Source: http://www.asmscience.org/content/book/10.1128/9781555816667.ch08
Timestamp: 2019-04-20 02:27:25+00:00

Document:
Influence of c-di-GMP in controlling the transition from the planktonic to biofilm lifestyle and vice versa. DGC enzymes make c-di-GMP, while its breakdown is mediated by either PDE or HD-GYP activity. The observation that many mutants in the genes that encode DGC and PDE of HD-GYP enzymes result in pleiotropic or incomplete phenotypes suggests that cells use c-di-GMP concentrations ([c-di-GMP]) as a means to measure when it is optimal to fully commit to either lifestyle. As a result, there is a level of c-di-GMP where both planktonic and biofilm traits can still be functional (overlapping circles). Only once the thresholds of this intersection have been passed will a cell commit to either lifestyle.
Diagram showing the different stages of P. aeruginosa biofilm formation that are influenced by c-di-GMP (indicated by the stars). Elevated c-di-GMP promotes initial attachment, which involves adherence of free-swimming cells to a surface. In the case of a flat biofilm, cells continue to multiply and move on the surface, forming a confluent, flat mat of cells. In the case of structured biofilms, we present two alternative routes to their formation. The first we call structured biofilm I. Here, dark gray cells represent the immobile stalks of structured biofilms, while light gray cells represent the motile subpopulation that produce the cap. The second we call structured biofilm II. In both cases, the structured biofilms are characterized by EPS production (either Pel, Psl, or alginate, depending upon the strain). EPS production is promoted by elevated c-di-GMP. In this case, small cell aggregates grow clonally, forming large cell aggregates consisting of cells primarily derived from cells in the small cell aggregates. This is indicated by the large aggregate of dark gray cells in the figure, indicating that the cells in the aggregate are progeny derived from the initial small aggregates. Finally, cells can actively leave the biofilm to reinitiate the cycle in a process called dispersion or detachment. c-di-GMP has also been implicated in this step.
Schematic diagram depicting the alginate biosynthetic machinery. c-di-GMP binds the PilZ domain of Alg44, acting as a positive allosteric activator. Alg8 and Alg44, inner membrane (I.M.) proteins; K (AlgK), periplasmic lipoprotein with lipid anchor in the outer membrane (O.M.) and a tetratricopeptide repeat scaffold protein; E (AlgE), outer membrane porin-like protein that interacts with AlgK; G (AlgG), periplasmic protein that has a right-handed beta-helical domain and contains the epimerase active site; L (AlgL), a periplasmic protein likely involved in alginate processing; F (AlgF), periplasmic protein; J (AlgJ), periplasmic protein anchored in the inner membrane by a noncleaved signal peptide; I (AlgI), inner membrane protein with seven membrane-spanning domains; X (AlgX), periplasmic protein (function not known yet).
c-di-GMP controls Pel production at two levels. (A) Schematic depicting the predicted localization of the Pel bio-synthetic machinery. The localization is primarily based upon bioinformatics, except in the case of PelC, which has been shown experimentally to localize to the outer membrane. c-di-GMP acts as an allosteric activator of PelD. The Pel proteins are predicted to have the following functions. PelA is a large soluble, periplasmic protein with no clear function; it has a large amount of disorder but may adopt a TIM barrel structure. PelB is an outer membrane protein with a large N-terminal TPR domain followed by a C-terminal porin domain. PelC is an outer membrane lipoprotein that may adopt a TolB-like structure. PelD is a cytoplasmic membrane protein with four transmembrane helices (TMs) that has a c-di-GMP binding domain. PelE is a cytoplasmic membrane protein with two TMs followed by a periplasmic region (residues 90 to 320) carrying four or five TPR motifs (residues 155 to 310). Residues 90 to 150 are predicted to carry loops and helices; residues ∼115 to 127 may be disordered. PelF is a cytoplasmic glycosyltransferase. PelG is a cytoplasmic membrane protein with 12 TMs that is a member of the polysaccharide transporter family and also resembles Na+/H+ antiporters. (B) c-di-GMP also binds to the transcriptional repressor FleQ. When c-di-GMP levels are low, FleQ represses pel expression (left). At elevated levels, c-di-GMP binds FleQ, relieving repression of pel expression (right).
