Integrative and quantitative view of the CtrA regulatory network in a stalked budding bacterium

Autoři: Oliver Leicht aff001;  Muriel C. F. van Teeseling aff001;  Gaël Panis aff002;  Celine Reif aff001;  Heiko Wendt aff001;  Patrick H. Viollier aff002;  Martin Thanbichler aff001
Působiště autorů: Department of Biology, University of Marburg, Marburg, Germany aff001;  Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics in Geneva (iGE3), Faculty of Medicine/CMU, University of Geneva, Geneve, Switzerland aff002;  Center for Synthetic Microbiology (SYNMIKRO), Marburg, Germany aff003;  Max Planck Institute for Terrestrial Microbiology, Marburg, Germany aff004
Vyšlo v časopise: Integrative and quantitative view of the CtrA regulatory network in a stalked budding bacterium. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008724
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008724


The Alphaproteobacteria show a remarkable diversity of cell cycle-dependent developmental patterns, which are governed by the conserved CtrA pathway. Its central component CtrA is a DNA-binding response regulator that is controlled by a complex two-component signaling network, mediating distinct transcriptional programs in the two offspring. The CtrA pathway has been studied intensively and was shown to consist of an upstream part that reads out the developmental state of the cell and a downstream part that integrates the upstream signals and mediates CtrA phosphorylation. However, the role of this circuitry in bacterial diversification remains incompletely understood. We have therefore investigated CtrA regulation in the morphologically complex stalked budding alphaproteobacterium Hyphomonas neptunium. Compared to relatives dividing by binary fission, H. neptunium shows distinct changes in the role and regulation of various pathway components. Most notably, the response regulator DivK, which normally links the upstream and downstream parts of the CtrA pathway, is dispensable, while downstream components such as the pseudokinase DivL, the histidine kinase CckA, the phosphotransferase ChpT and CtrA are essential. Moreover, CckA is compartmentalized to the nascent bud without forming distinct polar complexes and CtrA is not regulated at the level of protein abundance. We show that the downstream pathway controls critical functions such as replication initiation, cell division and motility. Quantification of the signal flow through different nodes of the regulatory cascade revealed that the CtrA pathway is a leaky pipeline and must involve thus-far unidentified factors. Collectively, the quantitative system-level analysis of CtrA regulation in H. neptunium points to a considerable evolutionary plasticity of cell cycle regulation in alphaproteobacteria and leads to hypotheses that may also hold in well-established model organisms such as Caulobacter crescentus.

Klíčová slova:

Cell cycle and cell division – Cell polarity – Gene regulation – Phosphorylation – Regulator genes – Regulons – Neptunium – Caulobacter crescentus


1. Esser D, Hoffmann L, Pham TK, Brasen C, Qiu W, Wright PC, et al. Protein phosphorylation and its role in archaeal signal transduction. FEMS Microbiol Rev. 2016;40(5):625–647. doi: 10.1093/femsre/fuw020 27476079.

2. Kobir A, Shi L, Boskovic A, Grangeasse C, Franjevic D, Mijakovic I. Protein phosphorylation in bacterial signal transduction. Biochim Biophys Acta. 2011;1810(10):989–994. doi: 10.1016/j.bbagen.2011.01.006 21266190.

3. Kyriakis JM. In the beginning, there was protein phosphorylation. J Biol Chem. 2014;289(14):9460–9462. doi: 10.1074/jbc.R114.557926 24554697.

4. Hoch JA. Two-component and phosphorelay signal transduction. Curr Opin Microbiol. 2000;3(2):165–170. doi: 10.1016/s1369-5274(00)00070-9 10745001.

5. Stock AM, Robinson VL, Goudreau PN. Two-component signal transduction. Annu Rev Biochem. 2000;69:183–215. doi: 10.1146/annurev.biochem.69.1.183 10966457.

6. Higgins D, Dworkin J. Recent progress in Bacillus subtilis sporulation. FEMS Microbiol Rev. 2012;36(1):131–148. doi: 10.1111/j.1574-6976.2011.00310.x 22091839.

