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  • Review Article
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Temporal and spatial oscillations in bacteria

Nature Reviews Microbiology volume 9, pages 565–577 (2011)Cite this article

Subjects

Key Points

  • Bacteria contain three types of signal transduction pathway that are wired to give rise to three different types of output in response to perturbations: a homeostatic response, a bistable response and an oscillatory output.

  • A biological system giving rise to an oscillatory output consists of three parts: the oscillator, which is the biochemical machinery that generates the oscillatory output; an input pathway (or pathways) that regulates the oscillator in response to external or internal signals; and output pathways that couple information about the state of the oscillator to downstream targets in order to generate the oscillatory output.

  • Bacteria contain two different types of oscillator. Temporal oscillators incorporate temporal variations in the accumulation or activity of a protein (or proteins) and drive temporal cycles such as the cell cycle and the circadian cycle. Spatial oscillators incorporate temporal variations in the localization of a protein (or proteins) without changes in protein accumulation or activity being necessary. These oscillators define subcellular positions, such as the sites of cell division and of chromosome and plasmid positioning, or establish and maintain cell polarity.

  • The cell cycle oscillator of Caulobacter crescentus and the circadian oscillator of Synechococcus elongatus are the two best understood temporal oscillators in bacteria. Both oscillators contain feedback loops that are essential for generating the oscillations. The cell cycle oscillator is built on circuits incorporating a toggle switch that is flipped to the 'on' state in a positive feedback loop and to the 'off' state in a delayed negative feedback loop. The circadian oscillator is built on interactions that involve a negative feedback loop which gives rise to two alternative states.

  • The cell division oscillator and the DNA segregation oscillator in Escherichia coli are spatial oscillators that define the site of cell division and segregate plasmids to daughter cells, respectively. These two oscillators are built on post-translational interactions involving, on the one part, homologous proteins that bind cooperatively to a scaffold (MinD and ParA binding to the membrane and the chromosome, respectively) and, on the other part, analogous proteins (MinE and ParB, respectively) that act in a delayed negative feedback loop to drive MinD and ParA off their respective scaffolds.

  • The spatial cell polarity oscillator in Myxococcus xanthus establishes the leading–lagging cell polarity axis and allows the occasional, cell cycle-independent inversion of this axis. In this system, the irregular oscillations are established by a double-negative feedback loop involving the two main regulators, similar to the loop that is found in a toggle switch, in which the system is flipped between two states.

  • Both types of oscillators incorporate a negative feedback loop, which can be embedded in different regulatory contexts to give each oscillator its particular characteristics. Similarly, individual oscillators have evolved their specific designs using different proteins that act at different levels.

Abstract

Oscillations pervade biological systems at all scales. In bacteria, oscillations control fundamental processes, including gene expression, cell cycle progression, cell division, DNA segregation and cell polarity. Oscillations are generated by biochemical oscillators that incorporate the periodic variation in a parameter over time to generate an oscillatory output. Temporal oscillators incorporate the periodic accumulation or activity of a protein to drive temporal cycles such as the cell and circadian cycles. Spatial oscillators incorporate the periodic variation in the localization of a protein to define subcellular positions such as the site of cell division and the localization of DNA. In this Review, we focus on the mechanisms of oscillators and discuss the design principles of temporal and spatial oscillatory systems.

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Figure 1: The Caulobacter crescentus cell cycle oscillator.
Figure 2: The Synechococcus elongatus circadian oscillator.
Figure 3: The cell division and DNA segregation oscillators in Escherichia coli.
Figure 4: The cell polarity oscillator in Myxococcus xanthus.

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References

  1. Grobbelaar, N., Huang, T., Lin, H. & Chow, T. Dinitrogen-fixing endogenous rhythm in Synechococcus RF-1. FEMS Microbiol. Lett. 37, 173–177 (1986).

    Article  CAS  Google Scholar 

  2. Liu, Y. et al. Circadian orchestration of gene expression in cyanobacteria. Genes Dev. 9, 1469–1478 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Mitsui, A. et al. Strategy by which nitrogen-fixing unicellular cyanobacteria grow photoautotrophically. Nature 323, 720–722 (1986).

