Regulation by cyclic di-GMP in Myxococcus xanthus

The nucleotide-based second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes. Myxococcus xanthus undergoes major lifestyle changes in response to nutrient availability with the forma...

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1. Verfasser: Skotnicka, Dorota
Beteiligte: Søgaard-Andersen, Lotte (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Veröffentlicht: Philipps-Universität Marburg 2016
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2. Punta, M., P.C. Coggill, R.Y. Eberhardt, J. Mistry, J. Tate, C. Boursnell, N. Pang, K. Forslund, G. Ceric, J. Clements, A. Heger, L. Holm, E.L. Sonnhammer, S.R. Eddy, A. Bateman & R.D. Finn, (2012) The Pfam protein families database. Nucleic acids research 40: D290-301.

3. Berleman, J.E., J.J. Vicente, A.E. Davis, S.Y. Jiang, Y.-E. Seo & D.R. Zusman, (2011) FrzS regulates social motility in Myxococcus xanthus by controlling exopolysaccharide production. PLoS ONE 6: e23920.

4. Wu, S.S. & D. Kaiser, (1996) Markerless deletions of pil genes in Myxococcus xanthus generated by counterselection with the Bacillus subtilis sacB gene. J Bacteriol 178: 5817-5821.

5. Wolgemuth, C., E. Hoiczyk, D. Kaiser & G. Oster, (2002) How myxobacteria glide. Current biology : CB 12: 369-377.

6. Bowden, M.G. & H.B. Kaplan, (1998) The Myxococcus xanthus lipopolysaccharide O- antigen is required for social motility and multicellular development. Mol Microbiol 30: 275-284.

7. Bellini, D., D.L. Caly, Y. McCarthy, M. Bumann, S.-Q. An, J.M. Dow, R.P. Ryan & M.A. Walsh, (2014) Crystal structure of an HD-GYP domain cyclic-di-GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre. Mol Microbiol 91: 26-38.

8. Ryan, R.P., Y. McCarthy, P.A. Kiely, R. O'Connor, C.S. Farah, J.P. Armitage & J.M. Dow, (2012a) Dynamic complex formation between HD-GYP, GGDEF and PilZ domain proteins regulates motility in Xanthomonas campestris. Mol Microbiol 86: 557-567.

9. Chin, K.H., Y.C. Lee, Z.L. Tu, C.H. Chen, Y.H. Tseng, J.M. Yang, R.P. Ryan, Y. McCarthy, J.M. Dow, A.H. Wang & S.H. Chou, (2010) The cAMP receptor-like protein CLP is a novel c-di-GMP receptor linking cell-cell signaling to virulence gene expression in Xanthomonas campestris. J Mol Biol 396: 646-662.

10. Fazli, M., A. O'Connell, M. Nilsson, K. Niehaus, J.M. Dow, M. Givskov, R.P. Ryan & T. Tolker-Nielsen, (2011) The CRP/FNR family protein Bcam1349 is a c-di-GMP effector that regulates biofilm formation in the respiratory pathogen Burkholderia cenocepacia. Mol Microbiol 82: 327-341.

11. Ryan, R.P., T. Tolker-Nielsen & J.M. Dow, (2012b) When the PilZ don't work: effectors for cyclic di-GMP action in bacteria. Trends in microbiology 20: 235-242.

12. Li, W. & Z.G. He, (2012) LtmA, a novel cyclic di-GMP-responsive activator, broadly regulates the expression of lipid transport and metabolism genes in Mycobacterium smegmatis. Nucleic Acids Res. 40: 11292–11307.

13. Søgaard-Andersen, L., F.J. Slack, H. Kimsey & D. Kaiser, (1996) Intercellular C- signaling in Myxococcus xanthus involves a branched signal transduction pathway. Genes Dev. 10: 740-754.

14. Moak, P.L., W.P. Black, R.A. Wallace, Z. Li & Z.M. Yang, (2015) The Hsp70-like StkA functions between T4P and Dif signaling proteins as a negative regulator of exopolysaccharide in Myxococcus xanthus. Peerj 3.

15. Minasov, G., S. Padavattan, L. Shuvalova, J.S. Brunzelle, D.J. Miller, A. Baslé, C. Massa, F.R. Collart, T. Schirmer & W.F. Anderson, (2009) Crystal structures of YkuI and its complex with second messenger cyclic di-GMP suggest catalytic mechanism of phosphodiester bond cleavage by EAL domains. J Biol Chem 284: 13174-13184.

16. Paul, R., S. Abel, P. Wassmann, A. Beck, H. Heerklotz & U. Jenal, (2007) Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization. J Biol Chem 282: 29170-29177.

17. Paul, R., S. Weiser, N.C. Amiot, C. Chan, T. Schirmer, B. Giese & U. Jenal, (2004) Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain. Genes & development 18: 715-727.

18. Wassmann, P., C. Chan, R. Paul, A. Beck, H. Heerklotz, U. Jenal & T. Schirmer, (2007) Structure of BeF3−-modified response regulator PleD: Implications for diguanylate cyclase activation, catalysis, and feedback inhibition. Structure 15: 915-927.

19. Christen, M., B. Christen, M. Folcher, A. Schauerte & 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.

20. Aldridge, P., R. Paul, P. Goymer, P. Rainey & U. Jenal, (2003) Role of the GGDEF regulator PleD in polar development of Caulobacter crescentus. Mol Microbiol 47: 1695-1708.

21. Duerig, A., S. Abel, M. Folcher, M. Nicollier, T. Schwede, N. Amiot, B. Giese & U. Jenal, (2009) Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression. Genes & development 23: 93-104.

