Publikationsserver der Universitätsbibliothek Marburg

Titel:The role of the second messenger cyclic di-GMP in Bacillus subtilis
Autor:Bedrunka, Patricia
Weitere Beteiligte: Graumann, Peter L. (Prof. Dr.)
URN: urn:nbn:de:hebis:04-z2017-05384
DDC: Chemie
Titel (trans.):Die Role des sekundären Botenstoffes zyklisches di-GMP in Bacillus subtilis


Biofilm, GGDEF Proteine, Botenstoff, cyclic di-GMP, Bacillus, zyklisches di-GMP, GGDEF proteins

The bacterial second messenger c-di-GMP represents an integral key regulator in the control of bacterial motility and biofilm formation. In this context, an increase in intracellular c-di-GMP production correlates with a sessile lifestyle, whereas low c-di-GMP levels favor planktonic cell behavior. Intracellular c-di-GMP levels are controlled by the antagonistic activity of c-di-GMP specific synthetases (diguanylate cyclases, DGCs) and hydrolases (phosphodiesterases, PDEs). Bacteria contain diverse c-di-GMP binding receptors/effectors, which exert the regulatory functions of this signaling molecule. A given bacterial genome typically encodes several paralogous copies of DGCs and PDEs. This lead to the question of how cells cope with such a multiplicity of signaling components and guarantee that specificity within certain signaling modules is mediated. Two general models for signal specificity through functional sequestration are currently discussed: the so-called local and global pool signaling hypotheses. Spatially sequestering the signal (pool) in multi-protein complexes at distinct cellular site may result in highly specific signaling pathways. Temporal and/ or conditional separation through differential expression and activation of DGCs/ PDEs/ output systems respectively, could have a distinct impact on the global c-di-GMP pool. This work investigates the role of c-di-GMP and its players in the Gram-positive model organism B. subtilis, which possesses a relatively small c-di-GMP signaling equipment. In particular, the obtained findings define a novel c-di-GMP signaling pathway regulating the production of an unknown exopolysaccharide (EPS) and furthermore imply that local and global signaling pools potentially operate in B. subtilis to regulate motility and exopolysaccharide production. The proposed c-di-GMP receptor YdaK resides in the putative EPS synthesis operon ydaJKLMN. Artificial YdaJ-N induction results in strongly altered colony biofilms, increased Congo Red staining and provokes furthermore cell clumping, which provides indirect evidence of EPS production. The putative EPS synthase components YdaM/ YdaN and YdaK co-localize to clusters predominantly at the cell poles and are statically positioned at this subcellular site, suggesting that exopolysaccharide production takes place at distinct sites of the membrane. The potential glycosyl hydrolase YdaJ is not essential for the generation of the above-described phenotypes, whereas the presence of YdaK is required, implying an involvement of the second messenger c-di-GMP. To approach the potential regulation of exopolysaccharide production through c-di-GMP via YdaK, different combinations of overexpression and deletion mutants of the operon and of dgc genes, respectively, were generated. Importantly, the presence of dgcK was shown to be indispensable for the production of the unknown EPS, thereby revealing a new function for one of the three known DGC enzymes. DgcK and YdaK partially co-localize to the same subcellular positions at the cell membrane implying close proximity of these players, which strongly suggests that YdaK receives its activation signal directly from the spatially close DgcK in agreement with the local pool hypothesis. The cytoplasmic DgcP synthetase can complement for DgcK only upon overproduction, while the third c-di-GMP synthetase, DgcW, seems not to be part of the signaling pathway. Removal of the regulatory EAL domain from DgcW reveals a distinct function in biofilm formation. Therefore, our study is compatible with the local pool signaling hypothesis, but shows that in case of the yda operon, this can easily be overcome by overproduction of non-cognate DGCs, indicating that global pools can also confer signals to this regulatory circuit. Furthermore, indications are provided within this study that all three DGCs might cooperate in inhibition of motility via the c-di-GMP receptor DgrA indicating that DgrA depends on globally elevated c-di-GMP levels.

Bibliographie / References

  1. Morgan, J.L., Strumillo, J., and Zimmer, J. (2013). Crystallographic snapshot of cellulose synthesis and membrane translocation. Nature 493(7431), 181-186. doi: 10.1038/nature11744.
  2. Civril, F., Deimling, T., de Oliveira Mann, C.C., Ablasser, A., Moldt, M., Witte, G., et al . (2013). Structural mechanism of cytosolic DNA sensing by cGAS. Nature 498(7454), 332-337. doi: 10.1038/nature12305.
  3. Beavo, J.A., and Brunton, L.L. (2002). Cyclic nucleotide research - still expanding after half a century. Nat Rev Mol Cell Biol 3(9), 710-718. doi: 10.1038/nrm911.
  4. Jenal, U., Reinders, A., and Lori, C. (2017). Cyclic di-GMP: second messenger extraordinaire. Nat Rev Microbiol. doi: 10.1038/nrmicro.2016.190.
  5. Hengge, R. (2009). Principles of c-di-GMP signalling in bacteria. Nat Rev Microbiol 7(4), 263-273. doi: 10.1038/nrmicro2109.
  6. Morgan, J.L., McNamara, J.T., and Zimmer, J. (2014). Mechanism of activation of bacterial cellulose synthase by cyclic di-GMP. Nat Struct Mol Biol 21(5), 489-496. doi: 10.1038/nsmb.2803.
  7. Liang, Z.X. (2015). The expanding roles of c-di-GMP in the biosynthesis of exopolysaccharides and secondary metabolites. Nat Prod Rep 32(5), 663-683. doi: 10.1039/c4np00086b.
  8. Kulasakara, H., Lee, V., Brencic, A., Liberati, N., Urbach, J., Miyata, S., et al. (2006). Analysis of Pseudomonas aeruginosa diguanylate cyclases and phosphodiesterases reveals a role for bis-(3'-5')-cyclic-GMP in virulence. Proc Natl Acad Sci U S A 103(8), 2839-2844. doi: 10.1073/pnas.0511090103.
  9. Christen, M., Christen, B., Allan, M.G., Folcher, M., Jeno, P., Grzesiek, S., et al . (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 U S A 104(10), 4112-4117. doi: 10.1073/pnas.0607738104.
  10. Romero, D., Aguilar, C., Losick, R., and Kolter, R. (2010). Amyloid fibers provide structural integrity to Bacillus subtilis biofilms. Proc Natl Acad Sci U S A 107(5), 2230-2234. doi: 10.1073/pnas.0910560107.
  11. Ryan, R.P., McCarthy, Y., Andrade, M., Farah, C.S., Armitage, J.P., and Dow, J.M. (2010). Cell-cell signaldependent dynamic interactions between HD-GYP and GGDEF domain proteins mediate virulence in Xanthomonas campestris. Proc Natl Acad Sci U S A 107(13), 5989-5994. doi: 10.1073/pnas.0912839107.