7. Sarwar Z, Garza AG. Two-component signal transduction systems that regulate the temporal and spatial expression of Myxococcus xanthus sporulation genes. J Bacteriol. 2016;198(3):377–385. doi: 10.1128/JB.00474-15 26369581.

8. Lasker K, Mann TH, Shapiro L. An intracellular compass spatially coordinates cell cycle modules in Caulobacter crescentus. Curr Opin Microbiol. 2016;33:131–139. doi: 10.1016/j.mib.2016.06.007 27517351.

9. Tsokos CG, Laub MT. Polarity and cell fate asymmetry in Caulobacter crescentus. Curr Opin Microbiol. 2012;15(6):744–750. doi: 10.1016/j.mib.2012.10.011 23146566.

10. Cserti E, Rosskopf S, Chang YW, Eisheuer S, Selter L, Shi J, et al. Dynamics of the peptidoglycan biosynthetic machinery in the stalked budding bacterium Hyphomonas neptunium. Mol Microbiol. 2017;103(5):875–895. doi: 10.1111/mmi.13593 27997718.

11. Randich AM, Brun YV. Molecular mechanisms for the evolution of bacterial morphologies and growth modes. Front Microbiol. 2015;6:580. doi: 10.3389/fmicb.2015.00580 26106381.

12. Curtis PD, Quardokus EM, Lawler ML, Guo X, Klein D, Chen JC, et al. The scaffolding and signalling functions of a localization factor impact polar development. Mol Microbiol. 2012;84(4):712–735. doi: 10.1111/j.1365-2958.2012.08055.x 22512778.

13. Domian IJ, Quon KC, Shapiro L. Cell type-specific phosphorylation and proteolysis of a transcriptional regulator controls the G1-to-S transition in a bacterial cell cycle. Cell. 1997;90(3):415–424. doi: 10.1016/s0092-8674(00)80502-4 9267022.

14. Quon KC, Marczynski GT, Shapiro L. Cell cycle control by an essential bacterial two-component signal transduction protein. Cell. 1996;84(1):83–93. doi: 10.1016/s0092-8674(00)80995-2 8548829.

15. Laub MT, Chen SL, Shapiro L, McAdams HH. Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle. Proc Natl Acad Sci U S A. 2002;99(7):4632–4637. doi: 10.1073/pnas.062065699 11930012.

16. Quon KC, Yang B, Domian IJ, Shapiro L, Marczynski GT. Negative control of bacterial DNA replication by a cell cycle regulatory protein that binds at the chromosome origin. Proc Natl Acad Sci U S A. 1998;95(1):120–125. doi: 10.1073/pnas.95.1.120 9419339.

17. Collier J. Cell cycle control in Alphaproteobacteria. Curr Opin Microbiol. 2016;30:107–113. doi: 10.1016/j.mib.2016.01.010 26871482.

18. Collier J, Murray SR, Shapiro L. DnaA couples DNA replication and the expression of two cell cycle master regulators. EMBO J. 2006;25(2):346–356. doi: 10.1038/sj.emboj.7600927 16395331.

19. Hottes AK, Shapiro L, McAdams HH. DnaA coordinates replication initiation and cell cycle transcription in Caulobacter crescentus. Mol Microbiol. 2005;58(5):1340–1353. doi: 10.1111/j.1365-2958.2005.04912.x 16313620.

20. Haakonsen DL, Yuan AH, Laub MT. The bacterial cell cycle regulator GcrA is a σ70 cofactor that drives gene expression from a subset of methylated promoters. Genes Dev. 2015;29(21):2272–2286. doi: 10.1101/gad.270660.115 26545812.

21. Holtzendorff J, Hung D, Brende P, Reisenauer A, Viollier PH, McAdams HH, et al. Oscillating global regulators control the genetic circuit driving a bacterial cell cycle. Science. 2004;304(5673):983–987. doi: 10.1126/science.1095191 15087506.

22. Biondi EG, Reisinger SJ, Skerker JM, Arif M, Perchuk BS, Ryan KR, et al. Regulation of the bacterial cell cycle by an integrated genetic circuit. Nature. 2006;444(7121):899–904. doi: 10.1038/nature05321 17136100.