22. Boehm, A., M. Kaiser, H. Li, C. Spangler, C.A. Kasper, M. Ackermann, V. Kaever, V. Sourjik, V. Roth & U. Jenal, (2010) Second messenger-mediated adjustment of bacterial swimming velocity. Cell 141: 107-116.

23. Spangler, C., A. Bohm, U. Jenal, R. Seifert & V. Kaever, (2010) A liquid chromatography-coupled tandem mass spectrometry method for quantitation of cyclic di-guanosine monophosphate. Journal of microbiological methods 81: 226-231.

24. Abel, S., P. Chien, P. Wassmann, T. Schirmer, V. Kaever, M.T. Laub, T.A. Baker & U. Jenal, (2011) Regulatory cohesion of cell cycle and cell differentiation through interlinked phosphorylation and second messenger networks. Molecular cell 43: 550-560.

25. Nesper, J., A. Reinders, T. Glatter, A. Schmidt & U. Jenal, (2012) A novel capture compound for the identification and analysis of cyclic di-GMP binding proteins. Journal of proteomics 75: 4874-4878.

26. Petters, T., X. Zhang, J. Nesper, A. Treuner-Lange, N. Gomez-Santos, M. Hoppert, U. Jenal & L. Sogaard-Andersen, (2012) The orphan histidine protein kinase SgmT is a c-di-GMP receptor and regulates composition of the extracellular matrix together with the orphan DNA binding response regulator DigR in Myxococcus xanthus. Mol Microbiol 84: 147-165.

27. Bharati, B.K., I.M. Sharma, S. Kasetty, M. Kumar, R. Mukherjee & D. Chatterji, (2012) A full-length bifunctional protein involved in c-di-GMP turnover is required for long-term survival under nutrient starvation in Mycobacterium smegmatis. Microbiol-Sgm 158: 1415-1427.

28. Hobley, L., R.K. Fung, C. Lambert, M.A. Harris, J.M. Dabhi, S.S. King, S.M. Basford, K. Uchida, R. Till, R. Ahmad, S. Aizawa, M. Gomelsky & R.E. Sockett, (2012) Discrete cyclic di-GMP-dependent control of bacterial predation versus axenic growth in Bdellovibrio bacteriovorus. PLoS Pathogens 8: e1002493.

29. Lobedanz, S. & L. Sogaard-Andersen, (2003) Identification of the C-signal, a contact- dependent morphogen coordinating multiple developmental responses in Myxococcus xanthus. Genes & development 17: 2151-2161.

30. Jelsbak, L. & L. Søgaard-Andersen, (1999) The cell surface-associated intercellular C- signal induces behavioral changes in individual Myxococcus xanthus cells during fruiting body morphogenesis. Proc Natl Acad Sci USA 96: 5031-5036.

31. Duvel, J., D. Bertinetti, S. Moller, F. Schwede, M. Morr, J. Wissing, L. Radamm, B. Zimmermann, H.G. Genieser, L. Jansch, F.W. Herberg & S. Haussler, (2012) A chemical proteomics approach to identify c-di-GMP binding proteins in Pseudomonas aeruginosa. Journal of microbiological methods 88: 229-236.

32. Huang, B., C.B. Whitchurch & J.S. Mattick, (2003) FimX, a multidomain protein connecting environmental signals to twitching motility in Pseudomonas aeruginosa. J Bacteriol 185: 7068-7076.

33. Lee, V.T., J.M. Matewish, J.L. Kessler, M. Hyodo, Y. Hayakawa & S. Lory, (2007) A cyclic-di-GMP receptor required for bacterial exopolysaccharide production. Mol Microbiol 65: 1474-1484.

34. Muñoz -Dorado, J., S. Inouye & M. Inouye, (1991) A Gene Encoding a Protein Serine Threonine Kinase Is Required for Normal Development of M. xanthus, a Gram- Negative Bacterium. Cell 67: 995-1006.

35. Christen, B., M. Christen, R. Paul, F. Schmid, M. Folcher, P. Jenoe, M. Meuwly & U. Jenal, (2006) Allosteric control of cyclic di-GMP signaling. J Biol Chem 281: 32015-32024.

36. Harman, J.G., (2001) Allosteric regulation of the cAMP receptor protein. Biochim Biophys Acta 1547: 1-17.

37. Lancero, H.L., S. Castaneda, N.B. Caberoy, X. Ma, A.G. Garza & W. Shi, (2005) Analysing protein–protein interactions of the Myxococcus xanthus Dif signalling pathway using the yeast two-hybrid system. Microbiology 151: 1535-1541.

38. 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 & 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.

39. Heering, J., (2013) Analysis of the response regulator ActA and localization studies of the histidine kinase SgmT in Myxococcus xanthus. In.: BSc thesis, Philipps- Universität Marburg, pp.

40. Yang, Z.M., Y.Z. Geng, D. Xu, H.B. Kaplan & W.Y. Shi, (1998b) A new set of chemotaxis homologues is essential for Myxococcus xanthus social motility. Mol Microbiol 30: 1123-1130.

41. Rotem, O., J. Nesper, I. Borovok, R. Gorovits, M. Kolot, Z. Pasternak, I. Shin, T. Glatter, S. Pietrokovski, U. Jenal & E. Jurkevitch, (2015) An extended cyclic di- GMP network in the predatory bacterium Bdellovibrio bacteriovorus. J Bacteriol.