  12. Asally, M., Kittisopikul, M., Rue, P., Du, Y., Hu, Z., Cagatay, T., et al . (2012). Localized cell death focuses mechanical forces during 3D patterning in a biofilm. Proc Natl Acad Sci U S A 109(46), 18891-18896. doi: 10.1073/pnas.1212429109.
  13. Hobley, L., Ostrowski, A., Rao, F.V., Bromley, K.M., Porter, M., Prescott, A.R., et al . (2013). BslA is a selfassembling bacterial hydrophobin that coats the Bacillus subtilis biofilm. Proc Natl Acad Sci U S A 110(33), 13600-13605. doi: 10.1073/pnas.1306390110.
  14. Nelson, J.W., Sudarsan, N., Phillips, G.E., Stav, S., Lunse, C.E., McCown, P.J., et al. (2015). Control of bacterial exoelectrogenesis by c-AMP-GMP. Proc Natl Acad Sci U S A 112(17), 5389-5394. doi: 10.1073/pnas.1419264112.
  15. Orr, M.W., Donaldson, G.P., Severin, G.B., Wang, J., Sintim, H.O., Waters, C.M., et al . (2015). Oligoribonuclease is the primary degradative enzyme for pGpG in Pseudomonas aeruginosa that is required for cyclic-di-GMP turnover. Proc Natl Acad Sci U S A 112(36), E5048-5057. doi: 10.1073/pnas.1507245112.
  16. Branda, S.S., Gonzalez-Pastor, J.E., Ben-Yehuda, S., Losick, R., and Kolter, R. (2001). Fruiting body formation by Bacillus subtilis. Proc Natl Acad Sci U S A 98(20), 11621-11626. doi: 10.1073/pnas.191384198.
  17. Roux, D., Cywes-Bentley, C., Zhang, Y.F., Pons, S., Konkol, M., Kearns, D.B., et al. (2015). Identification of Poly-N-acetylglucosamine as a Major Polysaccharide Component of the Bacillus subtilis Biofilm Matrix. J Biol Chem 290(31), 19261-19272. doi: 10.1074/jbc.M115.648709.
  18. Christen, B., Christen, M., Paul, R., Schmid, F., Folcher, M., Jenoe, P., et al . (2006). Allosteric control of cyclic di-GMP signaling. J Biol Chem 281(42), 32015-32024. doi: 10.1074/jbc.M603589200.
  19. Pratt, J.T., Tamayo, R., Tischler, A.D., and Camilli, A. (2007). PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae. J Biol Chem 282(17), 12860-12870. doi: 10.1074/jbc.M611593200.
  20. Minasov, G., Padavattan, S., Shuvalova, L., Brunzelle, J.S., Miller, D.J., Basle, A., et al . (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(19), 13174-13184. doi: 10.1074/jbc.M808221200.
  21. Amikam, D., and Galperin, M.Y. (2006). PilZ domain is part of the bacterial c-di-GMP binding protein. Bioinformatics 22(1), 3-6. doi: 10.1093/bioinformatics/bti739.
  22. Branda, S.S., Chu, F., Kearns, D.B., Losick, R., and Kolter, R. (2006). A major protein component of the Bacillus subtilis biofilm matrix. Mol Microbiol 59(4), 1229-1238. doi: 10.1111/j.1365-2958.2005.05020.x.
  23. Lee, V.T., Matewish, J.M., Kessler, J.L., Hyodo, M., Hayakawa, Y., and Lory, S. (2007). A cyclic-di-GMP receptor required for bacterial exopolysaccharide production. Mol Microbiol 65(6), 1474-1484. doi: 10.1111/j.1365-2958.2007.05879.x.
  24. Luo, Y., and Helmann, J.D. (2012). Analysis of the role of Bacillus subtilis sigma(M) in beta-lactam resistance reveals an essential role for c-di-AMP in peptidoglycan homeostasis. Mol Microbiol 83(3), 623-639. doi: 10.1111/j.1365-2958.2011.07953.x.
  25. Cairns, L.S., Hobley, L., and Stanley-Wall, N.R. (2014). Biofilm formation by Bacillus subtilis: new insights into regulatory strategies and assembly mechanisms. Mol Microbiol 93(4), 587-598. doi: 10.1111/mmi.12697.
  26. Koseoglu, V.K., Heiss, C., Azadi, P., Topchiy, E., Guvener, Z.T., Lehmann, T.E., et al. (2015). Listeria monocytogenes exopolysaccharide: origin, structure, biosynthetic machinery and c-di-GMP-dependent regulation. Mol Microbiol 96(4), 728-743. doi: 10.1111/mmi.12966.
  27. Nicolas, P., Mader, U., Dervyn, E., Rochat, T., Leduc, A., Pigeonneau, N., et al. (2012). Conditiondependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science 335(6072), 1103- 1106. doi: 10.1126/science.1206848.
  28. Konkol, M.A., Blair, K.M., and Kearns, D.B. (2013). Plasmid-encoded ComI inhibits competence in the ancestral 3610 strain of Bacillus subtilis. J Bacteriol 195(18), 4085-4093. doi: 10.1128/jb.00696-13.
  29. Serra, D.O., Richter, A.M., and Hengge, R. (2013). Cellulose as an architectural element in spatially structured Escherichia coli biofilms. J Bacteriol 195(24), 5540-5554. doi: 10.1128/Jb.00946-13.
  30. Chen, Y., Chai, Y., Guo, J.H., and Losick, R. (2012). Evidence for cyclic Di-GMP-mediated signaling in Bacillus subtilis. J Bacteriol 194(18), 5080-5090. doi: 10.1128/JB.01092-12.
  31. Li, Y., Heine, S., Entian, M., Sauer, K., and Frankenberg-Dinkel, N. (2013). NO-induced biofilm dispersion in Pseudomonas aeruginosa is mediated by an MHYT domain-coupled phosphodiesterase. J Bacteriol 195(16), 3531-3542. doi: 10.1128/JB.01156-12.
  32. McLoon, A.L., Guttenplan, S.B., Kearns, D.B., Kolter, R., and Losick, R. (2011). Tracing the domestication of a biofilm-forming bacterium. J Bacteriol 193(8), 2027-2034. doi: 10.1128/jb.01542-10.
  33. Merritt, J.H., Ha, D.G., Cowles, K.N., Lu, W., Morales, D.K., Rabinowitz, J., et al . (2010). Specific control of Pseudomonas aeruginosa surface-associated behaviors by two c-di-GMP diguanylate cyclases. MBio 1(4). doi: 10.1128/mBio.00183-10.
  34. Dahlstrom, K.M., Giglio, K.M., Collins, A.J., Sondermann, H., and O'Toole, G.A. (2015). Contribution of physical interactions to signaling specificity between a diguanylate cyclase and its Effector. MBio 6(6), e01978-01915. doi: 10.1128/mBio.01978-15.