23. Jacobs C, Domian IJ, Maddock JR, Shapiro L. Cell cycle-dependent polar localization of an essential bacterial histidine kinase that controls DNA replication and cell division. Cell. 1999;97(1):111–120. doi: 10.1016/s0092-8674(00)80719-9 10199407.

24. Chen YE, Tsokos CG, Biondi EG, Perchuk BS, Laub MT. Dynamics of two phosphorelays controlling cell cycle progression in Caulobacter crescentus. J Bacteriol. 2009;191(24):7417–7429. doi: 10.1128/JB.00992-09 19783630.

25. Tsokos CG, Perchuk BS, Laub MT. A dynamic complex of signaling proteins uses polar localization to regulate cell-fate asymmetry in Caulobacter crescentus. Dev Cell. 2011;20(3):329–341. doi: 10.1016/j.devcel.2011.01.007 21397844.

26. Angelastro PS, Sliusarenko O, Jacobs-Wagner C. Polar localization of the CckA histidine kinase and cell cycle periodicity of the essential master regulator CtrA in Caulobacter crescentus. J Bacteriol. 2010;192(2):539–552. doi: 10.1128/JB.00985-09 19897656.

27. Iniesta AA, Hillson NJ, Shapiro L. Cell pole-specific activation of a critical bacterial cell cycle kinase. Proc Natl Acad Sci U S A. 2010;107(15):7012–7017. doi: 10.1073/pnas.1001767107 20351295.

28. Radhakrishnan SK, Thanbichler M, Viollier PH. The dynamic interplay between a cell fate determinant and a lysozyme homolog drives the asymmetric division cycle of Caulobacter crescentus. Genes Dev. 2008;22(2):212–225. doi: 10.1101/gad.1601808 18198338.

29. Wheeler RT, Shapiro L. Differential localization of two histidine kinases controlling bacterial cell differentiation. Mol Cell. 1999;4(5):683–694. doi: 10.1016/s1097-2765(00)80379-2 10619016.

30. Ohta N, Lane T, Ninfa EG, Sommer JM, Newton A. A histidine protein kinase homologue required for regulation of bacterial cell division and differentiation. Proc Natl Acad Sci U S A. 1992;89(21):10297–10301. doi: 10.1073/pnas.89.21.10297 1438215.

31. Abel S, Bucher T, Nicollier M, Hug I, Kaever V, Abel Zur Wiesch P, et al. Bi-modal distribution of the second messenger c-di-GMP controls cell fate and asymmetry during the caulobacter cell cycle. PLoS Genet. 2013;9(9):e1003744. doi: 10.1371/journal.pgen.1003744 24039597.

32. Lori C, Ozaki S, Steiner S, Bohm R, Abel S, Dubey BN, et al. Cyclic di-GMP acts as a cell cycle oscillator to drive chromosome replication. Nature. 2015;523(7559):236–239. doi: 10.1038/nature14473 25945741.

33. Hinz AJ, Larson DE, Smith CS, Brun YV. The Caulobacter crescentus polar organelle development protein PodJ is differentially localized and is required for polar targeting of the PleC development regulator. Mol Microbiol. 2003;47(4):929–941. doi: 10.1046/j.1365-2958.2003.03349.x 12581350.

34. Viollier PH, Sternheim N, Shapiro L. Identification of a localization factor for the polar positioning of bacterial structural and regulatory proteins. Proc Natl Acad Sci U S A. 2002;99(21):13831–13836. doi: 10.1073/pnas.182411999 12370432.

35. Jenal U, Fuchs T. An essential protease involved in bacterial cell-cycle control. EMBO J. 1998;17(19):5658–5669. doi: 10.1093/emboj/17.19.5658 9755166.

36. McGrath PT, Iniesta AA, Ryan KR, Shapiro L, McAdams HH. A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator. Cell. 2006;124(3):535–547. doi: 10.1016/j.cell.2005.12.033 16469700.

37. Iniesta AA, McGrath PT, Reisenauer A, McAdams HH, Shapiro L. A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression. Proc Natl Acad Sci U S A. 2006;103(29):10935–10940. doi: 10.1073/pnas.0604554103 16829582.