42. Konovalova, A., S. Lobach & L. Sogaard-Andersen, (2012) A RelA-dependent two- tiered regulated proteolysis cascade controls synthesis of a contact-dependent intercellular signal in Myxococcus xanthus. Mol Microbiol 84: 260-275.

43. Anantharaman, V. & L. Aravind, (2000) Cache -a signaling domain common to animal Ca(2+)-channel subunits and a class of prokaryotic chemotaxis receptors. Trends in biochemical sciences 25: 535-537.

44. Rao, F., Y. Yang, Y. Qi & 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.

45. Cotter, P.A. & S. Stibitz, (2007) c-di-GMP-mediated regulation of virulence and biofilm formation. Current opinion in microbiology 10: 17-23.

46. Lancero, H., N.B. Caberoy, S. Castaneda, Y.N. Li, A. Lu, D. Dutton, X.Y. Duan, H.B. Kaplan, W.Y. Shi & A.G. Garza, (2004) Characterization of a Myxococcus xanthus mutant that is defective for adventurous motility and social motility. Microbiol-Sgm 150: 4085-4093.

47. Zusman, D.R., A.E. Scott, Z. Yang & J.R. Kirby, (2007) Chemosensory pathways, motility and development in Myxococcus xanthus. Nature reviews. Microbiology 5: 862-872.

48. Jakobczak, B., D. Keilberg, K. Wuichet & L. Sogaard-Andersen, (2015) Contact-and Protein Transfer-Dependent Stimulation of Assembly of the Gliding Motility Machinery in Myxococcus xanthus. PLoS Genetics 11.

49. Ross, P., Y. Aloni, H. Weinhouse, D. Michaeli, P. Weinbergerohana, R. Mayer & M. Benziman, (1986) Control of Cellulose Synthesis in Acetobacter xylinum -a Unique Guanyl Oligonucleotide Is the Immediate Activator of the Cellulose Synthase. Carbohydrate research 149: 101-117.

50. Chirwa, N.T. & M.B. Herrington, (2003) CsgD, a regulator of curli and cellulose synthesis, also regulates serine hydroxymethyltransferase synthesis in Escherichia coli K-12. Microbiol-Sgm 149: 525-535.

51. Curriculum vitae Personal data Name: Dorota Jagoda Skotnicka Date of birth: 09.02.1988

52. Agarwal, N., G. Lamichhane, R. Gupta, S. Nolan & W.R. Bishai, (2009) Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase. Nature 460: 98-102.

53. Lee, H.J., P.T. Lang, S.M. Fortune, C.M. Sassetti & T. Alber, (2012b) Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis. Nat Struct Mol Biol 19: 811-818.

54. Weber, H., C. Pesavento, A. Possling, G. Tischendorf & R. Hengge, (2006) Cyclic-di- GMP-mediated signalling within the sigma(S) network of Escherichia coli. Mol Microbiol 62: 1014-1034.

55. Hengge, R., (2010) Cyclic-di-GMP Reaches Out into the Bacterial RNA World. Sci Signal 3.

56. Römling, U., M.Y. Galperin & M. Gomelsky, (2013) Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiology and molecular biology reviews : MMBR 77: 1-52.

57. Wireman, J.W. & M. Dworkin, (1977) Developmentally induced autolysis during fruiting body formation by Myxococcus xanthus. J Bacteriol 129: 798-802.

58. O'Connor, K.A. & D.R. Zusman, (1991b) Development in Myxococcus xanthus involves differentiation into 2 cell-types, peripheral rods and spores. J Bacteriol 173: 3318-3333.

59. Singer, M. & D. Kaiser, (1995) Ectopic production of guanosine penta-and tetraphosphate can initiate early developmental gene expression in Myxococcus xanthus. Genes & development 9: 1633-1644.

60. Mignot, T., J.W. Shaevitz, P.L. Hartzell & D.R. Zusman, (2007) Evidence that focal adhesion complexes power bacterial gliding motility. Science 315: 853-856.

61. Lu, A., K. Cho, W.P. Black, X.Y. Duan, R. Lux, Z. Yang, H.B. Kaplan, D.R. Zusman & W. Shi, (2005) Exopolysaccharide biosynthesis genes required for social motility in Myxococcus xanthus. Mol Microbiol 55: 206-220.

62. Kroos, L. & D. Kaiser, (1987) Expression of many developmentally regulated genes in Myxococcus depends on a sequence of cell interactions. Genes Dev. 1: 840- 854.

63. Konovalova, A., T. Petters & L. Sogaard-Andersen, (2010) Extracellular biology of Myxococcus xanthus. Fems Microbiol Rev 34: 89-106.

64. Bonner, P.J., W.P. Black, Z. Yang & L.J. Shimkets, (2006) FibA and PilA act cooperatively during fruiting body formation of Myxococcus xanthus. Mol Microbiol 61: 1283-1293.

65. Ogawa, M., S. Fujitani, X. Mao, S. Inouye & T. Komano, (1996) FruA, a putative transcription factor essential for the development of Myxococus xanthus. Mol Microbiol 22: 757-767.

66. Sommerfeldt, N., A. Possling, G. Becker, C. Pesavento, N. Tschowri & R. Hengge, (2009) Gene expression patterns and differential input into curli fimbriae regulation of all GGDEF/EAL domain proteins in Escherichia coli. Microbiol- Sgm 155: 1318-1331.

67. Wu, S.S. & D. Kaiser, (1995) Genetic and Functional Evidence That Type-Iv Pili Are Required for Social Gliding Motility in Myxococcus xanthus. Mol Microbiol 18: 547-558.

