Chapter 14 : Csr (Rsm) System and Its Overlap and Interplay with Cyclic Di-GMP Regulatory Systems

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Free-living bacteria must respond rapidly to changing environmental and physiological conditions to survive stresses, maintain homeostasis and growth, and compete with other species. This chapter describes recent evidence of shared regulatory targets and interconnections between two global regulatory systems that antagonistically influence bacterial lifestyle choices by governing surface properties, biofilm development, motility, and in many species, virulence factors. The CsrD protein, which triggers the turnover of CsrB and CsrC RNAs by RNaseE, contains degenerate GGDEF and EAL domains but does not synthesize or degrade cyclic di-GMP (c-di-GMP). The chapter illustrates the interactions of Csr and its interplay with c-di-GMP global regulatory systems. Various features of the Csr (Rsm) system have been the subjects of previous reviews. BarA-UvrY homologs, which are present in many gram-negative bacteria, are variously known as Gac, Var, Exp, and Let two-component signal transduction system (TCS), and also work in conjunction with Csr systems. Importantly, the BarA-UvrY system also activates rpoS transcription in , possibly through DNA binding by the response regulator UvrY. Synthesis of c-di-GMP from two GTPs is catalyzed by diguanylate cyclases (DGC) that contain the GGDEF (DUF-1) domain. A recently discovered c-di-GMP binding element is not a protein but a riboswitch. This c-di-GMP binding RNA domain or aptamer was originally identified as a conserved GEMM sequence motif (genes for the environment, membranes, and motility) in the 5'-untranslated segment of numerous mRNAs involved in c-di-GMP metabolism, virulence, motility, and pilus formation.

Citation: Romeo T, Babitzke P. 2010. Csr (Rsm) System and Its Overlap and Interplay with Cyclic Di-GMP Regulatory Systems, p 201-214. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch14

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Two-Component Signal Transduction Systems
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Image of Figure 1.
Figure 1.

Csr components and circuitry based on the system. (A) Ribbon diagram of the CsrA dimer. The two poly-peptides are interdigitated within the dimer. The first and fifth beta strands of opposite polypeptides (β-1 and β-5′; β-1’ and β-5) are parallel in the dimer. These parallel strands form two surfaces for RNA binding (one of which is circled), located on opposite sides of the protein ( ). (B) Predicted secondary structure and CsrA binding sites of CsrB RNA. The boldface and numbered GGA-containing sequences (most frequent, CAGGAUG) in the predicted loops or unstructured RNA, respectively, may serve as binding sites for CsrA ( ). The terminal stem-loop is a putative factor-independent terminator (Ter). nt, nucleotides. (C) Domain predictions for CsrD protein. TM, transmembrane; CC, coiled coil; PL, periplasmic loop; HAMP, HAMP-like domain; aa, amino acids. GGDEF and EAL domains are shown along with the noncanonical sequences in CsrD. The sequence ENQL at residues 581 to 584 is 100% conserved in apparent CsrD orthologs but is not present in other EAL domain proteins and is important for CsrD function ( ). (D) Wire diagram of Csr circuitry. X is an unknown regulator of BarA activity, which is regulated by CsrA ( ). BarA and UvrY are the two component signal transduction sensor kinase and response regulator, respectively, which activate and transcription ( ). SdiA is the homolog of LuxR, which responds to HSL and activates transcription ( ). RNase E and polynucleotide phospho-rylase (PNPase), are ribonucleases involved in CsrD-dependent decay of CsrB and CsrC ( ). Activation and repression are depicted using arrowheads and perpendicular lines, respectively. Two apparent autoregulatory loops are shown for CsrA (via SdiA and BarA) and one for UvrY (via BarA). Such regulation is evidence of tight and finely tuned control of CsrA activity within this circuitry.

Citation: Romeo T, Babitzke P. 2010. Csr (Rsm) System and Its Overlap and Interplay with Cyclic Di-GMP Regulatory Systems, p 201-214. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch14
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Image of Figure 2.
Figure 2.

Multitier repression of biofilm formation by CsrA. The regulatory circuitry by which Csr regulates or is posited to regulate biofilm formation at several levels in is shown. The binding of CsrA to the transcript leader at six sites represses translation of and destabilizes this transcript. This operon is needed for production, covalent modification, and secretion of the adhesive polysaccharide PGA ( ). CsrA binds specifically to transcripts for GGDEF proteins, including YdeH and YcdT, which synthesize c-di-GMP. Thus, CsrA represses levels of c-di-GMP in ( ). c-di-GMP somehow activates PGA production ( ). CsrA represses glycogen synthesis and turnover ( ), which also affects biofilm formation ( ). A possible biochemical pathway for this effect is shown, in which carbon flow into the synthesis of UDP-acetylglucosamine, the precursor of the adhesin PGA, is limited by CsrA repression of genes, by ( ), and perhaps, by regulation of the and genes ( ). Transcription of mRNA requires the NhaR LysR family DNA binding protein, which may represent another point of Csr regulation, based on the observation that the transcript copurifies with CsrA ( ). Conversely, CsrA activates motility by stabilizing mRNA ( ). OM, outer membrane; CM, cytoplasmic membrane.