    Article  CAS  Google Scholar 

  4. Goldbeter, A. Biological rhythms: clocks for all times. Curr. Biol. 18, R751–R753 (2008).

    Article  CAS  PubMed  Google Scholar 

  5. Murray, A. W. Recycling the cell cycle: cyclins revisited. Cell 116, 221–234 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Laub, M. T., Shapiro, L. & McAdams, H. H. Systems biology of Caulobacter. Annu. Rev. Genet. 41, 429–441 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Jenal, U. The role of proteolysis in the Caulobacter crescentus cell cycle and development. Res. Microbiol. 160, 687–695 (2009).

    Article  CAS  PubMed  Google Scholar 

  8. McAdams, H. H. & Shapiro, L. System-level design of bacterial cell cycle control. FEBS Lett. 583, 3984–3991 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Laub, M. T., McAdams, H. H., Feldblyum, T., Fraser, C. M. & Shapiro, L. Global analysis of the genetic network controlling a bacterial cell cycle. Science 290, 2144–2148 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Collier, J., McAdams, H. H. & Shapiro, L. A DNA methylation ratchet governs progression through a bacterial cell cycle. Proc. Natl Acad. Sci. USA 104, 17111–17116 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Collier, J., Murray, S. R. & Shapiro, L. DnaA couples DNA replication and the expression of two cell cycle master regulators. EMBO J. 25, 346–356 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Holtzendorff, J. et al. Oscillating global regulators control the genetic circuit driving a bacterial cell cycle. Science 304, 983–987 (2004). This paper identifies GcrA and provides a first outline of an oscillating genetic circuit, which is part of the cell cycle oscillator in C. crescentus.

    Article  CAS  PubMed  Google Scholar 

  13. Quon, K. C., Marczynski, G. T. & Shapiro, L. Cell cycle control by an essential bacterial two-component signal transduction protein. Cell 84, 83–93 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Domian, I. J., Quon, K. C. & Shapiro, L. Cell type-specific phosphorylation and proteolysis of a transcriptional regulator controls the G1-to-S transition in a bacterial cell cycle. Cell 90, 415–424 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Shen, X. et al. Architecture and inherent robustness of a bacterial cell-cycle control system. Proc. Natl Acad. Sci. USA 105, 11340–11345 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Quon, K. C., Yang, B., Domian, I. J., Shapiro, L. & Marczynski, G. T. Negative control of bacterial DNA replication by a cell cycle regulatory protein that binds at the chromosome origin. Proc. Natl Acad. Sci. USA 95, 120–125 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Domian, I. J., Reisenauer, A. & Shapiro, L. Feedback control of a master bacterial cell-cycle regulator. Proc. Natl Acad. Sci. USA 96, 6648–6653 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Stephens, C., Reisenauer, A., Wright, R. & Shapiro, L. A cell cycle-regulated bacterial DNA methyltransferase is essential for viability. Proc. Natl Acad. Sci. USA 93, 1210–1214 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wright, R., Stephens, C., Zweiger, G., Shapiro, L. & Alley, M. R. Caulobacter Lon protease has a critical role in cell-cycle control of DNA methylation. Genes Dev. 10, 1532–1542 (1996).

    Article  CAS  PubMed  Google Scholar 

  20. Jacobs, C., Domian, I. J., Maddock, J. R. & Shapiro, L. Cell cycle-dependent polar localization of an essential bacterial histidine kinase that controls DNA replication and cell division. Cell 97, 111–120 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Biondi, E. G. et al. Regulation of the bacterial cell cycle by an integrated genetic circuit. Nature 444, 899–904 (2006). This article identifies the DivK–CckA–ChpT–CtrA phosphorelay and CpdR in the cell cycle oscillator, and shows that CtrA triggers its own destruction by promoting cell division and inducing DivK synthesis.

    Article  CAS  PubMed  Google Scholar 

  22. Iniesta, A. A., McGrath, P. T., Reisenauer, A., McAdams, H. H. & 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. USA 103, 10935–10940 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. McGrath, P. T., Iniesta, A. A., Ryan, K. R., Shapiro, L. & McAdams, H. H. A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator. Cell 124, 535–547 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Wheeler, R. T. & Shapiro, L. Differential localization of two histidine kinases controlling bacterial cell differentiation. Mol. Cell 4, 683–694 (1999).