68. Hodgkin, J. & D. Kaiser, (1979) Genetics of gliding motility in Myxococcus xanthus (Myxobacterales): Two gene systems control movement. Mol Gen Genet 171: 177-191.

69. Curtis, P.D. & Y.V. Brun, (2010) Getting in the loop: regulation of development in Caulobacter crescentus. Microbiology and molecular biology reviews : MMBR 74: 13-41.

70. Müller, F.D., A. Treuner-Lange, J. Heider, S.M. Huntley & P.I. Higgs, (2010) Global transcriptome analysis of spore formation in Myxococcus xanthus reveals a locus necessary for cell differentiation. BMC genomics 11: 264.

71. Shimkets, L.J., (1999) Intercellular signaling during fruiting-body development of Myxococcus xanthus. Annual review of microbiology 53: 525-549.

72. Kuspa, A., L. Kroos & D. Kaiser, (1986) Intercellular signaling is required for developmental gene expression in Myxococcus xanthus. Dev. Biol. 117: 267- 276.

73. Chang, B.Y. & M. Dworkin, (1994) Isolated fibrils rescue cohesion and development in the Dsp mutant of Myxococcus xanthus. J Bacteriol. 176: 7190-7196.

74. Newell, P.D., R.D. Monds & 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: 3461-3466.

75. Fabret, C., E. Dervyn, B. Dalmais, A. Guillot, C. Marck, H. Grosjean & P. Noirot, (2011) Life without the essential bacterial tRNA Ile2-lysidine synthetase TilS: a case of tRNA gene recruitment in Bacillus subtilis. Mol Microbiol 80: 1062-1074.

76. Morgan, J.L.W., J.T. McNamara & J. Zimmer, (2014) Mechanism of activation of bacterial cellulose synthase by cyclic di-GMP. Nat Struct Mol Biol 21: 489-+.

77. Christen, M., (2007) Mechanisms of Cyclic-di-GMP Signaling. In.: Universität Basel, pp. 174.

78. Jenal, U. & J. Malone, (2006) Mechanisms of cyclic-di-GMP signaling in bacteria. Annual review of genetics 40: 385-407.

79. Thomasson, B., J. Link, A.G. Stassinopoulos, N. Burke, L. Plamann & P.L. Hartzell, (2002) MglA, a small GTPase, interacts with a tyrosine kinase to control type IV pili-mediated motility and development of Myxococcus xanthus. Mol Microbiol 46: 1399-1413.

80. Ramelot, T.A., A. Yee, J.R. Cort, A. Semesi, C.H. Arrowsmith & 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: Structure, Function, and Bioinformatics 66: 266-271.

81. Hobbs, M., E.S. Collie, P.D. Free, S.P. Livingston & J.S. Mattick, (1993) PilS and PilR, a two-component transcriptional regulatory system controlling expression of type 4 fimbriae in Pseudomonas aeruginosa. Mol Microbiol 7: 669-682.

82. Merz, A.J., M. So & M.P. Sheetz, (2000) Pilus retraction powers bacterial twitching motility. Nature 407: 98-102.

83. Amikam, D. & M.Y. Galperin, (2006) PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22: 3-6.

84. Magnusson, L.U., A. Farewell & T. Nystrom, (2005) ppGpp: a global regulator in Escherichia coli. Trends in microbiology 13: 236-242.

85. Hengge, R., (2009) Principles of c-di-GMP signalling in bacteria. Nature reviews. Microbiology 7: 263-273.

86. Curtis, P.D., J. Atwood, 3rd, R. Orlando & L.J. Shimkets, (2007) Proteins associated with the Myxococcus xanthus extracellular matrix. J Bacteriol 189: 7634-7642.

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 & M. Benziman, (1987) Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature 325: 279-281.

88. Schreiter, E.R. & C.L. Drennan, (2007) Ribbon-helix-helix transcription factors: variations on a theme. Nature reviews. Microbiology 5: 710-720.

89. Sudarsan, N., E.R. Lee, Z. Weinberg, R.H. Moy, J.N. Kim, K.H. Link & R.R. Breaker, (2008) Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321: 411-413.

90. Boyd, C.D. & G.A. O'Toole, (2012) Second messenger regulation of biofilm formation: Breakthroughs in understanding c-di-GMP effector systems. Annu Rev Cell Dev Biol 28: 439-462.

91. Tozawa, Y. & Y. Nomura, (2011) Signalling by the global regulatory molecule ppGpp in bacteria and chloroplasts of land plants. Plant biology 13: 699-709.

92. Letunic, I., T. Doerks & P. Bork, (2015) SMART: recent updates, new developments and status in 2015. Nucleic Acids Res. 43: D257-D260.

93. O'Connor, K.A. & D.R. Zusman, (1997) Starvation-independent sporulation in Myxococcus xanthus involves the pathway for beta-lactamase induction and provides a mechanism for competitive cell survival. Mol Microbiol 24: 839-850.

94. Caroff, M. & D. Karibian, (2003) Structure of bacterial lipopolysaccharides. Carbohydrate research 338: 2431-2447.

95. Hagen, D.C., A.P. Bretscher & D. Kaiser, (1978) Synergism between Morphogenetic Mutants of Myxococcus xanthus. Dev Biol 64: 284-296.

96. Tschowri, N., M.A. Schumacher, S. Schlimpert, N.B. Chinnam, K.C. Findlay, R.G. Brennan & M.J. Buttner, (2014) Tetrameric c-di-GMP Mediates Effective Transcription Factor Dimerization to Control Streptomyces Development. Cell 158: 1136-1147.