Citation: Romeo T, Babitzke P. 2010. Csr (Rsm) System and Its Overlap and Interplay with Cyclic Di-GMP Regulatory Systems, p 201-214. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch14
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Image of Figure 3.
Figure 3.

Convergence of Csr and c-di-GMP regulation in CsrA and c-di-GMP have inverse effects on motility versus sessility. CsrA activates motility and represses biofilm formation, while c-di-GMP represses motility and activates biofilm formation. CsrA posttranscriptionally activates the master operon of the motility cascade, and is required for flagellum biosynthesis ( ), while it represses the structural genes for production, covalent modification, and secretion of the biofilm adhesin PGA ( ). CsrA represses genes for c-di-GMP biosynthesis ( ), including which is important for biofilm formation and PGA synthesis ( ). Because CsrA activates it should indirectly activate σ, the motility sigma factor that is under FlhDC control, and in turn should activate ( ), although this indirect effect was not apparent in array studies ( ). The latter gene encodes a c-di-GMP-specific PDE, which represses biofilm formation ( ). Because CsrA represses c-di-GMP production ( ), it might activate motility indirectly through effects on the PilZ domain protein, YcgR, although this remains to be seen. c-di-GMP activates expression of curli fimbriae ( ) and PGA production ( ) by undetermined mechanisms. Several feedback loops are apparent in this system: CsrA-BarA-UvrY-CsrB/C ( ), BarA-UvrY ( ), CsrA-CsrD-CsrB/C ( ), and NhaR, which activates its own transcription ( ) and that between CsrA and . In principle, may be regulated by CsrA through its effects on BarA-UvrY signaling ( ), which affects transcription ( ), or its effect on translation ( ), as Hfq functions as an RNA chaperone that mediates the positive effects of two antisense RNA regulators on translation ( ). In turn, σ has multiple regulatory effects on c-di-GMP and expression of genes for curli fimbriae ( ). The asterisk between σ and CsrA indicates conditional modest effects of on transcripts ( ). Not shown are the inverse effects of CsrA and σ on glycogen biosynthesis ( ). The question mark indicates that CsrA is predicted to repress translation ( ).

Citation: Romeo T, Babitzke P. 2010. Csr (Rsm) System and Its Overlap and Interplay with Cyclic Di-GMP Regulatory Systems, p 201-214. In Wolfe A, Visick K (ed), The Second Messenger Cyclic Di-GMP. ASM Press, Washington, DC. doi: 10.1128/9781555816667.ch14
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1. Agladze, K.,, X. Wang, and, T. Romeo. 2005. Spatial periodicity of Escherichia coli K-12 biofilm microstructure initiates during a reversible, polar attachment phase of development and requires the polysaccharide adhesin PGA. J. Bacteriol. 187:82378246.
2. Ahmer, B. M. 2004. Cell-to-cell signalling in Escherichia coli and Salmonella enterica. Mol. Microbiol. 52:933945.
3. Amikam, D., and, M. Y. Galperin. 2006. PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22:36.
4. Babitzke, P., and, T. Romeo. 2007. CsrB sRNA family: sequestration of RNA-binding regulatory proteins. Curr. Opin. Microbiol. 10:156163.
5. Baker, C. S.,, L. A. Eory,, H. Yakhnin,, J. Mercante,, T. Romeo, and, P. Babitzke. 2007. CsrA inhibits translation initiation of Escherichia coli hfq by binding to a single site overlapping the Shine-Dalgarno sequence. J. Bacteriol. 189:54725481.
6. Baker, C. S.,, I. Morozov,, K. Suzuki,, T. Romeo, and, P. Babitzke. 2002. CsrA regulates glycogen biosynthesis by preventing translation of glgC in Escherichia coli. Mol. Microbiol. 44:15991610.
7. Barnard, F. M.,, M. F. Loughlin,, H. P. Fainberg,, M. P. Messenger,, D. W. Ussery,, P. Williams, and, P. J. Jenks. 2004. Global regulation of virulence and the stress response by CsrA in the highly adapted human gastric pathogen Helicobacter pylori. Mol. Microbiol. 51:1532.