Contrasting patterns of flagellum-mediated swimming and swarming used to exemplify the difference between these two modes of movement. (A) Salmonella enterica serovar Typhimurium exhibiting flagellum-mediated swimming and swarming; (B) Pseudomonas aeruginosa. Motility assays for swimming are performed using 0.3% agar while swarming assays utilize between 0.5 and 0.7% agar. On 0.3% agar, the resulting swarm is of a uniform diameter containing characteristic rings embedded within the agar matrix. These rings are waves of bacteria utilizing chemotaxis to alternative nutrients in the medium. In contrast, swarms produced on 0.5 to 0.7% agar are much more spectacular in shape and diameter.
Schematic diagram of the type IV pilus and the assembly and retraction cycles mediated by the two ATPases PilB and PilT. The six major components are not all depicted in the structure for clarity, and the inner membrane anchor PilD and the proposed secretin PilQ are labeled. The models for assembly and retraction reflect the proposed models of Craig and Li ( 21 ) (assembly) and Kaiser ( 61 ) (retraction). An underlying principle of both cycles is that pilin subunits can be stored in the inner membrane until needed. The control of pilus assembly by c-di-GMP through PilZ is highlighted. The gray arrows indicate alternative routes for c-di-GMP regulation of the process, most of which require further investigation.
Schematic diagram comparing the coordination of flagellar gene expression and assembly when one or two assembly checkpoints are used. The important structural features of the flagellum are highlighted. One checkpoint: this pathway is utilized by the paradigm flagellar systems of E. coli and S. enterica serovar Typhimurium. The master regulator FlhD4C2 activates P class2 in conjunction with σ70. This promoter class drives the expression of the HBB structural components and several regulatory proteins, including σ28 and FlgM. Upon HBB completion, FlgM is secreted, allowing σ28 to initiate transcription from Pclass3. Two checkpoints: one example of this pathway is that used by P. aeruginosa. Here proximal basal body gene expression is activated by the atypical σ 54 EBP, FleQ. A second σ 54 EBP recognizes the initiation of T3S/rod assembly, activating transcription of genes that encode the distal HBB structural components and a number of other regulatory components. For P. aeruginosa, HBB completion is sensed in a similar manner to that of E. coli that results in σ 28 activating flagellin gene expression. In C. crescentus, this checkpoint is coupled to flagellin translation, not transcription, as an added twist. Note, C. crescentus does not utilize a FleQ homologue to activate its transcription hierarchy but does utilize a σ54 EBP2 sensory system to coordinate distal basal body gene expression and assembly. Txn., transcription; Tln., translation.
Summary of the multiple targets during flagellar assembly influenced by c-di-GMP regulation. (Gray box) Flagellar rotation is negatively controlled by the homologues YcgR and DgrA in E. coli (ec) and C. crescentus (cc), respectively. Flagellar assembly in C. crescentus and V. fischeri (vf) is controlled at a posttranscriptional level during HBB assembly, potentially to control the Mot−-to-Mot+ transition. A direct role for c-di-GMP has been shown for the P. aeruginosa flagellar master regulator FleQ (see Fig. 3 ).
1. Aldridge, P., and, K. T. Hughes. 2001. How and when are substrates selected for type III secretion? Trends Microbiol. 9: 209– 214.
2. Aldridge, P., and, K. T. Hughes. 2002. Regulation of flagellar assembly. Curr. Opin. Microbiol. 5: 160– 165.
4. Allison, C., and, C. Hughes. 1991. Bacterial swarming: an example of prokaryotic differentiation and multicellular behaviour. Sci. Prog. 75: 403– 422.
5. Alm, R. A.,, J. P. Hallinan,, A. A. Watson, and, J. S. Mattick. 1996. Fimbrial biogenesis genes of Pseudomonas aeruginosa: pilW and pilX increase the similarity of type 4 fimbriae to the GSP protein-secretion systems and pilY1 encodes a gonococcal PilC homologue. Mol. Microbiol. 22: 161– 173.
6. Altmann, D.,, P. Stief,, R. Amann,, D. de Beer, and, A. Schramm. 2003. In situ distribution and activity of nitrifying bacteria in freshwater sediment. Environ. Microbiol. 5: 798– 803.
7. 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: 5574– 5581.
8. Banin, E.,, M. L. Vasil, and, E. P. Greenberg. 2005. Iron and Pseudomonas aeruginosa biofilm formation. Proc. Natl. Acad. Sci. USA 102: 11076– 11081.