97. Gronewold, T.M. & D. Kaiser, (2001) The act operon controls the level and time of C- signal production for Myxococcus xanthus development. Mol Microbiol 40: 744- 756.

98. Ellehauge, E., M. Nørregaard-Madsen & L. Søgaard-Andersen, (1998) The FruA signal transduction protein provides a checkpoint for the temporal co-ordination of intercellular signals in Myxococcus xanthus development. Mol Microbiol. 30: 807-817.

99. Zogaj, X., M. Nimtz, M. Rohde, W. Bokranz & U. Romling, (2001) The multicellular morphotypes of Salmonella typhimurium and Escherichia coli produce cellulose as the second component of the extracellular matrix. Mol Microbiol 39: 1452- 1463.

100. Wu, S.S., J. Wu & D. Kaiser, (1997) The Myxococcus xanthus pilT locus is required for social gliding motility although pili are still produced. Mol Microbiol 23: 109-121.

101. Wu, S.S., J. Wu, Y.L. Cheng & D. Kaiser, (1998) The pilH gene encodes an ABC transporter homologue required for type IV pilus biogenesis and social gliding motility in Myxococcus xanthus. Mol Microbiol 29: 1249-1261.

102. Ryjenkov, D.A., R. Simm, U. Römling & 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.

103. Merighi, M., V.T. Lee, M. Hyodo, Y. Hayakawa & 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.

104. Lovering, A.L., M.J. Capeness, C. Lambert, L. Hobley & R.E. Sockett, (2011) The structure of an unconventional HD-GYP protein from Bdellovibrio reveals the roles of conserved residues in this class of cyclic-di-GMP phosphodiesterases. mBio 2: e00163-00111.

105. Stock, A.M., V.L. Robinson & P.N. Goudreau, (2000) Two-component signal transduction. Annual review of biochemistry 69: 183-215.

106. Wall, D. & D. Kaiser, (1999) Type IV pili and cell motility. Mol Microbiol 32: 1-10.

107. Black, W.P., Q. Xu & Z. Yang, (2006) Type IV pili function upstream of the Dif chemotaxis pathway in Myxococcus xanthus EPS regulation. Mol Microbiol 61: 447-456.

108. Sun, H., D.R. Zusman & W.Y. Shi, (2000) Type IV pilus of Myxococcus xanthus is a motility apparatus controlled by the frz chemosensory system. Current Biology 10: 1143-1146.

109. Sondermann, H., N.J. Shikuma & F.H. Yildiz, (2012) You've come a long way: c-di- GMP signaling. Current opinion in microbiology 15: 140-146.

110. Mahenthiralingam, E., T.A. Urban & J.B. Goldberg, (2005) The multifarious, multireplicon Burkholderia cepacia complex. Nature reviews. Microbiology 3: 144-156.

111. Guzzo, C.R., R.K. Salinas, M.O. Andrade & C.S. Farah, (2009) PILZ protein structure and interactions with PILB and the FIMX EAL domain: implications for control of type IV pilus biogenesis. J Mol Biol 393: 848-866.

112. Whitfield, C. & M.A. Valvano, (1993) Biosynthesis and Expression of Cell-Surface Polysaccharides in Gram-Negative Bacteria. Adv Microb Physiol 35: 135-246.

113. Bulyha, I., C. Schmidt, P. Lenz, V. Jakovljevic, A. Hone, B. Maier, M. Hoppert & L. Sogaard-Andersen, (2009) Regulation of the type IV pili molecular machine by dynamic localization of two motor proteins. Mol Microbiol 74: 691-706.

114. Martinez-Granero, F., M. Redondo-Nieto, P. Vesga, M. Martin & R. Rivilla, (2014) AmrZ is a global transcriptional regulator implicated in iron uptake and environmental adaption in P. fluorescens F113. Bmc Genomics 15.

115. He, K. & C.E. Bauer, (2014) Chemosensory signaling systems that control bacterial survival. Trends in microbiology 22: 389-398.

116. Ryjenkov, D.A., M. Tarutina, O.V. Moskvin & M. Gomelsky, (2005) Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: Insights into biochemistry of the GGDEF protein domain. J Bacteriol 187: 1792-1798.

117. Yang, Z., Y. Geng & W. Shi, (1998a) A DnaK homolog in Myxococcus xanthus is involved in social motility and fruiting body formation. J Bacteriol 180: 218-224.

118. Weimer, R.M., C. Creighton, A. Stassinopoulos, P. Youderian & P.L. Hartzell, (1998) A chaperone in the HSP70 family controls production of extracellular fibrils in Myxococcus xanthus. J Bacteriol 180: 5357-5368.

119. Kimura, Y., M. Ohtani & K. Takegawa, (2005) An adenylyl cyclase, CyaB, acts as an osmosensor in Myxococcus xanthus. J Bacteriol 187: 3593-3598.

120. Jelsbak, L. & L. Søgaard-Andersen, (2002) Pattern formation by a cell surface- associated morphogen in Myxococcus xanthus. Proc Natl Acad Sci USA 99: 2032-2037.

121. Tischler, A.D. & A. Camilli, (2004) Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. Mol Microbiol 53: 857-869.

122. Hickman, J.W., D.F. Tifrea & C.S. Harwood, (2005) A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. P Natl Acad Sci USA 102: 14422-14427.

123. Kimura, Y., Y. Mishima, H. Nakano & K. Takegawa, (2002) An adenylyl cyclase, CyaA, of Myxococcus xanthus functions in signal transduction during osmotic stress. J Bacteriol 184: 3578-3585.

124. Thormann, K.M., S. Duttler, R.M. Saville, M. Hyodo, S. Shukla, Y. Hayakawa & 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.