  35. Romling, U., Galperin, M.Y., and Gomelsky, M. (2013). Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev 77(1), 1-52. doi: 10.1128/MMBR.00043-12.
  36. Costerton, J.W., Lewandowski, Z., Caldwell, D.E., Korber, D.R., and Lappin-Scott, H.M. (1995). Microbial biofilms. Annu Rev Microbiol 49, 711-745. doi: 10.1146/annurev.mi.49.100195.003431.
  37. Zafra, O., Lamprecht-Grandio, M., de Figueras, C.G., and Gonzalez-Pastor, J.E. (2012). Extracellular DNA release by undomesticated Bacillus subtilis is regulated by early competence. PLoS One 7(11), e48716. doi: 10.1371/journal.pone.0048716.
  38. Dogsa, I., Brloznik, M., Stopar, D., and Mandic-Mulec, I. (2013). Exopolymer diversity and the role of levan in Bacillus subtilis biofilms. PLoS One 8(4), e62044. doi: 10.1371/journal.pone.0062044.
  39. Chen, L.H., Koseoglu, V.K., Guvener, Z.T., Myers-Morales, T., Reed, J.M., D'Orazio, S.E., et al . (2014). Cyclic di-GMP-dependent signaling pathways in the pathogenic Firmicute Listeria monocytogenes. PLoS Pathog 10(8), e1004301. doi: 10.1371/journal.ppat.1004301.
  40. Schmid, J., Sieber, V., and Rehm, B. (2015). Bacterial exopolysaccharides: biosynthesis pathways and engineering strategies. Front Microbiol 6, 496. doi: 10.3389/fmicb.2015.00496.
  41. Kaufmann, S.H., and Schaible, U.E. (2005). 100th anniversary of Robert Koch's Nobel Prize for the discovery of the tubercle bacillus. Trends in microbiology 13(10), 469-475.
  42. Shemesh, M., and Chai, Y. (2013). A combination of glycerol and manganese promotes biofilm formation in Bacillus subtilis via histidine kinase KinD signaling. Journal of bacteriology 195(12), 2747-2754.
  43. Eymann, C., Dreisbach, A., Albrecht, D., Bernhardt, J., Becher, D., Gentner, S., et al. (2004). A comprehensive proteome map of growing Bacillus subtilis cells. Proteomics 4(10), 2849-2876.
  44. Ozaki, S., Schalch‐ Moser, A., Zumthor, L., Manfredi, P., Ebbensgaard, A., Schirmer, T., et al. (2014). Activation and polar sequestration of PopA, ac‐ di‐ GMP effector protein involved in Caulobacter crescentus cell cycle control. Molecular microbiology 94(3), 580-594.
  45. Moradali, M.F., Ghods, S., and Rehm, B.H. (2017). Activation Mechanism and Cellular Localization of Membrane-Anchored Alginate Polymerase in Pseudomonas aeruginosa. Applied and Environmental Microbiology 83(9), e03499-03416.
  46. Paul, R., Abel, S., Wassmann, P., Beck, A., Heerklotz, H., and Jenal, U. (2007). Activation of the diguanylate cyclase PleD by phosphorylation-mediated dimerization. Journal of biological chemistry 282(40), 29170-29177.
  47. Xu, L., Venkataramani, P., Ding, Y., Liu, Y., Deng, Y., Yong, G.L., et al. (2016). A cyclic di-GMP-binding adaptor protein interacts with histidine kinase to regulate two-component signaling. Journal of Biological Chemistry 291(31), 16112-16123.
  48. Makman, R.S., and Sutherland, E.W. (1965). Adenosine 3', 5'-phosphate in Escherichia coli. Journal of Biological Chemistry 240(3), 1309-1314.
  49. Cooper, D.M., and Tabbasum, V.G. (2014). Adenylate cyclase-centred microdomains. Biochemical Journal 462(2), 199-213.
  50. Barzu, O., and Danchin, A. (1994). Adenylyl cyclases: a heterogeneous class of ATP-utilizing enzymes. Prog Nucleic Acid Res Mol Biol 49, 241-283.
  51. Berne, C., Ducret, A., Hardy, G.G., and Brun, Y.V. (2015). Adhesins involved in attachment to abiotic surfaces by Gram-negative bacteria. Microbiology spectrum 3(4).
  52. Moradali, M.F., Donati, I., Sims, I.M., Ghods, S., and Rehm, B.H. (2015). Alginate polymerization and modification are linked in Pseudomonas aeruginosa. MBio 6(3), e00453-00415.
  53. Cairns, L.S., Marlow, V.L., Bissett, E., Ostrowski, A., and Stanley‐ Wall, N.R. (2013). A mechanical signal transmitted by the flagellum controls signalling in Bacillus subtilis. Molecular microbiology 90(1), 6-21.
  54. Youngman, P., Perkins, J.B., and Losick, R. (1984). A novel method for the rapid cloning in Escherichia coli of Bacillus subtilis chromosomal DNA adjacent to Tn917 insertions. Mol Gen Genet 195(3), 424-433.
  55. Chu, F., Kearns, D.B., McLoon, A., Chai, Y., Kolter, R., and Losick, R. (2008). A novel regulatory protein governing biofilm formation in Bacillus subtilis. Molecular microbiology 68(5), 1117-1127.
  56. Høiby, N., Bjarnsholt, T., Givskov, M., Molin, S., and Ciofu, O. (2010). Antibiotic resistance of bacterial biofilms. International journal of antimicrobial agents 35(4), 322-332.
  57. Dobell (1960). Antony van Leeuwenhoek and his 'Little animals'. Dover Publications, New York, NY.
  58. Høiby, N. (2014). A personal history of research on microbial biofilms and biofilm infections. Pathogens and disease 70(3), 205-211.
  59. Murray, E.J., Kiley, T.B., and Stanley-Wall, N.R. (2009). A pivotal role for the response regulator DegU in controlling multicellular behaviour. Microbiology 155(1), 1-8.
  60. Anantharaman, V., and Aravind, L. (2003). Application of comparative genomics in the identification and analysis of novel families of membrane-associated receptors in bacteria. BMC Genomics 4(1), 34. doi: 10.1186/1471- 2164-4-34.
  61. Artsimovitch, I. (2010). A processive riboantiterminator seeks a switch to make biofilms. Molecular microbiology 76(3), 535-539.
  62. Dubey, G.P., Mohan, G.B.M., Dubrovsky, A., Amen, T., Tsipshtein, S., Rouvinski, A., et al . (2016). Architecture and characteristics of bacterial nanotubes. Developmental cell 36(4), 453-461.
  63. Irnov, I., and Winkler, W.C. (2010). A regulatory RNA required for antitermination of biofilm and capsular polysaccharide operons in Bacillales. Molecular microbiology 76(3), 559-575.
  64. Dennis, P.G., Miller, A.J., and Hirsch, P.R. (2010). Are root exudates more important than other sources of rhizodeposits in structuring rhizosphere bacterial communities? FEMS microbiology ecology 72(3), 313-327.