38. Joshi KK, Berge M, Radhakrishnan SK, Viollier PH, Chien P. An adaptor hierarchy regulates proteolysis during a bacterial cell cycle. Cell. 2015;163(2):419–431. doi: 10.1016/j.cell.2015.09.030 26451486.

39. Duerig A, Abel S, Folcher M, Nicollier M, Schwede T, Amiot N, et al. Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression. Genes Dev. 2009;23(1):93–104. doi: 10.1101/gad.502409 19136627.

40. Ozaki S, Schalch-Moser A, Zumthor L, Manfredi P, Ebbensgaard A, Schirmer T, et al. Activation and polar sequestration of PopA, a c-di-GMP effector protein involved in Caulobacter crescentus cell cycle control. Mol Microbiol. 2014;94(3):580–594. doi: 10.1111/mmi.12777 25171231.

41. Barnett MJ, Hung DY, Reisenauer A, Shapiro L, Long SR. A homolog of the CtrA cell cycle regulator is present and essential in Sinorhizobium meliloti. J Bacteriol. 2001;183(10):3204–3210. doi: 10.1128/JB.183.10.3204-3210.2001 11325950.

42. Bellefontaine AF, Pierreux CE, Mertens P, Vandenhaute J, Letesson JJ, de Bolle X. Plasticity of a transcriptional regulation network among alpha-proteobacteria is supported by the identification of CtrA targets in Brucella abortus. Mol Microbiol. 2002;43(4):945–960. doi: 10.1046/j.1365-2958.2002.02777.x 11929544.

43. Brown PJ, de Pedro MA, Kysela DT, Van der Henst C, Kim J, de Bolle X, et al. Polar growth in the Alphaproteobacterial order Rhizobiales. Proc Natl Acad Sci U S A. 2012;109(5):1697–1701. doi: 10.1073/pnas.1114476109 22307633.

44. Kim J, Heindl JE, Fuqua C. Coordination of division and development influences complex multicellular behavior in Agrobacterium tumefaciens. PLoS One. 2013;8(2):e56682. doi: 10.1371/journal.pone.0056682 23437210.

45. Bird TH, MacKrell A. A CtrA homolog affects swarming motility and encystment in Rhodospirillum centenum. Arch Microbiol. 2011;193(6):451–459. doi: 10.1007/s00203-011-0676-y 21243338.

46. Francez-Charlot A, Kaczmarczyk A, Vorholt JA. The branched CcsA/CckA-ChpT-CtrA phosphorelay of Sphingomonas melonis controls motility and biofilm formation. Mol Microbiol. 2015;97(1):47–63. doi: 10.1111/mmi.13011 25825287.

47. Greene SE, Brilli M, Biondi EG, Komeili A. Analysis of the CtrA pathway in Magnetospirillum reveals an ancestral role in motility in Alphaproteobacteria. J Bacteriol. 2012;194(11):2973–2986. doi: 10.1128/JB.00170-12 22467786.

48. Lang AS, Beatty JT. Genetic analysis of a bacterial genetic exchange element: the gene transfer agent of Rhodobacter capsulatus. Proc Natl Acad Sci U S A. 2000;97(2):859–864. doi: 10.1073/pnas.97.2.859 10639170.

49. Jung A, Eisheuer S, Cserti E, Leicht O, Strobel W, Möll A, et al. Molecular toolbox for genetic manipulation of the stalked budding bacterium Hyphomonas neptunium. Appl Environ Microbiol. 2015;81(2):736–744. doi: 10.1128/AEM.03104-14 25398860.

50. Leifson E. Hyphomicrobium neptunium sp. n. Antonie Van Leeuwenhoek. 1964;30:249–256. doi: 10.1007/bf02046730 14221685.

51. Badger JH, Eisen JA, Ward NL. Genomic analysis of Hyphomonas neptunium contradicts 16S rRNA gene-based phylogenetic analysis: implications for the taxonomy of the orders ' Rhodobacterales ' and Caulobacterales . Int J Syst Evol Microbiol. 2005;55(Pt 3):1021–1026. doi: 10.1099/ijs.0.63510–0 15879228.