    Article  CAS  PubMed  Google Scholar 

  25. Paul, R. et al. Allosteric regulation of histidine kinases by their cognate response regulator determines cell fate. Cell 133, 452–461 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Matroule, J. Y., Lam, H., Burnette, D. T. & Jacobs-Wagner, C. Cytokinesis monitoring during development: rapid pole-to-pole shuttling of a signaling protein by localized kinase and phosphatase in Caulobacter. Cell 118, 579–590 (2004).

    Article  CAS  PubMed  Google Scholar 

  27. Duerig, A. et al. Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression. Genes Dev. 23, 93–104 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Brazhnik, P. & Tyson, J. J. Cell cycle control in bacteria and yeast: a case of convergent evolution? Cell Cycle 5, 522–529 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Li, S., Brazhnik, P., Sobral, B. & Tyson, J. J. A quantitative study of the division cycle of Caulobacter crescentus stalked cells. PLoS Comput. Biol. 4, e9 (2008).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Li, S., Brazhnik, P., Sobral, B. & Tyson, J. J. Temporal controls of the asymmetric cell division cycle in Caulobacter crescentus. PLoS Comput. Biol. 5, e1000463 (2009).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Wijnen, H. & Young, M. W. Interplay of circadian clocks and metabolic rhythms. Annu. Rev. Genet. 40, 409–448 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Dong, G., Kim, Y.-I. & Golden, S. S. Simplicity and complexity in the cyanobacterial circadian clock mechanism. Curr. Opin. Gen. Dev. 20, 619–625 (2010).

    Article  CAS  Google Scholar 

  33. Ditty, J. L., Williams, S. B. & Golden, S. S. A cyanobacterial circadian timing mechanism. Annu. Rev. Genet. 37, 513–543 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Dong, G. & Golden, S. S. How a cyanobacterium tells time. Curr. Opin. Microbiol. 11, 541–546 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Tomita, J., Nakajima, M., Kondo, T. & Iwasaki, H. No transcription-translation feedback in circadian rhythm of KaiC phosphorylation. Science 307, 251–254 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Nakajima, M. et al. Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science 308, 414–415 (2005). This work is the first demonstration that the KaiABC system generates self-sustainable oscillations in KaiC phosphorylation in vitro.

    Article  CAS  PubMed  Google Scholar 

  37. Qin, X., Byrne, M., Xu, Y., Mori, T. & Johnson, C. H. Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system. PLoS Biol. 8, e1000394 (2010).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Iwasaki, H., Nishiwaki, T., Kitayama, Y., Nakajima, M. & Kondo, T. KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria. Proc. Natl Acad. Sci. USA 99, 15788–15793 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Xu, Y., Mori, T. & Johnson, C. H. Cyanobacterial circadian clockwork: roles of KaiA, KaiB and the kaiBC promoter in regulating KaiC. EMBO J. 22, 2117–2126 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Mori, T. et al. Circadian clock protein KaiC forms ATP-dependent hexameric rings and binds DNA. Proc. Natl Acad. Sci. USA 99, 17203–17208 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Terauchi, K. et al. ATPase activity of KaiC determines the basic timing for circadian clock of cyanobacteria. Proc. Natl Acad. Sci. USA 104, 16377–16381 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Rust, M. J., Golden, S. S. & O'Shea, E. K. Light-driven changes in energy metabolism directly entrain the cyanobacterial circadian oscillator. Science 331, 220–223 (2011). This study finds that light-induced changes which cause entrainment also induce a change in the ATP/ADP ratio, and that this directly affects KaiC phosphorylation in vitro.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Nishiwaki, T. et al. A sequential program of dual phosphorylation of KaiC as a basis for circadian rhythm in cyanobacteria. EMBO J. 26, 4029–4037 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Rust, M. J., Markson, J. S., Lane, W. S., Fisher, D. S. & O'Shea, E. K. Ordered phosphorylation governs oscillation of a three-protein circadian clock. Science 318, 809–812 (2007). This paper on the KaiABC system illustrates the strength of a combined theoretical and experimental approach.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. van Zon, J. S., Lubensky, D. K., Altena, P. R. H. & ten Wolde, P. R. An allosteric model of circadian KaiC phosphorylation. Proc. Natl Acad. Sci. USA 104, 7420–7425 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Markson, J. S. & O'Shea, E. K. The molecular clockwork of a protein-based circadian oscillator. FEBS Lett. 583, 3938–3947 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Kageyama, H. et al. Cyanobacterial circadian pacemaker: Kai protein complex dynamics in the KaiC phosphorylation cycle in vitro. Mol. Cell 23, 161–171 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Vijayan, V., Zuzow, R. & O'Shea, E. K. Oscillations in supercoiling drive circadian gene expression in cyanobacteria. Proc. Natl Acad. Sci. USA 106, 22564–22568 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ito, H. et al. Cyanobacterial daily life with Kai-based circadian and diurnal genome-wide transcriptional control in Synechococcus elongatus. Proc. Natl Acad. Sci. USA 106, 14168–14173 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mori, T., Binder, B. & Johnson, C. H. Circadian gating of cell division in cyanobacteria growing with average doubling times of less than 24 hours. Proc. Natl Acad. Sci. USA 93, 10183–10188 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Smith, R. M. & Williams, S. B. Circadian rhythms in gene transcription imparted by chromosome compaction in the cyanobacterium Synechococcus elongatus. Proc. Natl Acad. Sci. USA 103, 8564–8569 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Woelfle, M. A., Xu, Y., Qin, X. & Johnson, C. H. Circadian rhythms of superhelical status of DNA in cyanobacteria. Proc. Natl Acad. Sci. USA 104, 18819–18824 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Takai, N. et al. A KaiC-associating SasA–RpaA two-component regulatory system as a major circadian timing mediator in cyanobacteria. Proc. Natl Acad. Sci. USA 103, 12109–12114 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Taniguchi, Y. et al. labA: a novel gene required for negative feedback regulation of the cyanobacterial circadian clock protein KaiC. Genes Dev. 21, 60–70 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Mihalcescu, I., Hsing, W. & Leibler, S. Resilient circadian oscillator revealed in individual cyanobacteria. Nature 430, 81–85 (2004).