  65. Perego, M., Glaser, P., and Hoch, J.A. (1996). Aspartyl‐ phosphate phosphatases deactivate the response regulator components of the sporulation signal transduction system in Bacillus subtilis. Molecular microbiology 19(6), 1151-1157.
  66. Ambrose, E. (1956). A surface contact microscope for the study of cell movements. Nature 178, 1194.
  67. Arora, S.K., Ritchings, B.W., Almira, E.C., Lory, S., and Ramphal, R. (1997). A transcriptional activator, FleQ, regulates mucin adhesion and flagellar gene expression in Pseudomonas aeruginosa in a cascade manner. Journal of bacteriology 179(17), 5574-5581.
  68. Allard-Massicotte, R., Tessier, L., Lécuyer, F., Lakshmanan, V., Lucier, J.-F., Garneau, D., et al . (2016). Bacillus subtilis early colonization of Arabidopsis thaliana roots involves multiple chemotaxis receptors. mBio 7(6), e01664-01616.
  69. Remminghorst, U., and Rehm, B.H. (2006). Bacterial alginates: from biosynthesis to applications. Biotechnology letters 28(21), 1701-1712.
  70. Costerton, J.W., Cheng, K., Geesey, G.G., Ladd, T.I., Nickel, J.C., Dasgupta, M., et al . (1987). Bacterial biofilms in nature and disease. Annual Reviews in Microbiology 41(1), 435-464.
  71. Römling, U., and Galperin, M.Y. (2015). Bacterial cellulose biosynthesis: diversity of operons, subunits, products, and functions. Trends in microbiology 23(9), 545-557.
  72. Dietrich, L.E., Okegbe, C., Price-Whelan, A., Sakhtah, H., Hunter, R.C., and Newman, D.K. (2013). Bacterial community morphogenesis is intimately linked to the intracellular redox state. Journal of bacteriology 195(7), 1371-1380.
  73. Kovács, Á.T. (2016). Bacterial differentiation via gradual activation of global regulators. Current genetics 62(1), 125- 128.
  74. Nwodo, U.U., Green, E., and Okoh, A.I. (2012). Bacterial exopolysaccharides: functionality and prospects. International journal of molecular sciences 13(11), 14002-14015.
  75. Limoli, D.H., Jones, C.J., and Wozniak, D.J. (2015). Bacterial extracellular polysaccharides in biofilm formation and function. Microbiology spectrum 3(3).
  76. Morikawa, M. (2006). Beneficial biofilm formation by industrial bacteria Bacillus subtilis and related species. Journal of bioscience and bioengineering 101(1), 1-8.
  77. Hiltner, L.t. (1904). Über neuere Erfahrungen und Probleme auf dem Gebiete der Bodenbakteriologie unter besonderer Berücksichtigung der Gründüngung und Brache. Arbeiten der Deutschen Landwirtschaftlichen Gesellschaft 98, 59-78.
  78. Lemon, K., Earl, A., Vlamakis, H., Aguilar, C., and Kolter, R. (2008). Biofilm development with an emphasis on Bacillus subtilis, in Bacterial Biofilms. Springer, 1-16.
  79. Kaplan, J.á. (2010). Biofilm dispersal: mechanisms, clinical implications, and potential therapeutic uses. Journal of dental research 89(3), 205-218.
  80. Sauer, K., Rickard, A.H., and Davies, D.G. (2007). Biofilms and biocomplexity. Microbe-American Society for Microbiology 2(7), 347.
  81. Stoodley, P., Sauer, K., Davies, D., and Costerton, J.W. (2002). Biofilms as complex differentiated communities. Annual Reviews in Microbiology 56(1), 187-209.
  82. Branda, S.S., Vik, Å., Friedman, L., and Kolter, R. (2005). Biofilms: the matrix revisited. Trends in microbiology 13(1), 20-26.
  83. Kobayashi, K., and Iwano, M. (2012). BslA (YuaB) forms a hydrophobic layer on the surface of Bacillus subtilis biofilms. Molecular microbiology 85(1), 51-66.
  84. Richter, A. (2016). c-di-GMP-abhängige Signal-transduktion bei der Kontrolle der Cellulose-Synthese in Escherichia coli Biofilmen. PhD thesis. Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät.
  85. Schirmer, T. (2016). C-di-GMP Synthesis: Structural Aspects of Evolution, Catalysis and Regulation. Journal of molecular biology 428(19), 3683-3701.
  86. Axelrod, D. (1981). Cell-substrate contacts illuminated by total internal reflection fluorescence. The Journal of cell biology 89(1), 141-145.
  87. Ross, P., Mayer, R., and Benziman, M. (1991). Cellulose biosynthesis and function in bacteria. Microbiol Rev 55(1), 35-58.
  88. Becker, A. (2015) Challenges and perspectives in combinatorial assembly of novel exopoly saccharide biosynthesis pathways. Front Microbiol 6: 687.
  89. Baker, P., Whitfield, G.B., Hill, P.J., Little, D.J., Pestrak, M.J., Robinson, H., et al . (2015). Characterization of the Pseudomonas aeruginosa glycoside hydrolase PslG reveals that its levels are critical for Psl polysaccharide biosynthesis and biofilm formation. Journal of Biological Chemistry 290(47), 28374-28387.
  90. Seshasayee, A.S., Fraser, G.M., and Luscombe, N.M. (2010). Comparative genomics of cyclic-di-GMP signalling in bacteria: post-translational regulation and catalytic activity. Nucleic acids research 38(18), 5970- 5981.
  91. Schroeder, J.W., and Simmons, L.A. (2013). Complete genome sequence of Bacillus subtilis strain PY79. Genome announcements 1(6), e01085-01013.
  92. Davies, B.W., Bogard, R.W., Young, T.S., and Mekalanos, J.J. (2012). Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence. Cell 149(2), 358-370.
  93. Bellini, D., Caly, D.L., McCarthy, Y., Bumann, M., An, S.Q., Dow, J.M., et al . (2014). Crystal structure of an HD‐ GYP domain cyclic‐ di‐ GMP phosphodiesterase reveals an enzyme with a novel trinuclear catalytic iron centre. Molecular microbiology 91(1), 26-38.
  94. Corrigan, R.M., and Gründling, A. (2013). Cyclic di-AMP: another second messenger enters the fray. Nature Reviews Microbiology 11(8), 513-524.
  95. Lori, C., Ozaki, S., Steiner, S., Böhm, R., Abel, S., Dubey, B.N., et al . (2015). Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. Nature 523(7559), 236-239.
  96. Hull, T.D., Ryu, M.-H., Sullivan, M.J., Johnson, R.C., Klena, N.T., Geiger, R.M., et al . (2012). Cyclic DiGMP phosphodiesterases RmdA and RmdB are involved in regulating colony morphology and development in Streptomyces coelicolor. Journal of bacteriology 194(17), 4642-4651.