52. Hirsch P. Budding bacteria. Annu Rev Microbiol. 1974;28(0):391–444. doi: 10.1146/annurev.mi.28.100174.002135 4611332.

53. Moore RL. The biology of Hyphomicrobium and other prosthecate, budding bacteria. Annu Rev Microbiol. 1981;35:567–594. doi: 10.1146/annurev.mi.35.100181.003031 6170249.

54. Hecht GB, Lane T, Ohta N, Sommer JM, Newton A. An essential single domain response regulator required for normal cell division and differentiation in Caulobacter crescentus. EMBO J. 1995;14(16):3915–3924. 7664732.

55. Sommer JM, Newton A. Pseudoreversion analysis indicates a direct role of cell division genes in polar morphogenesis and differentiation in Caulobacter crescentus. Genetics. 1991;129(3):623–630. 1752411.

56. Ely B, Croft RH, Gerardot CJ. Genetic mapping of genes required for motility in Caulobacter crescentus. Genetics. 1984;108(3):523–532. 6437899.

57. Childers WS, Xu Q, Mann TH, Mathews II, Blair JA, Deacon AM, et al. Cell fate regulation governed by a repurposed bacterial histidine kinase. PLoS Biol. 2014;12(10):e1001979. doi: 10.1371/journal.pbio.1001979 25349992.

58. Deich J, Judd EM, McAdams HH, Moerner WE. Visualization of the movement of single histidine kinase molecules in live Caulobacter cells. Proc Natl Acad Sci U S A. 2004;101(45):15921–15926. doi: 10.1073/pnas.0404200101 15522969.

59. Brassinga AK, Siam R, McSween W, Winkler H, Wood D, Marczynski GT. Conserved response regulator CtrA and IHF binding sites in the alpha-proteobacteria Caulobacter crescentus and Rickettsia prowazekii chromosomal replication origins. J Bacteriol. 2002;184(20):5789–5799. doi: 10.1128/JB.184.20.5789-5799.2002 12270838.

60. Brilli M, Fondi M, Fani R, Mengoni A, Ferri L, Bazzicalupo M, et al. The diversity and evolution of cell cycle regulation in alpha-proteobacteria: a comparative genomic analysis. BMC Syst Biol. 2010;4:52. doi: 10.1186/1752-0509-4-52 20426835.

61. Francis N, Poncin K, Fioravanti A, Vassen V, Willemart K, Ong TA, et al. CtrA controls cell division and outer membrane composition of the pathogen Brucella abortus. Mol Microbiol. 2017;103(5):780–797. doi: 10.1111/mmi.13589 27893179.

62. Mignolet J, Panis G, Viollier PH. More than a Tad: spatiotemporal control of Caulobacter pili. Curr Opin Microbiol. 2018;42:79–86. doi: 10.1016/j.mib.2017.10.017 29161615.

63. Domian IJ, Reisenauer A, Shapiro L. Feedback control of a master bacterial cell-cycle regulator. Proc Natl Acad Sci U S A. 1999;96(12):6648–6653. doi: 10.1073/pnas.96.12.6648 10359766.

64. Gora KG, Tsokos CG, Chen YE, Srinivasan BS, Perchuk BS, Laub MT. A cell-type-specific protein-protein interaction modulates transcriptional activity of a master regulator in Caulobacter crescentus. Mol Cell. 2010;39(3):455–467. doi: 10.1016/j.molcel.2010.06.024 20598601.

65. Tan MH, Kozdon JB, Shen X, Shapiro L, McAdams HH. An essential transcription factor, SciP, enhances robustness of Caulobacter cell cycle regulation. Proc Natl Acad Sci U S A. 2010;107(44):18985–18990. doi: 10.1073/pnas.1014395107 20956288.

66. Jung A, Rassbach A, Pulpetta RL, van Teeseling MCF, Heinrich K, Sobetzko P, et al. Two-step chromosome segregation in the stalked budding bacterium Hyphomonas neptunium. Nat Commun. 2019;10(1):3290. doi: 10.1038/s41467-019-11242-5 31337764.

67. Pini F, De Nisco NJ, Ferri L, Penterman J, Fioravanti A, Brilli M, et al. Cell cycle control by the master regulator CtrA in Sinorhizobium meliloti. PLoS Genet. 2015;11(5):e1005232. doi: 10.1371/journal.pgen.1005232 25978424.