8. Bejerano-Sagie,, M., and, K. B. Xavier. 2007. The role of small RNAs in quorum sensing. Curr. Opin. Microbiol. 10:189198.
9. Benach, J.,, S. S. Swaminatha,, R. Tamayo,, S. K. Handelman,, E. Folta-Stogniew,, J. E. Ramos,, F. Forouhar,, H. Neely,, J. Seetharaman,, A. Camilli, and, J. F. Hunt. 2007. The structural basis of cyclic diguanylate signal transduction by PilZ domains. EMBO J. 26:51535166.
10. Bobrov, A. G.,, O. Kirillina,, S. Forman,, D. Mack, and, R. D. Perry. 2008. Insights into Yersinia pestis biofilm development: topology and co-interaction of Hms inner membrane proteins involved in exopolysaccharide production. Environ. Microbiol. 10:14191432.
11. Bonafonte, M. A.,, C. Solano,, B. Sesma,, M. Alvarez,, L. Montuenga,, D. Garcla-Ros, and, C. Gamazo. 2000. The relationship between glycogen synthesis, biofilm formation and virulence in Salmonella enteritidis. Microbiol. Lett. 191:3136.
12. Christen, B.,, M. Christen,, R. Paul,, F. Schmid,, M. Folcher,, P. Jenoe,, M. Meuwly, and, U. Jenal. 2006. Allosteric control of cyclic di-GMP signaling. J. Biol. Chem. 281:3201532024.
13. Condon, C. 2007. Maturation and degradation of RNAin bacteria. Curr. Opin. Microbiol. 10:271278.
14. Corona-Izquierdo,, F. P., and, Membrillo-Hernandez J. 2002. A mutation in rpoS enhances biofilm formation in Escherichia coli during exponential phase of growth. FEMS Microbiol. Lett. 211:105110.
15. Cui, Y.,, A. Chatterjee, and, A. K. Chatterjee. 2001. Effects of the two-component system comprising GacA and GacS of Erwinia carotovora subsp. carotovora on the production of global regulatory rsmB RNA, extracellular enzymes, and harpinEcc. Mol. Plant-Microbe Interact. 14:516526.
16. Dong, T., and, H. E. Schellhorn. 2008. Control of RpoS in global gene expression of Escherichia coli in minimal media. Mol. Genet. Genomics 281:1933.
17. Dover, N., and, E. Padan. 2001. Transcription of nhaA, the main Na+/H+ antiporter of Escherichia coli, is regulated by Na+ and growth phase. J. Bacteriol. 183:644653.
18. Dow, J. M.,, Y. Fouhy,, J. F. Lucey, and, R. P. Ryan. 2006. The HD-GYP domain, cyclic di-GMP signaling, and bacterial virulence to plants. Mol. Plant-Microbe Interact. 19:13781384.
19. Dubey, A. K.,, C. S. Baker,, T. Romeo, and, P. Babitzke. 2005. RNA sequence and secondary structure participate in high-affinity CsrA-RNA interaction. RNA 11:15791587.
20. Dubey, A. K.,, C. S. Baker,, K. Suzuki,, A. D. Jones,, P. Pandit,, T. Romeo, and, P. Babitzke. 2003. CsrA regulates translation of the Escherichia coli carbon starvation gene, cstA, by blocking ribosome access to the cstA transcript. J. Bacteriol. 185:44504560.
21. Edwards, A. N.,, J. W. Mercante,, P. Babitzke, and, T. Romeo. 2008. Determination of the global regulatory role of CsrA in Escherichia coli, abstr. H-067, p. 295. Abstr. 108th Gen. Meet. Am. Soc. Microbiol., Boston, MA.
22. Evangelista, M.,, C. S. Baker,, T. Romeo, and, P. Babitzke. 2008. CsrA activates expression of sdiA, the gene encoding the Escherichia coli homoserine lactone receptor, abstr. H-141, p. 310. Abstr. 108th Gen. Meet. Am. Soc. Microbiol., Boston, MA.
23. Ferreira, R. B.,, L. C. Antunes,, E. P. Greenberg, and, L. L. McCarter. 2008. Vibrio parahaemolyticus ScrC modulates cyclic dimeric GMP regulation of gene expression relevant to growth on surfaces. J. Bacteriol. 190:851860.
24. Fields, J. A., and, S. A. Thompson. 2008. Campylobacter jejuni CsrA mediates oxidative stress responses, biofilm formation, and host cell invasion. J. Bacteriol. 190:34113416.
25. Furukawa, S.,, S. L. Kuchma, and, G.A. O’Toole. 2006. Keeping options open: acute versus persistent infections. J. Bacteriol. 188:12111217.