9. Berg, H. C. 2008. Bacterial flagellar motor. Curr. Biol. 18: R689– R691.
10. Berg, H. C. 2003. The rotary motor of bacterial flagella. Annu. Rev. Biochem. 72: 19– 54.
11. Berg, H. C., and, R. A. Anderson. 1973. Bacteria swim by rotating their flagellar filaments. Nature 245: 380– 382.
12. Bomchil, N.,, P. Watnick, and, R. Kolter. 2003. Identification and characterization of a Vibrio cholerae gene, mbaA, involved in maintenance of biofilm architecture. J. Bacteriol. 185: 1384– 1390.
13. Buck, M.,, M. T. Gallegos,, D. J. Studholme,, Y. Guo, and, J. D. Gralla. 2000. The bacterial enhancer-dependent σ 54 (σ N) transcription factor. J. Bacteriol. 182: 4129– 4136.
14. Burrows, L. L. 2005. Weapons of mass retraction. Mol. Microbiol. 57: 878– 888.
16. Chilcott, G., and, K. T. Hughes. 2000. Coupling of flagellar gene expression to flagellar assembly in Salmonella enterica serovar Typhimurium and Escherichia coli. Microbiol. Mol. Biol. Rev. 64: 694– 708.
17. Christen, M.,, B. Christen,, M. G. Allan,, M. Folcher,, P. Jeno,, S. Grzesiek, and, U. Jenal. 2007. DgrA is a member of a new family of cyclic diguanosine monophosphate receptors and controls flagellar motor function in Caulobacter crescentus. Proc. Natl. Acad. Sci. USA 104: 4112– 4117.
18. Clegg, S., and, K. T. Hughes. 2002. FimZ is a molecular link between sticking and swimming in Salmonella enterica serovar Typhimurium. J. Bacteriol. 184: 1209– 1213.
19. Costerton, J. W.,, Z. Lewandowski,, D. E. Caldwell,, D. R. Korber, and, H. M. Lappin-Scott. 1995. Microbial biofilms. Annu. Rev. Microbiol. 49: 711– 745.
20. Costerton, J. W.,, P. S. Stewart, and, E. P. Greenberg. 1999. Bacterial biofilms: a common cause of persistent infections. Science 284: 1318– 1322.
21. Craig, L., and, J. Li. 2008. Type IV pili: paradoxes in form and function. Curr. Opin. Struct. Biol. 18: 267– 277.
22. Danese, P. N.,, L. A. Pratt, and, R. Kolter. 2000. Exopolysaccharide production is required for development of Escherichia coli K-12 biofilm architecture. J. Bacteriol. 182: 3593– 3596.
23. 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.
24. Darnton, N. C.,, L. Turner,, S. Rojevsky, and, H. C. Berg. 2007. On torque and tumbling in swimming Escherichia coli. J. Bacteriol. 189: 1756– 1764.
25. 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 c 70 dependent and is downregulated by Vfr, a homolog of Escherichia coli cyclic AMP receptor protein. J. Bacteriol. 184: 5240– 5250.
26. 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.
27. Davey, M. E.,, N. C. Caiazza, and, G. A. O’Toole. 2003. Rhamnolipid surfactant production affects biofilm architecture in Pseudomonas aeruginosa PAO1. J. Bacteriol. 185: 1027– 1036.
28. de Kievit,, T. R. 2009. Quorum sensing in Pseudomonas aeruginosa biofilms. Environ. Microbiol. 11: 279– 288.
29. Fletcher, M., and, G. Floodgate. 1973. An electron-microscopic demonstration of an acidic polysaccharide involved in the adhesion of a marine bacterium to solid surfaces. J. Gen. Microbiol. 74: 325– 334.
30. Fraser, G. M., and, C. Hughes. 1999. Swarming motility. Curr. Opin. Microbiol. 2: 630– 635.
31. Friedman, L., and, R. Kolter. 2004. Genes involved in matrix formation in Pseudomonas aeruginosa PA14 biofilms. Mol. Microbiol. 51: 675– 690.
32. Friedman, L., and, R. Kolter. 2004. Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aerguinosa biofilm matrix. J. Bacteriol. 186: 4457– 4465.
33. Furukawa, S.,, S. L. Kuchma, and, G. A. O’Toole. 2006. Keeping their options open: acute versus persistent infections. J. Bacteriol. 188: 1211– 1217.
34. 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.