68. Willett JW, Herrou J, Briegel A, Rotskoff G, Crosson S. Structural asymmetry in a conserved signaling system that regulates division, replication, and virulence of an intracellular pathogen. Proc Natl Acad Sci U S A. 2015;112(28):E3709–3718. doi: 10.1073/pnas.1503118112 26124143.

69. Fields AT, Navarrete CS, Zare AZ, Huang Z, Mostafavi M, Lewis JC, et al. The conserved polarity factor podJ1 impacts multiple cell envelope-associated functions in Sinorhizobium meliloti. Mol Microbiol. 2012;84(5):892–920. doi: 10.1111/j.1365-2958.2012.08064.x 22553970.

70. Pini F, Frage B, Ferri L, De Nisco NJ, Mohapatra SS, Taddei L, et al. The DivJ, CbrA and PleC system controls DivK phosphorylation and symbiosis in Sinorhizobium meliloti. Mol Microbiol. 2013;90(1):54–71. doi: 10.1111/mmi.12347 23909720.

71. Chen JC, Hottes AK, McAdams HH, McGrath PT, Viollier PH, Shapiro L. Cytokinesis signals truncation of the PodJ polarity factor by a cell cycle-regulated protease. EMBO J. 2006;25(2):377–386. doi: 10.1038/sj.emboj.7600935 16395329.

72. Jacobs C, Ausmees N, Cordwell SJ, Shapiro L, Laub MT. Functions of the CckA histidine kinase in Caulobacter cell cycle control. Mol Microbiol. 2003;47(5):1279–1290. Epub 2003/02/27. doi: 10.1046/j.1365-2958.2003.03379.x 12603734.

73. Paul R, Weiser S, Amiot NC, Chan C, Schirmer T, Giese B, et al. Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain. Genes Dev. 2004;18(6):715–727. doi: 10.1101/gad.289504 15075296.

74. Aldridge P, Jenal U. Cell cycle-dependent degradation of a flagellar motor component requires a novel-type response regulator. Mol Microbiol. 1999;32(2):379–391. doi: 10.1046/j.1365-2958.1999.01358.x 10231493.

75. Hecht GB, Newton A. Identification of a novel response regulator required for the swarmer-to-stalked-cell transition in Caulobacter crescentus. J Bacteriol. 1995;177(21):6223–6229. doi: 10.1128/jb.177.21.6223-6229.1995 7592388.

76. Sanselicio S, Berge M, Theraulaz L, Radhakrishnan SK, Viollier PH. Topological control of the Caulobacter cell cycle circuitry by a polarized single-domain PAS protein. Nat Commun. 2015;6:7005. doi: 10.1038/ncomms8005 25952018.

77. Lasker K, von Diezmann L, Zhou X, Ahrens DG, Mann TH, Moerner WE, et al. Selective sequestration of signalling proteins in a membraneless organelle reinforces the spatial regulation of asymmetry in Caulobacter crescentus. Nat Microbiol. 2020; doi: 10.1038/s41564-019-0647-7 31959967.

78. Mann TH, Childers WS, Blair JA, Eckart MR, Shapiro L. A cell cycle kinase with tandem sensory PAS domains integrates cell fate cues. Nat Commun. 2016;7:11454. doi: 10.1038/ncomms11454 27117914.

79. Chen YE, Tropini C, Jonas K, Tsokos CG, Huang KC, Laub MT. Spatial gradient of protein phosphorylation underlies replicative asymmetry in a bacterium. Proc Natl Acad Sci U S A. 2011;108(3):1052–1057. doi: 10.1073/pnas.1015397108 21191097.

80. Tropini C, Rabbani N, Huang KC. Physical constraints on the establishment of intracellular spatial gradients in bacteria. BMC Biophys. 2012;5:17. doi: 10.1186/2046-1682-5-17 22931750.

81. Reisenauer A, Quon K, Shapiro L. The CtrA response regulator mediates temporal control of gene expression during the Caulobacter cell cycle. J Bacteriol. 1999;181(8):2430–2439. 10198005.