    Article  CAS  PubMed  Google Scholar 

  56. Dong, G. et al. Elevated ATPase activity of KaiC applies a circadian checkpoint on cell division in Synechococcus elongatus. Cell 140, 529–539 (2010). This investigation reveals a molecular mechanism for how the circadian oscillator gates cell division.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Schmitz, O., Katayama, M., Williams, S. B., Kondo, T. & Golden, S. S. CikA, a bacteriophytochrome that resets the cyanobacterial circadian clock. Science 289, 765–768 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Ivleva, N. B., Bramlett, M. R., Lindahl, P. A. & Golden, S. S. LdpA: a component of the circadian clock senses redox state of the cell. EMBO J. 24, 1202–1210 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Ivleva, N. B., Gao, T., LiWang, A. C. & Golden, S. S. Quinone sensing by the circadian input kinase of the cyanobacterial circadian clock. Proc. Natl Acad. Sci. USA 103, 17468–17473 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wood, T. L. et al. The KaiA protein of the cyanobacterial circadian oscillator is modulated by a redox-active cofactor. Proc. Natl Acad. Sci. USA 107, 5804–5809 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kutsuna, S., Kondo, T., Aoki, S. & Ishiura, M. A period-extender gene, pex, that extends the period of the circadian clock in the cyanobacterium Synechococcus sp. strain PCC 7942. J. Bacteriol. 180, 2167–2174 (1998).

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Ouyang, Y., Andersson, C. R., Kondo, T., Golden, S. S. & Johnson, C. H. Resonating circadian clocks enhance fitness in cyanobacteria. Proc. Natl Acad. Sci. USA 95, 8660–8664 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ingolia, N. T. & Murray, A. W. The ups and downs of modeling the cell cycle. Curr. Biol. 14, R771–R777 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. O'Neill, J. S. & Reddy, A. B. Circadian clocks in human red blood cells. Nature 469, 498–503 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. O'Neill, J. S. et al. Circadian rhythms persist without transcription in a eukaryote. Nature 469, 554–558 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Cagatay, T., Turcotte, M., Elowitz, M. B., Garcia-Ojalvo, J. & Suel, G. M. Architecture-dependent noise discriminates functionally analogous differentiation circuits. Cell 139, 512–522 (2009). This article uses synthetic constructs to show how two formally identical genetic circuits have very different dynamic properties and respond differently to noise.