35. Gilbert, P.,, P. J. Collier, and, M. R. Brown. 1990. Influence of growth rate on susceptibility to antimicrobial agents: biofilms, cell cycle, dormancy, and stringent response. Antimicrob. Agents Chemother. 34: 1865– 1868.
36. Gillen, K. L., and, K. T. Hughes. 1991. Negative regulatory loci coupling flagellin synthesis to flagellar assembly in Salmonella typhimurium. J. Bacteriol. 173: 2301– 2310.
37. 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: 894– 906.
38. 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: 215– 224.
39. Gober, J. W.,, J. C. England,, Y. Brun, and, L. J. Schimkets. 2000. Regulation of flagellum biosynthesis and motility in Caulobacter, p. 319-399. In Y. Brun (ed.) Prokaryotic Development. ASM Press, Washington, DC.
40. Gomez-Suarez,, C.,, J. Pasma,, A. J. van der Borden,, J. Wingender,, H.-C., Flemming,, H. J. Busscher, and, H. C. van der Mei. 2002. Influence of extracellular polymeric substances on deposition and redeposition of Pseudomonas aeruginosa to surfaces. Microbiology 148: 1161– 1169.
41. Govan, J. R., and, V. Deretic. 1996. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Rev. 60: 539– 574.
42. Gygi, D.,, M. M. Rahman,, H. C. Lai,, R. Carlson,, J. Guard-Petter, and, C. Hughes. 1995. A cell-surface polysaccharide that facilitates rapid population migration by differentiated swarm cells of Proteus mirabilis. Mol. Microbiol. 17: 1167– 1175.
43. Harshey, R. M. 2003. Bacterial motility on a surface: many ways to a common goal. Annu. Rev. Microbiol. 57: 249– 273.
44. Harshey, R. M. 1994. Bees aren’t the only ones: swarming in gram-negative bacteria. Mol. Microbiol. 13: 389– 394.
45. Hay, N. A.,, D. J. Tipper,, D. Gygi, and, C. Hughes. 1999. A novel membrane protein influencing cell shape and multicellular swarming of Proteus mirabilis. J. Bacteriol. 181: 2008– 2016.
46. Hentzer, M.,, G. M. Teitzel,, G. J. Balzer,, A. Heydorn,, S. Molin,, M. Givskov, and, M. R. Parsek. 2001. Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function. J. Bacteriol. 183: 5395– 5401.
47. Hickman, J., and, C. Harwood. 2008. Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor. Mol. Microbiol. 69: 376– 389.
48. 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.
49. 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: 905– 918.
50. Hoiby, N. 2006. P. aeruginosa in cystic fibrosis patients resists host defenses, antibiotics. Microbe 1: 571– 577.
51. Hughes, K. T.,, K. L. Gillen,, M. J. Semon, and, J. E. Karlinsey. 1993. Sensing structural intermediates in bacterial flagellar assembly by export of a negative regulator. Science 262: 1277– 1280.
52. Huitema, E.,, S. Pritchard,, D. Matteson,, S. K. Radhakrishnan, and, P. H. Viollier. 2006. Bacterial birth scar proteins mark future flagellum assembly site. Cell 124: 1025– 1037.
53. Ishihama, A. 1993. Protein-protein communication within the transcription apparatus. J. Bacteriol. 175: 2483– 2489.
54. Iyoda, S.,, T. Kamidoi,, K. Hirose,, K. Kutsukake, and, H. Watanabe. 2001. A flagellar gene fliZ regulates the expression of invasion genes and virulence phenotype in Salmonella enterica serovar Typhimurium. Microb. Pathog. 30: 81– 90.
55. Jackson, D. W.,, J. W. Simecka, and, T. Romeo. 2002. Catabolite repression of Escherichia coli biofilm formation. J. Bacteriol. 184: 3406– 3410.
56. 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.
57. Jarrell, K. F., and, M. McBride. 2008. The surprisingly diverse ways that prokaryotes move. Nat. Rev. Microbiol. 6: 466.
58. Jenal, U., and, J. Malone. 2006. Mechanisms of cyclic-di-GMP signaling in bacteria. Ann. Rev. Genet. 40: 385– 407.
59. Jyot, J.,, N. Dasgupta, and, R. Ramphal. 2002. FleQ, the major flagellar gene regulator in Pseudomonas aeruginosa, binds to enhancer sites located either upstream or atypically downstream of the RpoN binding site. J. Bacteriol. 184: 5251– 5260.