26. Galperin, M. Y.,, A. N. Nikolskaya, and, E. V. Koonin. 2001. Novel domains of the prokaryotic two-component signal transduction systems. FEMS Microbiol. Lett. 203:1121.
27. Gjermansen, M.,, P. Ragas, and, T. Tolker-Nielsen. 2006. Proteins with GGDEF and EAL domains regulate Pseudomonas putida biofilm formation and dispersal. FEMS Microbiol. Lett. 265:215224.
28. Goller, C.,, X. Wang,, Y. Itoh, and, T. Romeo. 2006. The cation-responsive protein NhaR of Escherichia coli activates pgaABCD transcription, required for production of the biofilm adhesin poly-β-1,6-N-acetyl-D-glucosamine. J. Bacteriol. 188:80228032.
29. Goller, C. C.,, A. Pannuri,, T. Romeo,, Y. Itoh, and, K. Suzuki. 2008. PGA accumulation and biofilm formation in Escherichia coli: modulation by c-di-GMP, abstr. H-057, p. 293. Abstr. 108th Gen. Meet. Am. Soc. Microbiol., Boston, MA.
30. Goodman, A. L.,, B. Kulasekara,, A. Rietsch,, D. Boyd,, R. S. Smith, and, S. A. Lory. 2004. A signaling network reciprocally regulates genes associated with acute infection and chronic persistence in Pseudomonas aeruginosa. Dev. Cell 7:745754.
31. Götz, F. 2002. Staphylococcus and biofilms. Mol. Microbiol. 43:13671378.
32. Gualdi, L.,, L. Tagliabue,, S. Bertagnoli,, T. Ieranó,, C. De Castro, and, P. Landini. 2008. Cellulose modulates biofilm formation by counteracting curli-mediated colonization of solid surfaces in Escherichia coli. Microbiology 154:20172024.
33. Gudapaty, S.,, K. Suzuki,, X. Wang,, P. Babitzke, and, T. Romeo. 2001. Regulatory interactions of Csr components: the RNA binding protein CsrA activates csrB transcription in Escherichia coli. J. Bacteriol. 183:60176027.
34. Gutierrez, P.,, Y. Li,, M. J. Osborne,, E. Pomerantseva,, Q. Liu, and, K. Gehring. 2005. Solution structure of the carbon storage regulator protein CsrA from Escherichia coli. J. Bacteriol. 187:34963501.
35. Heeb, S.,, S. A. Kuehne,, M. Bycroft,, S. Crivii,, M. D. Allen,, D. Haas,, M. Camara, and, P. Williams. 2006. Functional analysis of the post-transcriptional regulator RsmA reveals a novel RNA-binding site. J. Mol. Biol. 355:10261036.
36. Hengge, R. 2008. The two-component network and the general stress sigma factor RpoS (σs)in Escherichia coli. Adv. Exp. Med. Biol. 631:4053.
37. Hengge-Aronis,, R., and, D. Fischer. 1992. Identification and molecular analysis of glgS, a novel growth-phase-regulated and rpoS-dependent gene involved in glycogen synthesis in Escherichia coli. Mol. Microbiol. 6:18771886.
38. Heroven, A. K.,, K. Boühme,, M. Rohde, and, P. Dersch. 2008. A Csr-type regulatory system, including small non-coding RNAs, regulates the global virulence regulator RovA of Yer-sinia pseudotuberculosis through RovM. Mol. Microbiol. 68:11791195.
39. 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.
40. Himpsl, S. D.,, C. V. Lockatell,, J. R. Hebel,, D. E. Johnson, and, H. L. Mobley. 2008. Identification of virulence determinants in uropathogenic Proteus mirabilis using signature-tagged mutagenesis. J. Med. Microbiol. 57:10681078.
41. Hinnebusch, B. J., and, D. L. Erickson. 2008. Yersinia pestis biofilm in the flea vector and its role in the transmission of plague. Curr. Top. Microbiol. Immunol. 322:229248.
42. Holland, L. M.,, S. T. O’Donnell,, D. A. Ryjenkov,, L. Gomelsky,, S. R. Slater,, P. D. Fey,, M. Gomelsky, and, J. P. O’Gara. 2008. A staphylococcal GGDEF domain protein regulates biofilm formation independently of cyclic dimeric GMP. J. Bacteriol. 190:51785189.
43. Itoh, Y.,, J. D. Rice,, C. Goller,, A. Pannuri,, J. Taylor,, J. Meisner,, T. J. Beveridge,, J. F. Preston III, and, T. Romeo. 2008. Roles of pgaABCD genes in synthesis, modification, and export of the Escherichia coli biofilm adhesin poly-β-1,6-N-acetyl-D-glucosamine. J. Bacteriol. 190:36703680.