    Article  CAS  PubMed  Google Scholar 

  67. Stricker, J. et al. A fast, robust and tunable synthetic gene oscillator. Nature 456, 516–519 (2008). This work employs a synthetic approach to test and compare different design principles of biological oscillators.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bi, E. F. & Lutkenhaus, J. FtsZ ring structure associated with division in Escherichia coli. Nature 354, 161–164 (1991).

    Article  CAS  PubMed  Google Scholar 

  69. Rothfield, L., Taghbalout, A. & Shih, Y. L. Spatial control of bacterial division-site placement. Nature Rev. Microbiol. 3, 959–968 (2005).

    Article  CAS  Google Scholar 

  70. Lutkenhaus, J. Assembly dynamics of the bacterial MinCDE System and spatial regulation of the Z ring. Annu. Rev. Biochem. 76, 539–562 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Adams, D. W. & Errington, J. Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nature Rev. Microbiol. 7, 642–653 (2009).

    Article  CAS  Google Scholar 

  72. Bernhardt, T. G. & de Boer, P. A. J. SlmA, a nucleoid-associated, FtsZ binding protein required for blocking septal ring assembly over chromosomes in E. coli. Mol. Cell 18, 555–564 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. de Boer, P. A. J., Crossley, R. E. & Rothfield, L. I. A division inhibitor and a topological specificity factor coded for by the minicell locus determine proper placement of the division septum in E. coli. Cell 56, 641–649 (1989).

    Article  CAS  PubMed  Google Scholar 

  74. Hu, Z., Mukherjee, A., Pichoff, S. & Lutkenhaus, J. The MinC component of the division site selection system in Escherichia coli interacts with FtsZ to prevent polymerization. Proc. Natl Acad. Sci. USA 96, 14819–14824 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Fu, X., Shih, Y. L., Zhang, Y. & Rothfield, L. I. The MinE ring required for proper placement of the division site is a mobile structure that changes its cellular location during the Escherichia coli division cycle. Proc. Natl Acad. Sci. USA 98, 980–985 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hale, C., Meinhardt, H. & de Boer, P. A. J. Dynamic localization cycle of the cell division regulator MinE in Escherichia coli. EMBO J. 20, 1563–1572 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Raskin, D. M. & de Boer, P. A. J. MinDE-dependent pole-to-pole oscillation of division inhibitor MinC in Escherichia coli. J. Bacteriol. 181, 6419–6424 (1999).

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Raskin, D. M. & de Boer, P. A. J. Rapid pole-to-pole oscillation of a protein required for directing division to the middle of Escherichia coli. Proc. Natl Acad. Sci. USA 96, 4971–4976 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hu, Z. & Lutkenhaus, J. Topological regulation in Escherichia coli involves rapid pole-to-pole oscillation of the division inhibitor MinC under the control of MinD and MinE. Mol. Microbiol. 34, 82–90 (1999).

    Article  CAS  PubMed  Google Scholar 

  80. Meinhardt, H. & de Boer, P. A. J. Pattern formation in Escherichia coli: a model for the pole-to-pole oscillations of Min proteins and the localization of the division site. Proc. Natl Acad. Sci. USA 98, 14202–14207 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Aarsman, M. E. G. et al. Maturation of the Escherichia coli divisome occurs in two steps. Mol. Microbiol. 55, 1631–1645 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. de Boer, P. A., Crossley, R. E., Hand, A. R. & Rothfield, L. I. The MinD protein is a membrane ATPase required for the correct placement of the Escherichia coli division site. EMBO J. 10, 4371–4380 (1991).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Lackner, L. L., Raskin, D. M. & de Boer, P. A. J. ATP-dependent interactions between Escherichia coli Min proteins and the phospholipid membrane in vitro. J. Bacteriol. 185, 735–749 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Suefuji, K., Valluzzi, R. & RayChaudhuri, D. Dynamic assembly of MinD into filament bundles modulated by ATP, phospholipids, and MinE. Proc. Natl Acad. Sci. USA 99, 16776–16781 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Hu, Z., Gogol, E. P. & Lutkenhaus, J. Dynamic assembly of MinD on phospholipid vesicles regulated by ATP and MinE. Proc. Natl Acad. Sci. USA 99, 6761–6766 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Raskin, D. M. & de Boer, P. A. J. The MinE ring: an FtsZ-independent cell structure required for selection of the correct division site in E. coli. Cell 91, 685–694 (1997).