60. Kaiser, D. 2000. Bacterial motility: how do pili pull? Curr. Biol. 10: R777– R780.
61. Kaiser, D. 2007. Bacterial swarming: a re-examination of cell-movement patterns. Curr. Biol. 17: R561– R570.
62. Kanehisa, M.,, M. Araki,, S. Goto,, M. Hattori,, M. Hirakawa,, M. Itoh,, T. Katayama,, S. Kawashima,, S. Okuda,, T. Toki-matsu, and, Y. Yamanishi. 2008. KEGG for linking genomes to life and the environment. Nucleic Acids Res. 36: D480– D484.
63. Kanehisa, M.,, S. Goto,, S. Kawashima,, Y. Okuno, and, M. Hattori. 2004. The KEGG resource for deciphering the genome. Nucleic Acids Res. 32: D277– D280.
64. Kaneko, Y.,, M. Thoendel,, O. Olakanmi,, B. E. Britigan, and, P. K. Singh. 2007. The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J. Clin. Investig. 117: 877– 888.
65. Kearns, D. B.,, J. Robinson, and, L. J. Shimkets. 2001. Pseudomonas aeruginosa exhibits directed twitching motility up phosphatidylethanolamine gradients. J. Bacteriol. 183: 763– 767.
66. Kindaichi, T.,, T. Ito, and, S. Okabe. 2004. Ecophysiological interaction between nitrifying bacteria and heterotrophic bacteria in autotrophic nitrifying biofilms as determined by microautoradiography-fluorescence in situ hybridization. Appl. Environ. Microbiol. 70: 1641– 1650.
67. 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.
68. Klausen, M.,, A. Aaes-Jorgensen,, S. Molin, and, T. Tolker-Nielsen. 2003. Involvement of bacterial migration in the development of complex multicellular structures in Pseudomonas aeruginosa biofilms. Mol. Microbiol. 50: 61– 68.
69. Klausen, M.,, A. Heydorn,, P. Ragas,, L. Lambertsen,, A. Aaes-Jorgensen,, S. Molin, and, T. Tolker-Nielsen. 2003. Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutants. Mol. Microbiol. 48: 1511– 1524.
70. Koga, T.,, K. Ishimoto, and, S. Lory. 1993. Genetic and functional characterization of the gene cluster specifying expression of Pseudomonas aeruginosa pili. Infect. Immun. 61: 1371– 1377.
71. Kojima, S., and, D. F. Blair. 2004. The bacterial flagellar motor: structure and function of a complex molecular machine. Int. Rev. Cytol. 233: 93– 134.
72. Kolenbrander, P. E.,, R. N. Andersen,, D. S. Blehert,, P. G. Egland,, J. S. Foster, and R. J. Palmer, Jr. 2002. Communication among oral bacteria. Microbiol. Mol. Biol. Rev. 66: 486– 505.
73. Kulasakara, 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.
74. Kutsukake, K.,, Y. Ohya, and, T. Iino. 1990. Transcriptional analysis of the flagellar regulon of Salmonella typhimurium. J. Bacteriol. 172: 741– 747.
75. Landry, R. M.,, D. An,, J. T. Hupp,, P. K. Singh, and, M. R. Parsek. 2006. Mucin- Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance. Mol. Microbiol. 59: 142– 151.
76. Lanois, A.,, G. Jubelin, and, A. Givaudan. 2008. FliZ, a flagellar regulator, is at the crossroads between motility, haemolysin expression and virulence in the insect pathogenic bacterium Xenorhabdus. Mol. Microbiol. 68: 516– 533.
77. 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.
78. Lequette, Y., and, E. P. Greenberg. 2005. Timing and localization of rhamnolipid synthesis gene expression in Pseudomonas aeruginosa biofilms. J. Bacteriol. 187: 37– 44.
79. Liu, X.,, N. Fujita,, A. Ishihama, and, P. Matsumura. 1995. The C-terminal region of the alpha subunit of Escherichia coli RNA polymerase is required for transcriptional activation of the flagellar level II operons by the FlhD/FlhC complex. J. Bacteriol. 177: 5186– 5188.
80. Llewellyn, M.,, R. J. Dutton,, J. Easter,, D. O’donnol, and, J. W. Gober. 2005. The conserved flaF gene has a critical role in coupling flagellin translation and assembly in Caulobacter crescentus. Mol. Microbiol. 57: 1127– 1142.