125. 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 & 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.

126. Overgaard, M., S. Wegener-Feldbrügge & L. Søgaard-Andersen, (2006) The orphan response regulator DigR is required for synthesis of extracellular matrix fibrils in Myxococcus xanthus. J Bacteriol 188: 4384-4394.

127. Li, Y., H. Sun, X. Ma, A. Lu, R. Lux, D. Zusman & W. Shi, (2003) Extracellular polysaccharides mediate pilus retraction during social motility of Myxococcus xanthus. Proc Natl Acad Sci USA 100: 5443-5448.

128. Julien, B., A.D. Kaiser & A. Garza, (2000) Spatial control of cell differentiation in Myxococcus xanthus. Proc Natl Acad Sci USA 97: 9098-9103.

129. Wu, S.S. & D. Kaiser, (1997) Regulation of expression of the pilA gene in Myxococcus xanthus. J Bacteriol 179: 7748-7758.

130. Christen, M., B. Christen, M.G. Allan, M. Folcher, P. Jeno, S. Grzesiek & 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.

131. Behmlander, R.M. & M. Dworkin, (1994a) Biochemical and structural analyses of the extracellular matrix fibrils of Myxococcus xanthus. J Bacteriol 176: 6295-6303.

132. Behmlander, R.M. & M. Dworkin, (1994b) Integral proteins of the extracellular matrix fibrils of Myxococcus xanthus. J Bacteriol 176: 6304-6311.

133. Dana, J.R. & L.J. Shimkets, (1993) Regulation of cohesion-dependent cell interactions in Myxococcus xanthus. J Bacteriol 175: 3636-3647.

134. Gill, R.E., M. Karlok & D. Benton, (1993) Myxococcus xanthus encodes an ATP- dependent protease which is required for developmental gene transcription and intercellular signaling. J Bacteriol 175: 4538-4544.

135. Ishimoto, K.S. & S. Lory, (1992) Identification of Pilr, Which Encodes a Transcriptional Activator of the Pseudomonas aeruginosa Pilin Gene. J Bacteriol 174: 3514- 3521.

136. Mccleary, W.R., B. Esmon & D.R. Zusman, (1991) Myxococcus xanthus Protein-C Is a Major Spore Surface Protein. J Bacteriol 173: 2141-2145.

137. O'Connor, K.A. & D.R. Zusman, (1991a) Behavior of peripheral rods and their role in the life-cycle of Myxococcus xanthus. J Bacteriol 173: 3342-3355.

138. Kuspa, A. & D. Kaiser, (1989) Genes Required for Developmental Signaling in Myxococcus xanthus -3 Asg Loci. J Bacteriol 171: 2762-2772.

139. Arnold, J.W. & L.J. Shimkets, (1988) Cell surface properties correlated with cohesion in Myxococcus xanthus. J Bacteriol 170: 5771-5777.

140. Shimkets, L.J., (1986a) Correlation of energy-dependent cell cohesion with social motility in Myxococcus xanthus. J Bacteriol 166: 837-841.

141. Shimkets, L.J., (1986b) Role of cell cohesion in Myxococcus xanthus fruiting body formation. J Bacteriol 166: 842-848.

142. Kuner, J.M. & D. Kaiser, (1982) Fruiting body morphogenesis in submerged cultures of Myxococcus xanthus. J Bacteriol 151: 458-461.

143. Shimkets, L.J. & D. Kaiser, (1982) Induction of coordinated movement of Myxococcus xanthus cells. J Bacteriol 152: 451-461.

144. Ferreira, R.B., L.C. Antunes, E.P. Greenberg & L.L. McCarter, (2008) Vibrio parahaemolyticus ScrC modulates cyclic dimeric GMP regulation of gene expression relevant to growth on surfaces. J Bacteriol 190: 851-860.

145. Shi, X., S. Wegener-Feldbrugge, S. Huntley, N. Hamann, R. Hedderich & L. Sogaard- Andersen, (2008) Bioinformatics and experimental analysis of proteins of two- component systems in Myxococcus xanthus. J Bacteriol 190: 613-624.

146. Caberoy, N.B., R.D. Welch, J.S. Jakobsen, S.C. Slater & A.G. Garza, (2003) Global mutational analysis of NtrC-like activators in Myxococcus xanthus: identifying activator mutants defective for motility and fruiting body development. J Bacteriol. 185: 6083-6094.

147. Jakovljevic, V., S. Leonardy, M. Hoppert & L. Sogaard-Andersen, (2008) PilB and PilT are ATPases acting antagonistically in type IV pilus function in Myxococcus xanthus. J Bacteriol 190: 2411-2421.

148. Kottel, R.H., K. Bacon, D. Clutter & D. White, (1975) Coats from Myxococcus xanthus: characterization and synthesis during myxospore differentiation. J Bacteriol 124: 550-557.

149. Hickman, J.W. & C.S. Harwood, (2008) Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor. Mol Microbiol 69: 376-389.

150. Clausen, M., V. Jakovljevic, L. Sogaard-Andersen & B. Maier, (2009) High-Force Generation Is a Conserved Property of Type IV Pilus Systems. J Bacteriol 191: 4633-4638.

151. Navarro, M.V., N. De, N. Bae, Q. Wang & H. Sondermann, (2009) Structural analysis of the GGDEF-EAL domain-containing c-di-GMP receptor FimX. Structure 17: 1104-1116.

152. Tamayo, R., J.T. Pratt & A. Camilli, (2007) Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annual review of microbiology 61: 131-148.