    Article  CAS  PubMed  Google Scholar 

  87. Loose, M., Fischer-Friedrich, E., Ries, J., Kruse, K. & Schwille, P. Spatial regulators for bacterial cell division self-organize into surface waves in vitro. Science 320, 789–792 (2008). This paper describes the reconstitution of the MinD–MinE oscillations on a membrane in vitro and provides evidence that MinD and MinE are the only components required for the oscillations.

    Article  CAS  PubMed  Google Scholar 

  88. Howard, M., Rutenberg, A. D. & de Vet., S. Dynamic compartmentalization of bacteria: accurate division in E. coli. Phys. Rev. Lett. 87, 278102 (2001).

    Article  CAS  PubMed  Google Scholar 

  89. Kruse, K. A dynamic model for determining the middle of Escherichia coli. Biophys. J. 82, 618–627 (2002).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Huang, K. C., Meir, Y. & Wingreen, N. S. Dynamic structures in Escherichia coli: spontaneous formation of MinE rings and MinD polar zones. Proc. Natl Acad. Sci. USA 100, 12724–12728 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kerr, R. A., Levine, H., Sejnowski, T. J. & Rappel, W.-J. Division accuracy in a stochastic model of Min oscillations in Escherichia coli. Proc. Natl Acad. Sci. USA 103, 347–352 (2006).

    Article  CAS  PubMed  Google Scholar 

  92. Huang, K. C., Meir, Y. & Wingreen, N. S. Dynamic structures in Escherichia coli: spontaneous formation of MinE rings and MinD polar zones. Proc. Natl Acad. Sci. USA 100, 12724–12728 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kruse, K. & Jülicher, F. Oscillations in cell biology. Curr. Opin. Cell Biol. 17, 20–26 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. Toro, E. & Shapiro, L. Bacterial chromosome organization and segregation. Cold Spring Harb. Perspect. Biol. 2, a000349 (2010).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Teleman, A. A., Graumann, P. L., Lin, D. C.-H., Grossman, A. D. & Losick, R. Chromosome arrangement within a bacterium. Curr. Biol. 8, 1102–1109 (1998).

    Article  CAS  PubMed  Google Scholar 

  96. Wang, X., Liu, X., Possoz, C. & Sherratt, D. J. The two Escherichia coli chromosome arms locate to separate cell halves. Genes Dev. 20, 1727–1731 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Viollier, P. H. et al. Rapid and sequential movement of individual chromosomal loci to specific subcellular locations during bacterial DNA replication. Proc. Natl Acad. Sci. USA 101, 9257–9262 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Gerdes, K., Howard, M. & Szardenings, F. Pushing and pulling in prokaryotic DNA segregation. Cell 141, 927–942 (2010). This is an excellent review on Par systems, their function in DNA segregation and their similarity to the Min system.

    Article  CAS  PubMed  Google Scholar 

  99. Livny, J., Yamaichi, Y. & Waldor, M. K. Distribution of centromere-like parS sites in bacteria: Insights from comparative genomics. J. Bacteriol. 189, 8693–8703 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Fogel, M. A. & Waldor, M. K. A dynamic, mitotic-like mechanism for bacterial chromosome segregation. Genes Dev. 20, 3269–3282 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  101. Schofield, W. B., Lim, H. C. & Jacobs-Wagner, C. Cell cycle coordination and regulation of bacterial chromosome segregation dynamics by polarly localized proteins. EMBO J. 29, 3068–3081 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. Ptacin, J. L. et al. A spindle-like apparatus guides bacterial chromosome segregation. Nature Cell Biol. 12, 791–798 (2010).

    Article  CAS  PubMed  Google Scholar 

  103. Ebersbach, G. et al. Regular cellular distribution of plasmids by oscillating and filament-forming ParA ATPase of plasmid pB171. Mol. Microbiol. 61, 1428–1442 (2006).