81. Lucas, R. L.,, C. P. Lostroh,, C. C. DiRusso,, M. P. Spector,, B. L. Wanner, and, C. A. Lee. 2000. Multiple factors independently regulate hilA and invasion gene expression in Salmonella enterica serovar Typhimurium. J. Bacteriol. 182: 1872– 1882.
82. Lujan, A. M.,, A. J. Moyano,, I. Segura,, C. E. Argarana, and, A. M. Smania. 2007. Quorum-sensing-deficient ( lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain. Microbiology 153: 225– 237.
83. Ma, L.,, K. D. Jackson,, R. M. Landry,, M. R. Parsek, and, D. J. Wozniak. 2006. Analysis of Pseudomonas aeruginosa conditional Psl variants reveals roles for the Psl polysaccharide in adhesion and maintaining biofilm structure postattachment. J. Bacteriol. 188: 8213– 8221.
84. Mack, D.,, W. Fischer,, A. Krokotsch,, K. Leopold,, R. Hartmann,, H. Egge, and, R. Laufs. 1996. The intercellular adhesin involved in biofilm accumulation of Staphylococcus epidermidis is a linear β-1,6-linked glucosaminoglycan: purification and structural analysis. J. Bacteriol. 178: 175– 183.
85. Macnab, R. M. 1992. Genetics and biogenesis of bacterial flagella. Annu. Rev. Genet. 26: 131– 158.
86. Macnab, R. M. 1999. The bacterial flagellum: reversible rotary propellor and type III export apparatus. J. Bacteriol. 181: 7149– 7153.
87. Mah, T. C., and, G. A. O’Toole. 2001. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 9: 34– 39.
88. Mangan, E. K.,, J. Malakooti,, A. Caballero,, P. Anderson,, B. Ely, and, J. W. Gober. 1999. FlbT couples flagellum assembly to gene expression in Caulobacter crescentus. J. Bacteriol. 181: 6160– 6170.
89. McBride, M. J.,, T. F. Braun, and, J. L. Brust. 2003. Flavobacterium johnsoniae GldH is a lipoprotein that is required for gliding motility and chitin utilization. J. Bacteriol. 185: 6648– 6657.
90. McCarter, L. L. 2001. Polar flagellar motility of the Vibrionaceae. Microbiol. Mol. Biol. Rev. 65: 445– 462.
91. McCarter, L. L. 2006. Regulation of flagella. Curr. Opin. Microbiol. 9: 180– 186.
93. Merz, A. J.,, M. So, and, M. P. Sheetz. 2000. Pilus retraction powers bacterial twitching motility. Nature 407: 98– 102.
94. Mignot, T., and, J. R. Kirby. 2008. Genetic circuitry controlling motility behaviors of Myxococcus xanthus. Bioessays 30: 733– 743.
95. Molin, S., and, T. Tolker-Nielsen. 2003. Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure. Curr. Opin. Biotechnol. 14: 255– 261.
96. 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: 7335– 7343.
97. Nambu, T.,, T. Minamino,, R. M. Macnab, and, K. Kutsukake. 1999. Peptidoglycan-hydrolyzing activity of the FlgJ protein, essential for flagellar rod formation in Salmonella typhimurium. J. Bacteriol. 181: 1555– 1561.
98. Nancharaiah, Y. V.,, P. Wattiau,, S. Wuertz,, S. Bathe,, S. V. Mohan,, P. A. Wilderer, and, M. Hausner. 2003. Dual labeling of Pseudomonas putida with fluorescent proteins for in situ monitoring of conjugal transfer of the TOL plasmid. Appl. Environ. Microbiol. 69: 4846– 4852.
99. Nivens, D. E.,, D. E. Ohman,, J. Williams, and, M. J. Franklin. 2001. Role of alginate and its O acetylation in formation of Pseudomonas aeruginosa microcolonies and biofilms. J. Bacteriol. 183: 1047– 1057.
100. Ohnishi, K.,, K. Kutsukake,, H. Suzuki, and, T. Iino. 1990. Gene fliA encodes an alternative sigma factor specific for flagellar operons in Salmonella typhimurium. Mol. Gen. Genet. 221: 139– 147.
101. Ohnishi, K.,, K. Kutsukake,, H. Suzuki, and, T. Lino. 1992. A novel transcriptional regulation mechanism in the flagellar regulon of Salmonella typhimurium: an antisigma factor inhibits the activity of the flagellum-specific sigma factor, sigma F. Mol. Microbiol. 6: 3149– 3157.