153. Pratt, J.T., R. Tamayo, A.D. Tischler & A. Camilli, (2007) PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae. J Biol Chem 282: 12860-12870.

154. Krasteva, P.V., J.C. Fong, N.J. Shikuma, S. Beyhan, M.V. Navarro, F.H. Yildiz & H. Sondermann, (2010) Vibrio cholerae VpsT regulates matrix production and motility by directly sensing cyclic di-GMP. Science 327: 866-868.

155. Ryan, R.P., Y. McCarthy, M. Andrade, C.S. Farah, J.P. Armitage & J.M. Dow, (2010) Cell-cell signal-dependent dynamic interactions between HD-GYP and GGDEF domain proteins mediate virulence in Xanthomonas campestris. Proc Natl Acad Sci USA 107: 5989-5994.

156. Nan, B.Y., E.M.F. Mauriello, I.H. Sun, A. Wong & D.R. Zusman, (2010) A multi-protein complex from Myxococcus xanthus required for bacterial gliding motility. Mol Microbiol 76: 1539-1554.

157. Paul, K., V. Nieto, W.C. Carlquist, D.F. Blair & R.M. Harshey, (2010) The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a " backstop brake " mechanism. Mol Cell 38: 128-139.

158. Black, W.P., F.D. Schubot, Z. Li & Z.M. Yang, (2010) Phosphorylation and Dephosphorylation among Dif Chemosensory Proteins Essential for Exopolysaccharide Regulation in Myxococcus xanthus. J Bacteriol 192: 4267- 4274.

159. Levi, A., M. Folcher, U. Jenal & H.A. Shuman, (2011) Cyclic diguanylate signaling proteins control intracellular growth of Legionella pneumophila. mBio 2: e00316- 00310.

160. Qi, Y., M.L.C. Chuah, X. Dong, K. Xie, Z. Luo, K. Tang & Z.-X. Liang, (2011) Binding of cyclic diguanylate in the non-catalytic EAL domain of FimX induces a long- range conformational change. J Biol Chem 286: 2910-2917.

161. Nan, B., J. Chen, J.C. Neu, R.M. Berry, G. Oster & D.R. Zusman, (2011) Myxobacteria gliding motility requires cytoskeleton rotation powered by proton motive force. Proc Natl Acad Sci USA 108: 2498-2503.

162. Shin, J.S., K.S. Ryu, J. Ko, A. Lee & B.S. Choi, (2011) Structural characterization reveals that a PilZ domain protein undergoes substantial conformational change upon binding to cyclic dimeric guanosine monophosphate. Protein Sci 20: 270- 277.

163. Bordeleau, E., L.C. Fortier, F. Malouin & V. Burrus, (2011) c-di-GMP turn-over in Clostridium difficile is controlled by a plethora of diguanylate cyclases and phosphodiesterases. PLoS Genetics 7: e1002039.

164. Habazettl, J., M.G. Allan, U. Jenal & S. Grzesiek, (2011) Solution Structure of the PilZ Domain Protein PA4608 Complex with Cyclic di-GMP Identifies Charge Clustering as Molecular Readout. J Biol Chem 286: 14304-14314.

165. Gomelsky, M., (2011) cAMP, c-di-GMP, c-di-AMP and now cGMP: bacteria use them all! Mol Microbiol 79: 562-565.

166. Sun, M., M. Wartel, E. Cascales, J.W. Shaevitz & T. Mignot, (2011) Motor-driven intracellular transport powers bacterial gliding motility. Proc Natl Acad Sci USA 108: 7559-7564.

167. Sultan, S.Z., J. E. Pitzer, T. Boquoi, G. Hobbs, M.R. Miller & M. A. Motaleb, (2011) Analysis of the HD-GYP domain cyclic dimeric GMP phosphodiesterase reveals a role in motility and the enzootic life cycle of Borrelia burgdorferi. Infect. Immun. 79: 3273-3283.

168. Giglio, K.M., N. Caberoy, G. Suen, D. Kaiser & A.G. Garza, (2011) A cascade of coregulating enhancer binding proteins initiates and propagates a multicellular developmental program. Proc Natl Acad Sci USA 108: E431–E439.

169. Harris, B.Z., D. Kaiser & M. Singer, (1998) The guanosine nucleotide (p)ppGpp initiates development and A-factor production in Myxococcus xanthus. Genes & development 12: 1022-1035.

170. Luciano, J., R. Agrebi, A.V. Le Gall, M. Wartel, F. Fiegna, A. Ducret, C. Brochier- Armanet & T. Mignot, (2011) Emergence and modular evolution of a novel motility machinery in bacteria. PLoS genetics 7: e1002268.

171. Roelofs, K.G., J.X. Wang, H.O. Sintim & V.T. Lee, (2011) Differential radial capillary action of ligand assay for high-throughput detection of protein-metabolite interactions. Proc Natl Acad Sci USA 108: 15528-15533.

172. Srivastava, D., R.C. Harris & C.M. Waters, (2011) Integration of cyclic di-GMP and quorum sensing in the control of vpsT and aphA in Vibrio cholerae. J Bacteriol 193: 6331-6341.

173. Bretl, D.J., C. Demetriadou & T.C. Zahrt, (2011) Adaptation to Environmental Stimuli within the Host: Two-Component Signal Transduction Systems of Mycobacterium tuberculosis. Microbiol Mol Biol R 75: 566-582.

174. Shikuma, N.J., J.C. Fong & F.H. Yildiz, (2012) Cellular levels and binding of c-di-GMP control subcellular localization and activity of the Vibrio cholerae transcriptional regulator VpsT. PLoS Pathogens 8: e1002719.