44. Itoh, Y.,, X. Wang,, B. J. Hinnebusch,, J. F. Preston III, and, T. Romeo. 2005. Depolymerization of β-1,6-N-acetyl-D-glucosamine disrupts the integrity of diverse bacterial biofilms. J. Bacteriol. 187:382387.
45. Izano, E. A.,, I. Sadovskaya,, E. Vinogradov,, M. H. Mulks,, K. Velliyagounder,, C. Ragunath,, W. B. Kher,, N. Ramasubbu,, S. Jabbouri,, M. B. Perry, and, J. B. Kaplan. 2007. Poly-N-acetylglucosamine mediates biofilm formation and antibiotic resistance in Actinobacillus pleuropneumoniae. Microb. Pathog. 43:19.
46. Jackson, D. W.,, J. W. Simecka, and, T. Romeo. 2002. Catabolite repression of Escherichia coli biofilm formation. J. Bacteriol. 184:34063410.
47. Jackson, D. W.,, K. Suzuki,, L. Oakford,, J. W. Simecka,, M. E. Hart, and, T. Romeo. 2002. Biofilm formation and dispersal under the influence of the global regulator CsrA of Escherichia coli. J. Bacteriol. 184:290301.
48. Jenal, U., and, J. Malone. 2006. Mechanisms of cyclic-di-GMP signaling in bacteria. Annu. Rev. Genet. 40:385407.
49. Jonas, K.,, A. N. Edwards,, R. Simm,, T. Romeo,, U. Roümling, 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.
50. Jones, M. K.,, E. B. Warner, and, J. D. Oliver. 2008. csrA inhibits the formation of biofilms by Vibrio vulnificus. Appl. Environ. Microbiol. 74:70647066.
51. Kay, E.,, C. Dubuis, and, D. Haas. 2005. Three small RNAs jointly ensure secondary metabolism and biocontrol in Pseudomonas fluorescens CHA0. Proc. Natl. Acad. Sci. USA 102:1713617141.
52. 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. 189:81658178.
53. Kumar, M., and, D. Chatterji. 2008. Cyclic di-GMP: a second messenger required for long-term survival, but not for biofilm formation, in Mycobacterium smegmatis. Microbiology 154:29422955.
54. Kushner, S. R. 2002. mRNA decay in Escherichia coli comes of age. J. Bacteriol. 184:46584665.
55. Lapouge, K.,, M. Schubert,, F. H. Allain, and, D. Haas. 2008. Gac/Rsm signal transduction pathway of gamma-Proteobacteria: from RNA recognition to regulation of social behaviour. Mol. Microbiol. 67:241253.
56. 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. 65:14741484.
57. Lenz, D. H.,, M. B. Miller,, J. Zhu,, R. V. Kulkarni, and, B. L. Bassler. 2005. CsrA and three redundant small RNAs regulate quorum sensing in Vibrio cholerae. Mol. Microbiol. 58:11861202.
58. Liu, M. Y.,, G. Gui,, B. Wei,, J. F. Preston III,, L. Oakford,, U. Yuksel,, D. P. Giedroc, and, T. Romeo. 1997. The RNA molecule CsrB binds to the global regulatory protein CsrA and antagonizes its activity in Escherichia coli. J. Biol. Chem. 272:1750217510.
59. Liu, M. Y., and, T. Romeo. 1997. The global regulator CsrA of Escherichia coli is a specific mRNA-binding protein. J. Bacteriol. 179:46394642.
60. Liu, M. Y.,, H. Yang, and, T. Romeo. 1995. The product of the pleiotropic Escherichia coli gene csrA modulates glycogen biosynthesis via effects on mRNA stability. J. Bacteriol. 177:26632672.
61. Lucchetti-Miganeh,, C.,, E. Burrowes,, C. Baysse, and, G. Ermel. 2008. The post-transcriptional regulator CsrA plays a central role in the adaptation of bacterial pathogens to different stages of infection in animal hosts. Microbiology 154:1629.
62. Majdalani, N.,, C. K. Vanderpool, and, S. Gottesman. 2005. Bacterial small RNA regulators. Crit. Rev. Biochem. Mol. Biol. 40:93113.
63. May, T., and, S. Okabe. 2008. Escherichia coli harboring a natural IncF conjugative F plasmid develops complex mature biofilms by stimulating synthesis of colanic acid and curli. J. Bacteriol. 190:74797490.
64. Mercante, J.,, K. Suzuki,, X. Cheng,, P. Babitzke, and, T. Romeo. 2006. Comprehensive alanine-scanning mutagenesis of Escherichia coli CsrA defines two subdomains of critical functional importance. J. Biol. Chem. 281:3183231842.