102. O’Shea,, T. M.,, A. H. Klein,, K. Geszvain,, A. J. Wolfe, and, K. L. Visick. 2006. Diguanylate cyclases control magnesium-dependent motility of Vibrio fischeri. J. Bacteriol. 188: 8196– 8205.
103. O’Toole,, G.,, H. B. Kaplan, and, R. Kolter. 2000. Biofilm formation as microbial development. Annu. Rev. Microbiol. 54: 49– 79.
104. O’Toole,, G. A. 1998. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple convergent signalling pathways: a genetic analysis. Mol. Microbiol. 28: 449– 461.
105. O’Toole,, G. A., and, R. Kolter. 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 30: 295– 304.
106. Paget, M. S., and, J. D. Helmann. 2003. The sigma70 family of sigma factors. Genome Biol. 4: 203.
107. Parsek, M. R., and, P. K. Singh. 2003. Bacterial biofilms: an emerging link to disease pathogenesis. Annu. Rev. Microbiol. 57: 677– 701.
108. 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: 715– 727.
109. Pelicic, V. 2008. Type IV pili: e pluribus unum? Mol. Microbiol. 68: 827– 837.
110. 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: 2434– 2446.
111. Pratt, L. A., and, R. Kolter. 1998. Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Mol. Microbiol. 30: 285– 293.
112. Prigent-Combaret,, C.,, G. Prensier,, T. T. Le Thi,, O. Vidal,, P. Lejeune, and, C. Dorel. 2000. Developmental pathway for biofilm formation in curli-producing Escherichia coli strains: role of flagella, curli and colanic acid. Environ. Microbiol. 2: 450– 464.
113. Pruzzo, C.,, L. Vezzulli, and, R. R. Colwell. 2008. Global impact of Vibrio cholerae interactions with chitin. Environ. Microbiol. 10: 1400– 1410.
114. Purevdorj, B.,, J. W. Costerton, and, P. Stoodley. 2002. Influence of hydrodynamics and cell signaling on the structure and behavior of Pseudomonas aeruginosa biofilms. Appl. Environ. Microbiol. 68: 4457– 4464.
115. Ross, P.,, R. Mayer,, H. Weinhouse,, D. Amikam,, Y. Huggirat,, M. Benziman,, E. de Vroom,, A. Fidder,, P. de Paus, and, L. Sliedregt. 1990. The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, tri-mer, and phosphothioate derivatives. J. Biol. Chem. 265: 18933– 18943.
116. Ryjenkov, D. A.,, R. Simm,, U. Romling, 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: 30310– 30314.
117. Saini, S.,, J. D. Brown,, P. D. Aldridge, and, C. V. Rao. 2008. FliZ Is a posttranslational activator of FlhD 4C 2-dependent flagellar gene expression. J. Bacteriol. 190: 4979– 4988.
118. Samatey, F. A.,, K. Imada,, S. Nagashima,, F. Vonderviszt,, T. Kumasaka,, M. Yamamoto, and, K. Namba. 2001. Structure of the bacterial flagellar protofilament and implications for a switch for supercoiling. Nature 410: 331– 337.
119. Satoh, H.,, T. Yamakawa,, T. Kindaichi,, T. Ito, and, S. Okabe. 2006. Community structures and activities of nitrifying and denitrifying bacteria in industrial wastewater-treating biofilms. Biotechnol. Bioeng. 94: 762– 772.
120. Sauer, K.,, A. K. Camper,, G. D. Ehrlich,, J. W. Costerton, and, D. G. Davies. 2002. Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J. Bacteriol. 184: 1140– 1154.
121. Shrout, J. D.,, D. L. Chopp,, C. L. Just,, M. Hentzer,, M. Givskov, and, M. R. Parsek. 2006. The impact of quorum sensing and swarming motility on Pseudomonas aeruginosa biofilm formation is nutritionally conditional. Mol. Microbiol. 62: 1264– 1277.
122. Singh, P.,, M. R. Parsek,, E. P. Greenberg, and, M. J. Welsh. 2002. A component of innate immunity prevents bacterial biofilm development. Nature 417: 552– 555.
123. Skerker, J. M., and, H. C. Berg. 2001. Direct observation of extension and retraction of type IV pili. Proc. Natl. Acad. Sci. USA 98: 6901– 6904.
124. 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.