  97. Bordeleau, E., Purcell, E.B., Lafontaine, D.A., Fortier, L.-C., Tamayo, R., and Burrus, V. (2015). Cyclic diGMP riboswitch-regulated type IV pili contribute to aggregation of Clostridium difficile. Journal of bacteriology 197(5), 819-832.
  98. Richter, A.M., Povolotsky, T.L., Wieler, L.H., and Hengge, R. (2014). Cyclic‐ di‐ GMP signalling and biofilmrelated properties of the Shiga toxin‐ producing 2011 German outbreak Escherichia coli O104: H4. EMBO molecular medicine, e201404309.
  99. Baraquet, C., and Harwood, C.S. (2013). Cyclic diguanosine monophosphate represses bacterial flagella synthesis by interacting with the Walker A motif of the enhancer-binding protein FleQ. Proceedings of the National Academy of Sciences 110(46), 18478-18483.
  100. Amikam, D., and Benziman, M. (1989). Cyclic diguanylic acid and cellulose synthesis in Agrobacterium tumefaciens. J Bacteriol 171(12), 6649-6655.
  101. Biswas, K.H., Badireddy, S., Rajendran, A., Anand, G.S., and Visweswariah, S.S. (2015). Cyclic nucleotide binding and structural changes in the isolated GAF domain of Anabaena adenylyl cyclase, CyaB2. PeerJ 3, e882.
  102. Lee, M.J., Geller, A.M., Bamford, N.C., Liu, H., Gravelat, F.N., Snarr, B.D., et al . (2016). Deacetylation of fungal exopolysaccharide mediates adhesion and biofilm formation. MBio 7(2), e00252-00216.
  103. Ohlsen, K.L., Grimsley, J.K., and Hoch, J.A. (1994). Deactivation of the sporulation transcription factor Spo0A by the Spo0E protein phosphatase. Proceedings of the National Academy of Sciences 91(5), 1756-1760.
  104. Stanley, N.R., and Lazazzera, B.A. (2005). Defining the genetic differences between wild and domestic strains of Bacillus subtilis that affect poly‐ γ‐ DL‐ glutamic acid production and biofilm formation. Molecular microbiology 57(4), 1143-1158.
  105. De, N., Navarro, M.V., Raghavan, R.V., and Sondermann, H. (2009). Determinants for the activation and autoinhibition of the diguanylate cyclase response regulator WspR. Journal of molecular biology 393(3), 619-633.
  106. Lowe, P., Hodgson, J., and Perham, R. (1983). Dual role of a single multienzyme complex in the oxidative decarboxylation of pyruvate and branched-chain 2-oxo acids in Bacillus subtilis. Biochemical Journal 215(1), 133-140.
  107. Mamou, G., Mohan, G.B.M., Rouvinski, A., Rosenberg, A., and Ben-Yehuda, S. (2016). Early developmental program shapes colony morphology in bacteria. Cell reports 14(8), 1850-1857.
  108. Anantharaman, V., Aravind, L., and Koonin, E.V. (2003). Emergence of diverse biochemical activities in evolutionarily conserved structural scaffolds of proteins. Curr Opin Chem Biol 7(1), 12-20.
  109. Schmidt, A., Hammerbacher, A.S., Bastian, M., Nieken, K.J., Klockgether, J., Merighi, M., et a l . (2016). Oxygen‐ dependent regulation of c‐ di‐ GMP synthesis by SadC controls alginate production in Pseudomonas aeruginosa. Environmental microbiology.
  110. Marvasi, M., Visscher, P.T., and Casillas Martinez, L. (2010). Exopolymeric substances (EPS) from Bacillus subtilis: polymers and genes encoding their synthesis. FEMS Microbiol Lett 313(1), 1-9. doi: 10.1111/j.1574- 6968.2010.02085.x.
  111. Pérez-Mendoza, D., and Sanjuán, J. (2016). Exploiting the commons: cyclic diguanylate regulation of bacterial exopolysaccharide production. Current opinion in microbiology 30, 36-43.
  112. Reinders, A., Hee, C.-S., Ozaki, S., Mazur, A., Boehm, A., Schirmer, T., et al . (2016). Expression and genetic activation of cyclic di-GMP-specific phosphodiesterases in Escherichia coli. Journal of bacteriology 198(3), 448- 462.
  113. Rall, T.W., and Sutherland, E.W. (1958). Formation of a cyclic adenine ribonucleotide by tissue particles. J Biol Chem 232(2), 1065-1076.
  114. Romero, D., and Kolter, R. (2014). Functional amyloids in bacteria. International Microbiology 17(2), 65-73.
  115. Pokrovskaya, V., Poloczek, J., Little, D.J., Griffiths, H., Howell, P.L., and Nitz, M. (2013). Functional characterization of Staphylococcus epidermidis IcaB, a de-N-acetylase important for biofilm formation. Biochemistry 52(32), 5463-5471.
  116. Hirabayashi, K., Yuda, E., Tanaka, N., Katayama, S., Iwasaki, K., Matsumoto, T., et al . (2015). Functional dynamics revealed by the structure of the SufBCD complex, a novel ATP-binding cassette (ABC) protein that serves as a scaffold for iron-sulfur cluster biogenesis. Journal of Biological Chemistry 290(50), 29717-29731.
  117. Sommerfeldt, N., Possling, A., Becker, G., Pesavento, C., Tschowri, N., and Hengge, R. (2009). Gene expression patterns and differential input into curli fimbriae regulation of all GGDEF/EAL domain proteins in Escherichia coli. Microbiology 155(4), 1318-1331.
  118. Branda, S.S., González-Pastor, J.E., Dervyn, E., Ehrlich, S.D., Losick, R., and Kolter, R. (2004). Genes involved in formation of structured multicellular communities by Bacillus subtilis. Journal of bacteriology 186(12), 3970-3979.
  119. Solano, C., García, B., Valle, J., Berasain, C., Ghigo, J.M., Gamazo, C., et al . (2002). Genetic analysis of Salmonella enteritidis biofilm formation: critical role of cellulose. Molecular microbiology 43(3), 793-808.
  120. Wolska, K.I., Grudniak, A.M., Rudnicka, Z., and Markowska, K. (2016). Genetic control of bacterial biofilms. Journal of applied genetics 57(2), 225-238.
  121. Ausmees, N., Mayer, R., Weinhouse, H., Volman, G., Amikam, D., Benziman, M., et al . (2001). Genetic data indicate that proteins containing the GGDEF domain possess diguanylate cyclase activity. FEMS Microbiology Letters 204(1), 163-167.
  122. Lewis, P.J., and Marston, A.L. (1999). GFP vectors for controlled expression and dual labelling of protein fusions in Bacillus subtilis. Gene 227(1), 101-110.
  123. Simm, R., Morr, M., Kader, A., Nimtz, M., and Römling, U. (2004). GGDEF and EAL domains inversely regulate cyclic di‐ GMP levels and transition from sessility to motility. Molecular microbiology 53(4), 1123-1134.