65. Molofsky, A. B., and, S. Swanson. 2004. Differentiate to thrive: lessons from the Legionella pneumophila life cycle. Mol. Microbiol. 53:2940.
66. Mondragon, V.,, B. Franco,, K. Jonas,, K. Suzuki,, T. Romeo,, O. Melefors, and, D. Georgellis. 2006. pH dependent activation of the BarA-UvrY two-component system in Escherichia coli. J. Bacteriol. 188:83038306.
67. Morgan, R.,, S. Kohn,, S. H. Hwang,, D. J. Hassett, and, K. Sauer. 2006. BdlA, achemotaxis regulator essential for biofilm dispersion in Pseudomonas aeruginosa. J. Bacteriol. 188:73357343.
68. Mukhopadhyay, S.,, J. P. Audia,, R. N. Roy, and, H. E. Schellhorn. 2000. Transcriptional induction of the conserved alternative sigma factor RpoS in Escherichia coli is dependent on BarA, a probable two-component regulator. Mol. Microbiol. 37:371381.
69. Mulcahy, H.,, J. O’Callaghan,, E. P. O’Grady,, M. D. Macia,, N. Borrell,, C. Gómez,, P. G. Casey,, C. Hill,, C. Adams,, C. G. Gahan,, A. Oliver, and, F. O’Gara. 2008. Pseudomonas aeruginosa RsmA plays an important role during murine infection by influencing colonization, virulence, persistence, and pulmonary inflammation. Infect. Immun. 76:632638.
70. Nakhamchik, A.,, C. Wilde, and, D. A. Rowe-Magnus. 2008. Cyclic-di-GMP regulates extracellular polysaccharide production, biofilm formation, and rugose colony development by Vibrio vulnificus. Appl. Environ. Microbiol. 74:41994209.
71. 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.
72. Parise, G.,, M. Mishra,, Y. Itoh,, T. Romeo, and, R. Deora. 2007. Role of a putative polysaccharide locus in Bordetella biofilm development. J. Bacteriol. 189:750760.
73. Pernestig, A. K.,, D. Georgellis,, T. Romeo,, K. Suzuki,, H. Tomenius,, S. Normark, and, O. Melefors. 2003. The Escherichia coli BarA-UvrY two-component system is needed for efficient switching between glycolytic and gluconeogenic carbon sources. J. Bacteriol. 185:843853.
74. Pesavento, C.,, G. Becker,, N. Sommerfeldt,, A. Possling,, N. Tschowri,, A. Mehlis, and, R. Hengge. 2008. Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli. Genes Dev. 22:24342446.
75. Prigent-Combaret,, C.,, E. Brombacher,, O. Vidal,, A. Ambert,, P. Lejeune,, P. Landini, and, C. Dorel. 2001. Complex regulatory network controls initial adhesion and biofilm formation in Escherichia coli via regulation of the csgD gene. J. Bacteriol. 183:72137223.
76. Rand, J. D.,, S. G. Danby,, D. L. Greenway, and, R. R. England. 2002. Increased expression of the multidrug efflux genes acrAB occurs during slow growth of Escherichia coli. FEMS Microbiol. Lett. 207:9195.
77. Reimmann, C.,, C. Valverde,, E. Kay, and, D. Haas. 2005. Post-transcriptional repression of GacS/GacA-controlled genes by the RNA-binding protein RsmE acting together with RsmA in the biocontrol strain Pseudomonas fluorescens CHA0. J. Bacteriol. 187:276285.
78. Rife, C.,, R. Schwarzenbacher,, D. McMullan,, P. Abdubek,, E. Ambing,, H. Axelrod,, T. Biorac,, J. M. Canaves,, H. J. Chiu,, A. M. Deacon,, M. DiDonato,, M. A. Elsliger,, A. Godzik,, C. Grittini,, S. K. Grzechnik,, J. Hale,, E. Hampton,, G. W. Han,, J. Haugen,, M. Hornsby,, L. Jaroszewski,, H. E. Klock,, E. Koesema,, A. Kreusch,, P. Kuhn,, S. A. Lesley,, M. D. Miller,, K. Moy,, E. Nigoghossian,, J. Paulsen,, K. Quijano,, R. Reyes,, E. Sims,, G. Spraggon,, R. C. Stevens,, H. van den Bedem,, J. Velasquez,, J. Vincent,, A. White,, G. Wolf,, Q. Xu,, K. L. O. Hodgson,, J. Wooley, and, I. A. Wilson. 2005. Crystal structure of the global regulatory protein CsrA from Pseudomonas putida at 2.05 A resolution reveals a new fold. Proteins 61:449453.