175. Lee, B., C. Holkenbrink, A. Treuner-Lange & P.I. Higgs, (2012a) Myxococcus xanthus developmental cell fate production: heterogeneous accumulation of developmental regulatory proteins and reexamination of the role of MazF in developmental lysis. J Bacteriol 194: 3058-3068.

176. Whitney, J.C., K.M. Colvin, L.S. Marmont, H. Robinson, M.R. Parsek & P.L. Howell, (2012) Structure of the Cytoplasmic Region of PelD, a Degenerate Diguanylate Cyclase Receptor That Regulates Exopolysaccharide Production in Pseudomonas aeruginosa. J Biol Chem 287: 23582-23593.

177. Krasteva, P.V., K.M. Giglio & H. Sondermann, (2012) Sensing the messenger: The diverse ways that bacteria signal through c-di-GMP. Protein Sci. 21: 929-948.

178. Chen, Y., Y. Chai, J.H. Guo & R. Losick, (2012) Evidence for cyclic di-GMP-mediated signaling in Bacillus subtilis. J Bacteriol 194: 5080-5090.

179. Black, W.P. & Z. Yang, (2004) Myxococcus xanthus chemotaxis homologs DifD and DifG negatively regulate fibril polysaccharide production. J Bacteriol 186: 1001- 1008.

180. Steiner, S., C. Lori, A. Boehm & U. Jenal, (2013) Allosteric activation of exopolysaccharide synthesis through cyclic di-GMP-stimulated protein-protein interaction. EMBO J 32: 354-368.

181. Shanahan, C.A. & S.A. Strobel, (2012) The bacterial second messenger c-di-GMP: probing interactions with protein and RNA binding partners using cyclic dinucleotide analogs. Organic & biomolecular chemistry 10: 9113-9129.

182. Kazmierczak, B.I., M.B. Lebron & T.S. Murray, (2006) Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa. Mol Microbiol 60: 1026-1043.

183. Vorobiev, S., H. Neely, B. Yu, J. Seetharaman, R. Xiao, T. Acton, G. Montelione & J. Hunt, (2012) Crystal structure of a catalytically active GG(D/E)EF diguanylate cyclase domain from Marinobacter aquaeolei with bound c-di-GMP product. J Struct Funct Genomics 13: 177-183.

184. Christen, M., H.D. Kulasekara, B. Christen, B.R. Kulasekara, L.R. Hoffman & S.I. Miller, (2010) Asymmetrical Distribution of the Second Messenger c-di-GMP upon Bacterial Cell Division. Science 328: 1295-1297.

185. Friedrich, C., I. Bulyha & L. Sogaard-Andersen, (2014) Outside-in assembly pathway of the type IV pilus system in Myxococcus xanthus. J Bacteriol 196: 378-390.

186. Chen, Z.H. & P. Schaap, (2012) The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium. Nature 488: 680-683.

187. Siewering, K., S. Jain, C. Friedrich, M.T. Webber-Birungi, D.A. Semchonok, I. Binzen, A. Wagner, S. Huntley, J. Kahnt, A. Klingl, E.J. Boekema, L. Sogaard-Andersen & C. van der Does, (2014) Peptidoglycan-binding protein TsaP functions in surface assembly of type IV pili. Proc Natl Acad Sci USA 111: E953-961.

188. Lombard, V., H.G. Ramulu, E. Drula, P.M. Coutinho & B. Henrissat, (2014) The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res 42: D490-D495.

189. Kaiser, D., (1979) Social gliding is correlated with the presence of pili in Myxococcus xanthus. Proc Natl Acad Sci USA 76: 5952-5956.

190. Hodgkin, J. & D. Kaiser, (1977) Cell-to-Cell Stimulation of Movement in Nonmotile Mutants of Myxococcus. Proc Natl Acad Sci USA 74: 2938-2942.

191. Cohen, D., U. Mechold, H. Nevenzal, Y. Yarmiyhu, T.E. Randall, D.C. Bay, J.D. Rich, M.R. Parsek, V. Kaever, J.J. Harrison & E. Banin, (2015) Oligoribonuclease is a central feature of cyclic diguanylate signaling in Pseudomonas aeruginosa. Proc Natl Acad Sci USA 112: 11359-11364.

192. Orr, M.W., G.P. Donaldson, G.B. Severin, J. Wang, H.O. Sintim, C.M. Waters & V.T. Lee, (2015) Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover. Proc Natl Acad Sci USA 112: E5048-5057.

193. Chan, C., R. Paul, D. Samoray, N.C. Amiot, B. Giese, U. Jenal & T. Schirmer, (2004) Structural basis of activity and allosteric control of diguanylate cyclase. Proc. Natl. Acad. Sci. USA 101: 17084-17089.

194. Yang, Z., X. Ma, L. Tong, H.B. Kaplan, L.J. Shimkets & W. Shi, (2000) Myxococcus xanthus dif genes are required for biogenesis of cell surface fibrils essential for social gliding motility. J Bacteriol 182: 5793-5798.

195. Sun, J., A. Hesketh & M. Bibb, (2001) Functional analysis of relA and rshA, two relA/spoT homologues of Streptomyces coelicolor A3(2). J Bacteriol 183: 3488- 3498.

196. Guzzo, C.R., G. Dunger, R.K. Salinas & C.S. Farah, (2013) Structure of the PilZ– FimXEAL–c-di-GMP complex responsible for the regulation of bacterial type IV pilus biogenesis. J Mol Biol 425: 2174-2197.