  124. Kobayashi, K. (2007). Gradual activation of the response regulator DegU controls serial expression of genes for flagellum formation and biofilm formation in Bacillus subtilis. Molecular microbiology 66(2), 395-409.
  125. Inoue, H., Nojima, H., and Okayama, H. (1990). High efficiency transformation of Escherichia coli with plasmids. Gene 96(1), 23-28.
  126. Marczak, M., Dźwierzyńska, M., and Skorupska, A. (2013). Homo-and heterotypic interactions between Pss proteins involved in the exopolysaccharide transport system in Rhizobium leguminosarum bv. trifolii. Biological chemistry 394(4), 541-559.
  127. Christen, M., Christen, B., Folcher, M., Schauerte, A., and Jenal, U. (2005). Identification and characterization of a cyclic di-GMP-specific phosphodiesterase and its allosteric control by GTP. Journal of Biological Chemistry 280(35), 30829-30837.
  128. Charbonneau, H., Prusti, R.K., LeTrong, H., Sonnenburg, W.K., Mullaney, P.J., Walsh, K.A., et al . (1990). Identification of a noncatalytic cGMP-binding domain conserved in both the cGMP-stimulated and photoreceptor cyclic nucleotide phosphodiesterases. Proceedings of the National Academy of Sciences 87(1), 288- 292.
  129. Petersohn, A., Bernhardt, J., Gerth, U., Höper, D., Koburger, T., Völker, U., et al . (1999). Identification of σB-dependent genes in Bacillus subtilis using a promoter consensus-directed search and oligonucleotide hybridization. Journal of bacteriology 181(18), 5718-5724.
  130. Hickman, J.W., and Harwood, C.S. (2008). Identification of FleQ from Pseudomonas aeruginosa as ac‐ di‐ GMPresponsive transcription factor. Molecular microbiology 69(2), 376-389.
  131. Reichhardt, C., McCrate, O.A., Zhou, X., Lee, J., Thongsomboon, W., and Cegelski, L. (2016). Influence of the amyloid dye Congo red on curli, cellulose, and the extracellular matrix in E. coli during growth and matrix purification. Analytical and bioanalytical chemistry 408(27), 7709-7717.
  132. Burbulys, D., Trach, K.A., and Hoch, J.A. (1991). Initiation of sporulation in B. subtilis is controlled by a multicomponent phosphorelay. Cell 64(3), 545-552.
  133. Anderson, G., and O'toole, G. (2008). Innate and induced resistance mechanisms of bacterial biofilms, in Bacterial biofilms. Springer, 85-105.
  134. Chandrangsu, P., and Helmann, J.D. (2016). Intracellular Zn (II) Intoxication Leads to Dysregulation of the PerR Regulon Resulting in Heme Toxicity in Bacillus subtilis. PLoS genetics 12(12), e1006515.
  135. Méndez-Lorenzo, L., Porras-Domínguez, J.R., Raga-Carbajal, E., Olvera, C., Rodríguez-Alegría, M.E., Carrillo-Nava, E., et al . (2015). Intrinsic levanase activity of Bacillus subtilis 168 levansucrase (SacB). PloS one 10(11), e0143394.
  136. Banin, E., Vasil, M.L., and Greenberg, E.P. (2005). Iron and Pseudomonas aeruginosa biofilm formation. Proceedings of the National Academy of Sciences of the United States of America 102(31), 11076-11081.
  137. Chai, L., Romero, D., Kayatekin, C., Akabayov, B., Vlamakis, H., Losick, R., et al . (2013). Isolation, characterization, and aggregation of a structured bacterial matrix precursor. Journal of Biological Chemistry 288(24), 17559-17568.
  138. Ashman, D.F., Lipton, R., Melicow, M.M., and Price, T.D. (1963). Isolation of adenosine 3', 5'-monophosphate and guanosine 3', 5'-monophosphate from rat urine. Biochem Biophys Res Commun 11, 330-334.
  139. Patrick, J.E., and Kearns, D.B. (2009). Laboratory strains of Bacillus subtilis do not exhibit swarming motility. Journal of bacteriology 191(22), 7129-7133.
  140. Newell, P.D., Monds, R.D., and O'Toole, G.A. (2009). LapD is a bis-(3′, 5′)-cyclic dimeric GMP-binding protein that regulates surface attachment by Pseudomonas fluorescens Pf0-1. Proceedings of the National Academy of Sciences 106(9), 3461-3466.
  141. Matsuyama, B.Y., Krasteva, P.V., Baraquet, C., Harwood, C.S., Sondermann, H., and Navarro, M.V. (2016). Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences 113(2), E209-E218.
  142. Norman, T.M., Lord, N.D., Paulsson, J., and Losick, R. (2013). Memory and modularity in cell-fate decision making. Nature 503(7477), 481-486.
  143. Davey, M.E., and O'toole, G.A. (2000). Microbial biofilms: from ecology to molecular genetics. Microbiology and molecular biology reviews 64(4), 847-867.
  144. Shimotsu, H., and Henner, D.J. (1986). Modulation of Bacillus subtilis levansucrase gene expression by sucrose and regulation of the steady-state mRNA level by sacU and sacQ genes. Journal of bacteriology 168(1), 380-388.
  145. Anwar, N., Rouf, S.F., Römling, U., and Rhen, M. (2014). Modulation of biofilm-formation in Salmonella enterica serovar Typhimurium by the periplasmic DsbA/DsbB oxidoreductase system requires the GGDEF-EAL domain protein STM3615. PloS one 9(8), e106095.
  146. Joo, H.-S., and Otto, M. (2012). Molecular basis of in vivo biofilm formation by bacterial pathogens. Chemistry & biology 19(12), 1503-1513.
  147. Newman, J.A., Rodrigues, C., and Lewis, R.J. (2013). Molecular basis of the activity of SinR protein, the master regulator of biofilm formation in Bacillus subtilis. Journal of Biological Chemistry 288(15), 10766-10778.
  148. Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular cloning: a laboratory manual. Cold spring harbor laboratory press.
  149. Mielich‐ Süss, B., and Lopez, D. (2015). Molecular mechanisms involved in Bacillus subtilis biofilm formation. Environmental microbiology 17(3), 555-565.
  150. Hölscher, T., Bartels, B., Lin, Y.-C., Gallegos-Monterrosa, R., Price-Whelan, A., Kolter, R., et al . (2015). Motility, chemotaxis and aerotaxis contribute to competitiveness during bacterial pellicle biofilm development. Journal of Molecular Biology 427(23), 3695-3708.
  151. Dahl, M.K., Msadek, T., Kunst, F., and Rapoport, G. (1991). Mutational analysis of the Bacillus subtilis DegU regulator and its phosphorylation by the DegS protein kinase. Journal of bacteriology 173(8), 2539-2547.
