G. A. O’Toole. 2007. BifA, a cyclic-di-GMP phosphodiesterase, inversely regulates biofilm formation and swarming motility by Pseudomonas aeruginosa PA14. J. Bacteriol. 189: 8165– 8178.
42.
Kuchma, S. L.,, J. P. Connolly, and, G. A. O’Toole. 2005. A three-component regulatory system regulates biofilm maturation and type III secretion in Pseudomonas aeruginosa. J. Bacteriol. 187: 1441– 1454.
43.
Kulasekara, H.,, V. Lee,, A. Brencic,, N. Liberati,, J. Urbach,, S. Miyata,, D. G. Lee,, A. N. Neely,, M. Hyodo,, Y. Hayakawa,, F. M. Ausubel, and, S. Lory. 2006. Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3′-5′)-cyclic-GMP in virulence. Proc. Natl. Acad. Sci. USA 103: 2839– 2844.
44.
Kulasekara, H. D.,, I. Ventre,, B. R. Kulasekara,, A. Lazdunski,, A. Filloux, and, S. Lory. 2005. A novel two-component system controls the expression of Pseudomonas aeruginosa fimbrial cup genes. Mol. Microbiol. 55: 368– 380.
45.
Lapouge, K.,, M. Schubert,, F. H. Allain, and, D. Haas. 2008. Gac/Rsm signal transduction pathway of gammaproteobacteria: from RNA recognition to regulation of social behaviour. Mol. Microbiol. 67: 241– 253.
46.
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: 1474– 1484.
47.
Lyczak, J. B.,, C. L. Cannon, and, G. B. Pier. 2000. Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect. 2: 1051– 1060.
48.
Maddock, J. R., and, L. Shapiro. 1993. Polar location of the chemoreceptor complex in the Escherichia coli cell. Science 259: 1717– 1723.
49.
Mah, T. F., and, G. A. O’Toole. 2001. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 9: 34– 39.
50.
Martin, D. W.,, M. J. Schurr,, M. H. Mudd,, J. R. Govan,, B. W. Holloway, and, V. Deretic. 1993. Mechanism of conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 90: 8377– 8381.
51.
Matsukawa, M., and, E. P. Greenberg. 2004. Putative exopolysaccharide synthesis genes influence Pseudomonas aeruginosa biofilm development. J. Bacteriol. 186: 4449– 4456.
52.
McCarter, L. L. 2006. Regulation of flagella. Curr. Opin. Microbiol. 9: 180– 186.
53.
Merighi, M.,, V. T. Lee,, M. Hyodo,, Y. Hayakawa, and, S. Lory. 2007. The second messenger bis-(3′-5′)-cyclic-GMP and its PilZ domain-containing receptor Alg44 are required for alginate biosynthesis in Pseudomonas aeruginosa. Mol. Microbiol. 65: 876– 895.
54.
Merritt, J.,, K. Brothers,, S. L. Kuchma, and, G. O’Toole. 2007. SadC reciprocally influences biofilm formation and swarming motility via modulation of exopolysaccharide production and flagellar function. J. Bacteriol. 189: 8154– 8164.
55.
Minasov, G.,, S. Padavattan,, L. Shuvalova,, J. S. Brunzelle,, D. J. Miller,, A. Basle,, C. Massa,, F. R. Collart,, T. Schirmer, and, W. F. Anderson. 2009. Crystal structures of YkuI and its complex with second messenger c-di-GMP suggests catalytic mechanism of phosphodiester bond cleavage by EAL domains. J. Biol. Chem. 284: 13174– 13184.
56.
Navarro,, M. V. A. S.,, N. De,, N. Bae,, Q. Wang, and, H. Sondermann. 2009. Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX. Structure 17: 1104– 1116.
57.
Oglesby, L. L.,, S. Jain, and, D. E. Ohman. 2008. Membrane topology and roles of Pseudomonas aeruginosa Alg8 and Alg44 in alginate polymerization. Microbiology 154: 1605– 1615.
58.
O’Toole,, G. A., and, R. Kolter. 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 30: 295– 304.
59.
Parales, R. E.,, A. Ferrandez, and, C. S. Harwood. 2004. Chemotaxis in pseudomonads, p. 793-815. In J.-L. Ramos (ed.), Pseudomonas, vol. 1. Genomics, Life Style and Molecular Architecture. Kluwer Academic/Plenum Publishers, New York, NY.