79. Romeo, T. 1998. Global regulation by the small RNA-binding protein CsrA and the non-coding RNA molecule CsrB. Mol. Microbiol. 29:13211330.
80. Romeo, T.,, J. Black, and, J. Preiss. 1990. Genetic regulation of glycogen biosynthesis in Escherichia coli: in vivo effects of the catabolite repression and stringent response systems. Curr. Microbiol. 21:131137.
81. Romeo, T.,, M. Gong,, M. Y. Liu, and, A. M. BrunZinkernagel. 1993. Identification and molecular characterization of csrA, a pleiotropic gene from Escherichia coli that affects glycogen biosynthesis, gluconeogenesis, cell size, and surface properties. J. Bacteriol. 175:47444755.
82. Romeo, T.,, J. Moore, and, J. Smith. 1991. A simple method for cloning genes involved in glucan biosynthesis: application to the isolation of structural and regulatory genes for glycogen synthesis in Escherichia coli. Gene 108:2329.
83. Romeo, T., and, J. Preiss. 1989. Genetic regulation of glycogen biosynthesis in Escherichia coli: in vitro effects of cyclic AMP and guanosine 5′-diphosphate 3′-diphosphate and analysis of in vivo transcripts. J. Bacteriol. 171:27732782.
84. Römling, U. 2005. Characterization of the rdar morphotype, a multicellular behaviour in Enterobacteriaceae. Cell. Mol. Life Sci. 62:12341246.
85. Römling, U., and, D. Amikam. 2006. Cyclic di-GMP as a second messenger. Curr. Opin. Microbiol. 9:218228.
86. Römling, U.,, M. Gomelsky, and, M. Y. Galperin. 2005. C-di-GMP: the dawning of a novel bacterial signalling system. Mol. Microbiol. 57:629639.
87. Ross, P.,, H. Weinhouse,, Y. Aloni,, D. Michaeli,, P. Weinberger-Ohana,, R. Mayer,, S. Braun,, E. de Vroom,, G. A. van der Marel,, J. H. van Boom, and, M. Benziman. 1987. Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature 325:279281.
88. Ryjenkov, D. A.,, R. Simm,, U. Römling, and, M. Gomelsky. 2006. The PilZ domain is a receptor for the second messenger c-di-GMP: the PilZ domain protein YcgR controls motility in enterobacteria. J. Biol. Chem. 281:3031030314.
89. Sabnis, N. A.,, H. Yang, and, T. Romeo. 1995. Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA. J. Biol. Chem. 270:2909629104.
90. 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. 187:47744781.
91. Schubert, M.,, K. Lapouge,, O. Duss,, F. C. Oberstrass,, I. Jelesarov,, D. Haas, and, F. H. Allain. 2007. Molecular basis of messenger RNA recognition by the specific bacterial repressing clamp RsmA/CsrA. Nat. Struct. Mol. Biol. 14:807813.
92. Simm, R.,, M. Morr,, A. Kader,, M. Nimtz, and, U. Römling. 2004. GGDEF and EAL domains inversely regulate cyclic di-GMP levels and transition from sessility to motility. Mol. Microbiol. 53:11231134.
93. Sommerfeldt, N.,, A. Possling,, G. Becker,, C. Pesavento,, N. Tschowri, and, R. Hengge. 2009. Gene expression patterns and differential input into curli fimbriae regulation of all GGDEF/EAL domain proteins in Escherichia coli. Microbiology 155:13181331. [Epub ahead of print.]
94. Sudarsan, N.,, E. R. Lee,, Z. Weinberg,, R. H. Moy,, J. N. Kim,, K. H. Link, and, R. R. Breaker. 2008. Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321:411413.
95. Suzuki, K.,, P. Babitzke,, S. R. Kushner, and, T. Romeo. 2006. Identification of a novel regulatory protein (CsrD) that targets the global regulatory RNAs CsrB and CsrC for degradation by RNase E. Genes Dev. 20:26052617.
96. Suzuki, K.,, X. Wang,, T. Weilbacher,, A. K. Pernestig,, Oü. Melefors,, D. Georgellis,, P. Babitzke, and, T. Romeo. 2002. Regulatory circuitry of the CsrA/CsrB and BarA/UvrY systems of Escherichia coli. J. Bacteriol. 184:51305140.
97. Tamayo, R.,, J. T. Pratt, and, A. Camilli. 2007. Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu. Rev. Microbiol. 61:131148.
98. Tamayo, R.,, A. D. Tischler, and, A. Camilli. 2005. The EAL domain protein VieA is a cyclic diguanylate phosphodiesterase. J. Biol. Chem. 280:3332433330.
99. 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.
100. Teplitski, M.,, A. Al-Agely, and, B. M. Ahmer. 2006. Contribution of the SirA regulon to biofilm formation in Salmonella enterica serovar Typhimurium. Microbiology 152:34113424.