  152. Rubinstein, S.M., Kolodkin‐ Gal, I., Mcloon, A., Chai, L., Kolter, R., Losick, R., et al. (2012). Osmotic pressure can regulate matrix gene expression in Bacillus subtilis. Molecular microbiology 86(2), 426-436.
  153. Colvin, K.M., Alnabelseya, N., Baker, P., Whitney, J.C., Howell, P.L., and Parsek, M.R. (2013). PelA deacetylase activity is required for Pel polysaccharide synthesis in Pseudomonas aeruginosa. Journal of bacteriology 195(10), 2329-2339.
  154. Jennings, L.K., Storek, K.M., Ledvina, H.E., Coulon, C., Marmont, L.S., Sadovskaya, I., et al . (2015). Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix. Proceedings of the National Academy of Sciences 112(36), 11353-11358.
  155. Marlow, V.L., Porter, M., Hobley, L., Kiley, T.B., Swedlow, J.R., Davidson, F.A., et al . (2014). Phosphorylated DegU manipulates cell fate differentiation in the Bacillus subtilis biofilm. Journal of bacteriology 196(1), 16-27.
  156. Steinmetz, M., and Richter, R. (1994). Plasmids designed to alter the antibiotic resistance expressed by insertion mutations in Bacillus subtilis, through in vivo recombination. Gene 142(1), 79-83.
  157. Candela, T., and Fouet, A. (2006). Poly‐ gamma‐ glutamate in bacteria. Molecular microbiology 60(5), 1091-1098.
  158. Lupas, A., Van Dyke, M., and Stock, J. (1991). Predicting coiled coils from protein sequences. Science 252(5009), 1162.
  159. Kulshina, N., Baird, N.J., and Ferré-D'Amaré, A.R. (2009). Recognition of the bacterial second messenger cyclic diguanylate by its cognate riboswitch. Nature structural & molecular biology 16(12), 1212-1217.
  160. Ross, P., Weinhouse, H., Aloni, Y., Michaeli, D., Weinberger-Ohana, P., Mayer, R., et al. (1987). Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid. Nature 325(6101), 279-281.
  161. Stöver, A.G., and Driks, A. (1999a). Regulation of synthesis of the Bacillus subtilis transition-phase, sporeassociated antibacterial protein TasA. Journal of bacteriology 181(17), 5476-5481.
  162. McKew, B.A., Taylor, J.D., McGenity, T.J., and Underwood, G.J. (2011). Resistance and resilience of benthic biofilm communities from a temperate saltmarsh to desiccation and rewetting. The ISME journal 5(1), 30-41.
  163. Kolodkin-Gal, I., Elsholz, A.K., Muth, C., Girguis, P.R., Kolter, R., and Losick, R. (2013). Respiration control of multicellularity in Bacillus subtilis by a complex of the cytochrome chain with a membrane-embedded histidine kinase. Genes & development 27(8), 887-899.
  164. Zaccolo, M., Di Benedetto, G., Lissandron, V., Mancuso, L., Terrin, A., and Zamparo, I. (2006). Restricted diffusion of a freely diffusible second messenger: mechanisms underlying compartmentalized cAMP signalling. Portland Press Limited.
  165. Chai, Y., Kolter, R., and Losick, R. (2010). Reversal of an epigenetic switch governing cell chaining in Bacillus subtilis by protein instability. Molecular microbiology 78(1), 218-229.
  166. Robledo, M., Rivera, L., Jiménez-Zurdo, J.I., Rivas, R., Dazzo, F., Velázquez, E., et al. (2012). Role of Rhizobium endoglucanase CelC2 in cellulose biosynthesis and biofilm formation on plant roots and abiotic surfaces. Microbial cell factories 11(1), 125.
  167. Itoh, Y., Rice, J.D., Goller, C., Pannuri, A., Taylor, J., Meisner, J., et al . (2008). Roles of pgaABCD genes in synthesis, modification, and export of the Escherichia coli biofilm adhesin poly-β-1, 6-N-acetyl-Dglucosamine. Journal of bacteriology 190(10), 3670-3680.
  168. Boehm, A., Kaiser, M., Li, H., Spangler, C., Kasper, C.A., Ackermann, M., et al . (2010). Second messengermediated adjustment of bacterial swimming velocity. Cell 141(1), 107-116.
  169. Lodish, H., Berk, A., Zipursky, S.L., Matsudaira, P., Baltimore, D., and Darnell, J. (2000). Second Messengers. Molecular cell biology, Scientific American Books New York, 3 López, D., Vlamakis, H., and Kolter, R. (2010). Biofilms. Cold Spring Harbor perspectives in biology 2(7), a000398.
  170. Boehm, A., Steiner, S., Zaehringer, F., Casanova, A., Hamburger, F., Ritz, D., et al . (2009). Second messenger signalling governs Escherichia coli biofilm induction upon ribosomal stress. Molecular microbiology 72(6), 1500-1516.
  171. Stöver, A.G., and Driks, A. (1999b). Secretion, localization, and antibacterial activity of TasA, a Bacillus subtilis spore-associated protein. Journal of bacteriology 181(5), 1664-1672.
  172. Elsholz, A.K., Wacker, S.A., and Losick, R. (2014). Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase. Genes & development 28(15), 1710-1720.
  173. Krasteva, P.V., Giglio, K.M., and Sondermann, H. (2012). Sensing the messenger: The diverse ways that bacteria signal through c‐ di‐ GMP. Protein Science 21(7), 929-948.
  174. Maharaj, R., May, T.B., Shang-Kwei, W., and Chakrabarty, A.M. (1993). Sequence of the alg8 and alg44 genes involved in the synthesis of alginate by Pseudomonas aeruginosa. Gene 136(1), 267-269.
  175. Humphries, J., Xiong, L., Liu, J., Prindle, A., Yuan, F., Arjes, H.A., et al . (2017). Species-Independent Attraction to Biofilms through Electrical Signaling. Cell 168(1), 200-209. e212.
  176. Mullis, K., Faloona, F., Scharf, S., Saiki, R., Horn, G., and Erlich, H. (1986). Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction, in: Cold Spring Harbor symposia on quantitative biology: Cold Spring Harbor Laboratory Press, 263-273.
  177. Dahlstrom, K.M. (2016). Specificity in Signaling: Bacterial Decision-Making through the Cyclic Diguanylate Second Messenger. Dartmouth College.
  178. Omoike, A., and Chorover, J. (2004). Spectroscopic study of extracellular polymeric substances from Bacillus subtilis: Aqueous chemistry and adsorption effects. Biomacromolecules 5(4), 1219-1230.
  179. Herzberg, C., Weidinger, L.A.F., Dörrbecker, B., Hübner, S., Stülke, J., and Commichau, F.M. (2007). SPINE: a method for the rapid detection and analysis of protein-protein interactions in vivo. Proteomics 7(22), 4032-4035.
  180. Boylan, S.A., Redfield, A.R., Brody, M.S., and Price, C.W. (1993). Stress-induced activation of the sigma B transcription factor of Bacillus subtilis. Journal of bacteriology 175(24), 7931-7937.