60.
Parsek, M. R., and, P. K. Singh. 2003. Bacterial biofilms: an emerging link to disease pathogenesis. Annu. Rev. Microbiol. 58: 677– 701.
61.
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: 29170– 219177.
62.
Rainey, P. B., and, M. Travisano. 1998. Adaptive radiation in a heterogeneous environment. Nature 394: 69– 72.
63.
Rajan, S., and, L. Saiman. 2002. Pulmonary infections in patients with cystic fibrosis. Semin. Respir. Infect. 17: 47– 56.
64.
Ramelot, T. A.,, A. Yee,, J. R. Cort,, A. Semesi,, C. H. Arrowsmith, and, M. A. Kennedy. 2007. NMR structure and binding studies confirm that PA4608 from Pseudomonas aeruginosa is a PilZ domain and a c-di-GMP binding protein. Proteins 66: 266– 271.
65.
Ramsey, D. M., and, D. J. Wozniak. 2005. Understanding the control of Pseudomonas aeruginosa alginate synthesis and the prospects for management of chronic infections in cystic fi-brosis. Mol. Microbiol. 56: 309– 322.
66.
Rao, F.,, Y. Yang,, Y. Qi, and, Z. X. Liang. 2008. Catalytic mechanism of cyclic di-GMP-specific phosphodiesterase: a study of the EAL domain-containing RocR from Pseudomonas aeruginosa. J. Bacteriol. 190: 3622– 3631.
67.
Rao, F.,, Y. Qi,, H. S. Chong,, M. Kotaka,, B. Li,, J. Li,, J. Lescar,, K. Tang, and, Z. X. Liang. 17 April 2009. The functional role of a conserved loop in EAL domain-based cyclic di-GMP-specific phosphodiesterase. J. Bacteriol. 191: 4722– 4731.
68.
Remminghorst, U., and, B. H. Rehm. 2006. Alg44, a unique protein required for alginate biosynthesis in Pseudomonas aeruginosa. FEBS Lett. 580: 3883– 3888.
69.
Remminghorst, U., and, B. H. Rhem. 2006. Bacterial alginates: from biosynthesis to applications. Biotechnol. Lett. 28: 1701– 1712.
70.
Romling, U.,, M. Gomelsky, and, M. Y. Galperin. 2005. C-di-GMP: the dawning of a novel bacterial signalling system. Mol. Microbiol. 57: 629– 639.
71.
Rowen, D. W., and, V. Deretic. 2000. Membrane-to-cytosol redistribution of ECF sigma factor AlgU and conversion to mucoidy in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Mol. Microbiol. 36: 314– 327.
72.
Ryan, R. P.,, J. Lucey,, K. O’Donovan,, Y. McCarthy,, L. Yang,, T. Tolker-Nielsen, and, J. M. Dow. 2009. HD-GYP domain proteins regulate biofilm formation and virulence in Pseudomonas aeruginosa. Environ. Microbiol. 11: 1126– 1136.
73.
Ryan, R. P.,, Y. Fouhy,, J. F. Lucey,, L. C. Crossman,, S. Spiro,, Y. W. He,, L. H. Zhang,, S. Heeb,, M. Camara,, P. Williams, and, J. M. Dow. 2006. Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein that functions in cyclic di-GMP turnover. Proc. Natl. Acad. Sci. USA 103: 6712– 6717.
74.
Ryder, C.,, M. Byrd, and, D. Wozniak. 2007. Role of polysaccharides in Pseudomonas aeruginosa biofilm development. Curr. Opin. Microbiol. 10: 664– 648.
75.
Schmidt, A. J.,, D. A. Ryjenkov, and, M. Gomelsky. 2005. The ubiquitous protein domain EAL is a cyclic diguanylate-specific phosphodiesterase: enzymatically active and inactive EAL domains. J. Bacteriol. 187: 4774– 4781.
76.
Singh, P. K.,, A. L. Schaefer,, M. R. Parsek,, T. O. Moninger,, M. J. Welsh, and, E. P. Greenberg. 2000. Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms. Nature 407: 762– 764.
77.