101. Teplitski, M.,, R. I. Goodier, and, B. M. Ahmer. 2006. Catabolite repression of the SirA regulatory cascade in Salmonella enterica. Intl. J. Med. Microbiol. 296:449466.
102. Thormann, K. M.,, S. Duttler,, R. M. Saville,, M. Hyodo,, S. Shukla,, Y. Hayakawa, and, A. M. Spormann. 2006. Control of formation and cellular detachment from Shewanella onei-densis MR-1 biofilms by cyclic di-GMP. J. Bacteriol. 188:26812691.
103. Toledo-Arana,, A.,, F. Repoila, and, P. Cossart. 2007. Small noncoding RNAs controlling pathogenesis. Curr. Opin. Microbiol. 10:182188.
104. Tschowri, N.,, S. Bussy, and, R. Hengge. 2009. The BLUF-EAL protein YcgF acts as a direct anti-repressor in a blue-light response of Escherichia coli. Genes Dev. 23:522534.
105. Updegrove, T.,, N. Wilf,, X. Sun, and, R. M. Wartell. 2008. Effect of Hfq on RprA-rpoS mRNA pairing: Hfq-RNA binding and the influence of the 5′ rpoS mRNA leader region. Biochemistry 47:1118411195.
106. Valverde, C.,, M. Lindell,, E. G. H. Wagner, and, D. Haas. 2004. A repeated GGA motif is critical for the activity and stability of the riboregulator RsmY of Pseudomonas fluorescens. J. Biol. Chem. 279:2506625074.
107. Van Houdt,, R.,, A. Aertsen,, P. Moons,, K. Vanoirbeek, and, C. W. Michiels. 2006. N-acyl-l-homoserine lactone signal interception by Escherichia coli. FEMS Microbiol. Lett. 256:8389.
108. 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.
109. Wang, X.,, J. F. Preston III, and, T. Romeo. 2004. The pgaABCD locus of Escherichia coli promotes the synthesis of a polysaccharide adhesin required for biofilm formation. J. Bacteriol. 186:27242734.
110. Weber, H.,, C. Pesavento,, A. Possling,, G. Tischendorf, and, R. Hengge. 2006. Cyclic-di-GMP-mediated signalling within the sigma network of Escherichia coli. Mol. Microbiol. 62:10141034.
111. Wei, B. L.,, A. M. Brun-Zinkernagel,, J. W. Simecka,, B. M. Prüip,, P. Babitzke, and, T. Romeo. 2001. Positive regulation of motility and flhDC expression by the RNA-binding protein CsrA of Escherichia coli. Mol. Microbiol. 40:245256.
112. Wei, B. L.,, S. Shin,, D. LaPorte,, A. J. Wolfe, and, T. Romeo. 2000. Global regulatory mutations in csrA and rpoS cause severe central carbon stress in Escherichia coli in the presence of acetate. J. Bacteriol. 182:16321640.
113. Weilbacher, T.,, K. Suzuki,, A. K. Dubey,, X. Wang,, S. Gudapaty,, I. Morozov,, C. S. Baker,, D. Georgellis,, P. Babitzke, and, T. Romeo. 2003. A novel sRNA component of the carbon storage regulatory system of Escherichia coli. Mol. Microbiol. 48:657670.
114. Weinberg, Z.,, J. E. Barrick,, Z. Yao,, A. Roth,, J. N. Kim,, J. Gore,, J. X. Wang,, E. R. Lee,, K. F. Block,, N. Sudarsan,, S. Neph,, M. Tompa,, W. L. Ruzzo, and, R. R. Breaker. 2007. Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline. Nucleic Acids Res. 35:48094819.
115. 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. 416:207211.
116. White, D.,, M. E. Hart, and, T. Romeo. 1996. Phylogenetic distribution of the regulatory gene csrA among Eubacteria. Gene 182:221223.
117. Wolfe, A. J., and, K. L. Visick. 2008. Get the message out: cyclic-di-GMP regulates multiple levels of flagellum-based motility. J. Bacteriol. 190:463475.
118. Yakhnin, H.,, P. Pandit,, T. J. Petty,, C. S. Baker,, T. Romeo, and, P. Babitzke. 2007. CsrA of Bacillus subtilis regulates translation initiation of the gene encoding the flagellin protein (hag) by blocking ribosome binding. Mol. Microbiol. 64:16051620.
119. Yang, H.,, M. Y. Liu, and, T. Romeo. 1996. Coordinate genetic regulation of glycogen catabolism and biosynthesis in Escherichia coli via the CsrA gene product. J. Bacteriol. 178:10121017.

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