  181. Navarro, M.V., De, N., Bae, N., Wang, Q., and Sondermann, H. (2009). Structural analysis of the GGDEFEAL domain-containing c-di-GMP receptor FimX. Structure 17(8), 1104-1116.
  182. Shin, J.S., Ryu, K.S., Ko, J., Lee, A., and Choi, B.S. (2011). Structural characterization reveals that a PilZ domain protein undergoes substantial conformational change upon binding to cyclic dimeric guanosine monophosphate. Protein Sci 20(2), 270-277.
  183. Benigar, E., Dogsa, I., Stopar, D., Jamnik, A., Cigić, I.K., and Tomšič, M. (2014). Structure and dynamics of a polysaccharide matrix: aqueous solutions of bacterial levan. Langmuir 30(14), 4172-4182.
  184. Willis, L.M., and Whitfield, C. (2013). Structure, biosynthesis, and function of bacterial capsular polysaccharides synthesized by ABC transporter-dependent pathways. Carbohydrate research 378, 35-44.
  185. Mills, E., Pultz, I.S., Kulasekara, H.D., and Miller, S.I. (2011). The bacterial second messenger c‐ di‐ GMP: mechanisms of signalling. Cellular microbiology 13(8), 1122-1129.
  186. Paul, K., Nieto, V., Carlquist, W.C., Blair, D.F., and Harshey, R.M. (2010). The c-di-GMP binding protein YcgR controls flagellar motor direction and speed to affect chemotaxis by a “backstop brake” mechanism. Molecular cell 38(1), 128-139.
  187. Linder, J.U., and Schultz, J.E. (2003). The class III adenylyl cyclases: multi-purpose signalling modules. Cell Signal 15(12), 1081-1089.
  188. Alzari, P.M., ne Souchon, H., and Dominguez, R. (1996). The crystal structure of endoglucanase CelA, a family 8 glycosyl hydrolase from Clostridium thermocellum. Structure 4(3), 265-275.
  189. Monds, R.D., and O'Toole, G.A. (2009). The developmental model of microbial biofilms: ten years of a paradigm up for review. Trends in microbiology 17(2), 73-87.
  190. Lindenberg, S., Klauck, G., Pesavento, C., Klauck, E., and Hengge, R. (2013). The EAL domain protein YciR acts as a trigger enzyme in ac‐ di‐ GMP signalling cascade in E. coli biofilm control. The EMBO journal 32(14), 2001-2014.
  191. Baraquet, C., Murakami, K., Parsek, M.R., and Harwood, C.S. (2012). The FleQ protein from Pseudomonas aeruginosa functions as both a repressor and an activator to control gene expression from the pel operon promoter in response to c-di-GMP. Nucleic acids research, gks384.
  192. Rao, F., Qi, Y., Chong, H.S., Kotaka, M., Li, B., Li, J., et al . (2009). The functional role of a conserved loop in EAL domain-based cyclic di-GMP-specific phosphodiesterase. Journal of bacteriology 191(15), 4722-4731.
  193. Mogk, A., Homuth, G., Scholz, C., Kim, L., Schmid, F.X., and Schumann, W. (1997). The GroE chaperonin machine is a major modulator of the CIRCE heat shock regulon of Bacillus subtilis. The EMBO Journal 16(15), 4579-4590.
  194. Aravind, L., and Koonin, E.V. (1998). The HD domain defines a new superfamily of metal-dependent phosphohydrolases. Trends in biochemical sciences 23(12), 469-472.
  195. York, L.M., Carminati, A., Mooney, S.J., Ritz, K., and Bennett, M.J. (2016). The holistic rhizosphere: integrating zones, processes, and semantics in the soil influenced by roots. Journal of experimental botany, erw108.
  196. Hubbard, C., McNamara, J.T., Azumaya, C., Patel, M.S., and Zimmer, J. (2012). The hyaluronan synthase catalyzes the synthesis and membrane translocation of hyaluronan. Journal of molecular biology 418(1), 21-31.
  197. Dahlstrom, K.M., Giglio, K.M., Sondermann, H., and O'Toole, G.A. (2016). The Inhibitory Site of a Diguanylate Cyclase Is a Necessary Element for Interaction and Signaling with an Effector Protein. Journal of bacteriology 198(11), 1595-1603.
  198. Conner, J.G., Zamorano-Sánchez, D., Park, J.H., Sondermann, H., and Yildiz, F.H. (2017). The ins and outs of cyclic di-GMP signaling in Vibrio cholerae. Current Opinion in Microbiology 36, 20-29.
  199. Johnston, E.B., Lewis, P.J., and Griffith, R. (2009). The interaction of Bacillus subtilis σA with RNA polymerase. Protein Science 18(11), 2287-2297.
  200. Alva, V., Nam, S.-Z., Söding, J., and Lupas, A.N. (2016). The MPI bioinformatics Toolkit as an integrative platform for advanced protein sequence and structure analysis. Nucleic acids research 44(W1), W410-W415.
  201. Ryjenkov, D.A., Simm, R., Römling, U., and Gomelsky, M. (2006). The PilZ domain is a receptor for the second messenger c-di-GMP: The PilZ domain protein Ycgr controls motility in enterobacteria. Journal of Biological Chemistry 281(41), 30310-30314.
  202. Pultz, I.S., Christen, M., Kulasekara, H.D., Kennard, A., Kulasekara, B., and Miller, S.I. (2012). The response threshold of Salmonella PilZ domain proteins is determined by their binding affinities for c‐ di‐ GMP. Molecular microbiology 86(6), 1424-1440.
  203. Wolfe, A.J., and Visick, K.L. (2010). The second messenger cyclic di-GMP. American Society for Microbiology Press.
  204. Molle, V., Fujita, M., Jensen, S.T., Eichenberger, P., González‐ Pastor, J.E., Liu, J.S., et al. (2003). The Spo0A regulon of Bacillus subtilis. Molecular microbiology 50(5), 1683-1701.
  205. Dunker, A.K., Oldfield, C.J., Meng, J., Romero, P., Yang, J.Y., Chen, J.W., et al . (2008). The unfoldomics decade: an update on intrinsically disordered proteins. BMC genomics 9(2), S1.
  206. Diethmaier, C., Newman, J.A., Kovács, Á.T., Kaever, V., Herzberg, C., Rodrigues, C., et al. (2014). The YmdB phosphodiesterase is a global regulator of late adaptive responses in Bacillus subtilis. Journal of bacteriology 196(2), 265-275.
  207. Jenal, U. (2013). Think globally, act locally: How bacteria integrate local decisions with their global cellular programme. The EMBO journal 32(14), 1972-1974.
  208. Paul, E., and Clark, F. (1989). Transformation of nitrogen between the organic and inorganic phase and to nitrate. Soil microbiology and biochemistry. Academic Press, San Diego, CA. USA, 131-146.

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