Smith, E. E.,, D. G. Buckley,, Z. Wu,, C. Saenphimmachak,, L. R. Hoffman,, D. A. D’Argenio,, S. I. Miller,, B. W. Ramsey,, D. P. Speert,, S. M. Moskowitz,, J. L. Burns,, R. Kaul, and, M. V. Olson. 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 103: 8487– 8492.
78.
Sourjik, V., and, H. C. Berg. 2000. Localization of components of the chemotaxis machinery of Escherichia coli using fluorescent protein fusions. Mol. Microbiol. 37: 740– 751.
79.
Starkey, M.,, J. H. Hickman,, L. Ma,, N. Zhang,, S. De Long,, A. Hinz,, S. Palacios,, C. Manoil,, M. J. Kirisits,, T. D. Starner,, D. J. Wozniak,, C. S. Harwood, and, M. R. Parsek. 27 March 2009. Pseudomonas aeruginosa rugose small-colony variants have adaptations that likely promote persistence in the cystic fibrosis lung. J. Bacteriol. 191: 3492– 3503.
80.
Taguchi, K.,, H. Fukutomi,, A. Kuroda,, J. Kato, and, H. Ohtake. 1997. Genetic identification of chemotactic transducers for amino acids in Pseudomonas aeruginosa. Microbiology 143: 3223– 3229.
81.
Tamayo, R.,, J. T. Pratt, and, A. Camilli. 2007. Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu. Rev. Microbiol. 61: 131– 148.
82.
Vallet, I.,, J. W. Olson,, S. Lory,, A. Lazdunski, and, A. Filloux. 2001. The chaperone/usher pathways of Pseudomonas aeruginosa: identification of fimbrial gene clusters ( cup) and their involvement in biofilm formation. Proc. Natl. Acad. Sci. USA 98: 6911– 6916.
83.
Vasseur, P.,, I. Vallet-Gely,, C. Soscia,, S. Genin, and, A. Filloux. 2005. The pel genes of the Pseudomonas aeruginosa PAK strains are involved in early and late stages of biofilm formation. Microbiology 151: 985– 997.
84.
Wagner, V. E., and, B. H. Iglewski. 2008. P. aeruginosa biofilms in CF infection. Clin. Rev. Allergy Immunol. 35: 124– 134.
85.
Wassmann, P.,, C. Chan,, R. Paul,, A. Beck,, H. Heerklotz,, U. Jenal, and, T. Schirmer. 2007. Structure of BeF3-modified response regulator PleD: implications for diguanylate cyclase activation, catalysis, and feedback inhibition. Structure 15: 915– 927.
86.
Weinhouse, H.,, S. Sapir,, D. Amikam,, Y. Shilo,, G. Volman,, P. Ohana, and, M. Benziman. 1997. C-di-GMP-binding protein, a new factor regulating cellulose synthesis in Acetobacter xylinum. FEBS Lett. 416: 207– 211.
87.
Whitchurch, C. B.,, A. J. Leech,, M. D. Young,, D. Kennedy,, J. L. Sargent,, J. J. Bertrand,, A. B. Semmler,, A. S. Mellick,, P. R. Martin,, R. A. Alm,, M. Hobbs,, S. A. Beatson,, B. Huang,, L. Nguyen,, J. C. Commolli,, J. N. Engel,, A. Darzins, and, J. S. Mattick. 2004. Characterization of a complex chemosensory signal transduction system which controls twitching motility in Pseudomonas aeruginosa. Mol. Microbiol. 52: 873– 893.
88.
Wolfe, A. J., and, K. L. Visick. 2008. Get the message out: cyclic-di-GMP regulates multiple levels of flagellum-based motility. J. Bacteriol. 190: 463– 475.
89.
Wozniak, D. J.,, T. J. Wyckoff,, M. Starkey,, R. Keyser,, P. Azadi,, G. A. O’Toole, and, M. R. Parsek. 2003. Alginate is not a significant component of the extracellular polysaccharide matrix of PA14 and PAO1 Pseudomonas aeruginosa biofilms. Proc. Natl. Acad. Sci. USA 100: 7907– 7912.
90.
Zhulin, I. B.,, A. N. Nikolskaya, and, M. Y. Galperin. 2003. Common extracellular sensory domains in transmembrane receptors for diverse signal transduction pathways in Bacteria and Archaea. J. Bacteriol. 185: 285– 294.