125. Soutourina, O. A., and, P. N. Bertin. 2003. Regulation cascade of flagellar expression in gram-negative bacteria. FEMS Microbiol. Rev. 27: 505– 523.
126. Stewart, P. S. 2003. Diffusion in biofilms. J. Bacteriol. 185: 1485– 1491.
127. Stewart, P. S., and, J. W. Costerton. 2001. Antibiotic resistance of bacteria in biofilms. Lancet 358: 135– 138.
128. Stoodley, P.,, R. Cargo,, C. J. Rupp,, S. Wilson, and, I. Klapper. 2002. Biofilm material properties as related to shear-induced deformation and detachment phenomena. J. Ind. Microbiol. Biotechnol. 29: 361– 367.
129. Stoodley, P.,, K. Sauer,, D. G. Davies, and, J. W. Costerton. 2002. Biofilms as complex differentiated communities. Annu. Rev. Microbiol. 56: 187– 209.
130. Studholme, D. J., and, M. Buck. 2000. The biology of enhancer-dependent transcriptional regulation in bacteria: insights from genome sequences. FEMS Microbiol. Lett. 186: 1– 9.
131. 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: 411– 413.
132. Teitzel, G. M., and, M. R. Parsek. 2003. Heavy metal resistance of biofilm and planktonic Pseudomonas aeruginosa. Appl. Environ. Microbiol. 69: 2313– 2320.
133. 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 oneidensis MR-1 biofilms by cyclic di-GMP. J. Bacteriol. 188: 2681– 2691.
134. 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.
135. Van Immerseel,, F.,, V. Eeckhaut,, F. Boyen,, F. Pasmans,, F. Haesebrouck, and, R. Ducatelle. 2008. Mutations influencing expression of the Salmonella enterica serovar Enteritidis pathogenicity island I key regulator hilA. Antonie Van Leeu-wenhoek 94: 455– 461.
136. Vasseur, P.,, I. Vallet-Gely,, C. Soscia,, S. Genin, and, A. Fil-loux. 2005. The pel genes of the Pseudomonas aeruginosa PAK strain are involved at early and late stages of biofilm formation. Microbiology 151: 985– 997.
137. Wadhams, G. H., and, J. P. Armitage. 2004. Making sense of it all: bacterial chemotaxis. Nat. Rev. Mol. Cell. Biol. 5: 1024– 1037.
138. Wagner, V. E., and, B. H. Iglewski. 2008. P. aeruginosa biofilms in CF infection. Clin. Rev. Allergy Immunol. 35: 124– 134.
139. Wall, D., and, D. Kaiser. 1999. Type IV pili and cell motility. Mol. Microbiol. 32: 1– 10.
140. Wang, S.,, R. T. Fleming,, E. M. Westbrook,, P. Matsumura, and, D. B. McKay. 2006. Structure of the Escherichia coli FlhDC complex, a prokaryotic heteromeric regulator of transcription. J. Mol. Biol. 355: 798– 808.
141. Watnick, P. I., and, R. Kolter. 1999. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol. Microbiol. 34: 586– 595.
142. Watnick, P. I.,, K. J. Fullner, and, R. Kolter. 1999. A role for the mannose-sensitive hemagglutinin in biofilm formation by Vibrio cholerae El Tor. J. Bacteriol. 181: 3606– 3609.
143. Whitchurch, C. B.,, R. A. Alm, and, J. S. Mattick. 1996. The alginate regulator AlgR and an associated sensor FimS are required for twitching motility in Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 93: 9839– 9843.
144. 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.
145. Wu, W.,, H. Badrane,, S. Arora,, H. V. Baker, and, S. Jin. 2004. MucA-mediated coordination of type III secretion and alginate synthesis in Pseudomonas aeruginosa. J. Bacteriol. 186: 7575– 7585.
146. Yildiz, F. H., and, G. K. Schoolnik. 1999. Vibrio cholerae 01 El Tor: identification of a gene cluster required for the rugose colony type, exopolysaccharide production, chlorine resistance, and biofilm formation. Proc. Natl. Acad. Sci. USA 96: 4028– 4033.
147. Yonekura, K.,, S. Maki,, D. G. Morgan,, D. J. DeRosier,, F. Vonderviszt,, K. Imada, and, K. Namba. 2000. The bacterial flagellar cap as the rotary promoter of flagellin self-assembly. Science 290: 2148– 2152.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V. 
 V.