82. Siam R, Marczynski GT. Cell cycle regulator phosphorylation stimulates two distinct modes of binding at a chromosome replication origin. EMBO J. 2000;19(5):1138–1147. doi: 10.1093/emboj/19.5.1138 10698954.

83. Siam R, Marczynski GT. Glutamate at the phosphorylation site of response regulator CtrA provides essential activities without increasing DNA binding. Nucleic Acids Res. 2003;31(6):1775–1779. doi: 10.1093/nar/gkg271 12626719.

84. Evinger M, Agabian N. Envelope-associated nucleoid from Caulobacter crescentus stalked and swarmer cells. J Bacteriol. 1977;132(1):294–301. 334726.

85. Meisenzahl AC, Shapiro L, Jenal U. Isolation and characterization of a xylose-dependent promoter from Caulobacter crescentus. J Bacteriol. 1997;179(3):592–600. doi: 10.1128/jb.179.3.592-600.1997 9006009.

86. Thanbichler M, Shapiro L. MipZ, a spatial regulator coordinating chromosome segregation with cell division in Caulobacter. Cell. 2006;126(1):147–162. doi: 10.1016/j.cell.2006.05.038 16839883.

87. Gilchrist A, Smit J. Transformation of freshwater and marine caulobacters by electroporation. J Bacteriol. 1991;173(2):921–925. doi: 10.1128/jb.173.2.921-925.1991 1987172.

88. Huang L. A new mechanistic growth model for simultaneous determination of lag phase duration and exponential growth rate and a new Bĕlehdrádek-type model for evaluating the effect of temperature on growth rate. Food Microbiol. 2011;28(4):770–776. doi: 10.1016/ 21511137.

89. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–675. doi: 10.1038/nmeth.2089 22930834.

90. Karimova G, Pidoux J, Ullmann A, Ladant D. A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A. 1998;95(10):5752–5756. doi: 10.1073/pnas.95.10.5752 9576956.

91. Skerker JM, Prasol MS, Perchuk BS, Biondi EG, Laub MT. Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis. PLoS Biol. 2005;3(10):e334. doi: 10.1371/journal.pbio.0030334 16176121.

92. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biology. 2008;9:R137. doi: 10.1186/gb-2008-9-9-r137 18798982

93. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, et al. MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 2009;37:W202–208. doi: 10.1093/nar/gkp335 19458158.

94. Mao F, Dam P, Chou J, Olman V, Xu Y. DOOR: a database for prokaryotic operons. Nucleic Acids Res. 2009;37(Database issue):D459–463. doi: 10.1093/nar/gkn757 18988623.

95. de Hoon MJ, Imoto S, Nolan J, Miyano S. Open source clustering software. Bioinformatics. 2004;20(9):1453–1454. doi: 10.1093/bioinformatics/bth078 14871861.

96. Saldanha AJ. Java Treeview–extensible visualization of microarray data. Bioinformatics. 2004;20(17):3246–3248. doi: 10.1093/bioinformatics/bth349 15180930

97. Wali TM, Hudson GR, Danald DA, Weiner RM. Timing of swarmer cell cycle morphogenesis and macromolecular synthesis by Hyphomicrobium neptunium in synchronous culture. J Bacteriol. 1980;144(1):406–412. 6158509.

98. Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M. KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 2016;44(D1):D457–462. doi: 10.1093/nar/gkv1070 26476454.

99. Consortium TU. UniProt: the universal protein knowledgebase. Nucleic Acids Res. 2017;45(D1):D158–169. doi: 10.1093/nar/gkw1099 27899622.

100. Letunic I, Bork P. 20 years of the SMART protein domain annotation resource. Nucleic Acids Res. 2018;46(D1):D493–496. doi: 10.1093/nar/gkx922 29040681.

101. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2 2231712.

102. Overmars L, Kerkhoven R, Siezen RJ, Francke C. MGcV: the microbial genomic context viewer for comparative genome analysis. BMC Genomics. 2013;14:209. doi: 10.1186/1471-2164-14-209 23547764.

Genetika Reprodukční medicína

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PLOS Genetics

2020 Číslo 4

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