    Article  CAS  PubMed  Google Scholar 

  104. Ringgaard, S., van Zon, J., Howard, M. & Gerdes, K. Movement and equipositioning of plasmids by ParA filament disassembly. Proc. Natl Acad. Sci. USA 106, 19369–19374 (2009). This report provides the first visualization of plasmid oscillations driven by the Par system and combines these observations with theoretical modelling to propose a mechanism for plasmid segregation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ringgaard, S., Ebersbach, G., Borch, J. & Gerdes, K. Regulatory cross-talk in the double par locus of plasmid pB171. J. Biol. Chem. 282, 3134–3145 (2007).

    Article  CAS  PubMed  Google Scholar 

  106. Leonard, T. A., Butler, P. J. & Löwe, J. Bacterial chromosome segregation: structure and DNA binding of the Soj dimer — a conserved biological switch. EMBO J. 24, 270–282 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Ebersbach, G. & Gerdes, K. The double par locus of virulence factor pB171: DNA segregation is correlated with oscillation of ParA. Proc. Natl Acad. Sci. USA 98, 15078–15083 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Ebersbach, G. & Gerdes, K. Bacterial mitosis: partitioning protein ParA oscillates in spiral-shaped structures and positions plasmids at mid-cell. Mol. Microbiol. 52, 385–398 (2004).

    Article  CAS  PubMed  Google Scholar 

  109. Leonardy, S., Bulyha, I. & Søgaard-Andersen, L. Reversing cells and oscillating motility proteins. Mol. Biosyst. 4, 1009–1014 (2008).

    Article  CAS  PubMed  Google Scholar 

  110. Sun, H., Zusman, D. R. & Shi, W. Type IV pilus of Myxococcus xanthus is a motility apparatus controlled by the frz chemosensory system. Curr. Biol. 10, 1143–1146 (2000).

    Article  CAS  PubMed  Google Scholar 

  111. Mignot, T., Merlie, J. P. & Zusman, D. R. Regulated pole-to-pole oscillations of a bacterial gliding motility protein. Science 310, 855–857 (2005). This study is the first to demonstrate how M. xanthus cellular reversals are accompanied by oscillations in protein localization.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  113. Blackhart, B. D. & Zusman, D. R. “Frizzy” genes of Myxococcus xanthus are involved in control of frequency of reversal of gliding motility. Proc. Natl Acad. Sci. USA 82, 8771–8774 (1985).

    Article  Google Scholar 

  114. Bulyha, I. et al. Regulation of the type IV pili molecular machine by dynamic localization of two motor proteins. Mol. Microbiol. 74, 691–706 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  115. Leonardy, S., Freymark, G., Hebener, S., Ellehauge, E. & Søgaard-Andersen, L. Coupling of protein localization and cell movements by a dynamically localized response regulator in Myxococcus xanthus. EMBO J. 26, 4433–4444 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  116. Leonardy, S. et al. Regulation of dynamic polarity switching in bacteria by a Ras-like G-protein and its cognate GAP. EMBO J. 29, 2276–2289 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  117. Zhang, Y., Franco, M., Ducret, A. & Mignot, T. A bacterial Ras-like small GTP-binding protein and its cognate GAP establish a dynamic spatial polarity axis to control directed motility. PLoS Biol. 8, e1000430 (2010). References 116 and 117 are the first demonstrations that a RAS-like G protein, together with its cognate GAP, regulates cell polarity in a bacterium.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  118. Etienne-Manneville, S. Cdc42 – the centre of polarity. J. Cell Sci. 117, 1291–1300 (2004).

    Article  CAS  PubMed  Google Scholar 

  119. Leipe, D. D., Wolf, Y. I., Koonin, E. V. & Aravind, L. Classification and evolution of P-loop GTPases and related ATPases. J. Mol. Biol. 317, 41–72 (2002).

    Article  CAS  PubMed  Google Scholar 

  120. Amir, A., Meshner, S., Beatus, T. & Stavans, J. Damped oscillations in the adaptive response of the iron homeostasis network of E. coli. Mol. Microbiol. 76, 428–436 (2010).

    Article  CAS  PubMed  Google Scholar 

  121. Fischer-Friedrich, E., Meacci, G., Lutkenhaus, J., Chate, H. & Kruse, K. Intra- and intercellular fluctuations in Min-protein dynamics decrease with cell length. Proc. Natl Acad. Sci. USA 107, 6134–6139 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Novak, B. & Tyson, J. J. Design principles of biochemical oscillators. Nature Rev. Mol. Cell Biol. 9, 981–991 (2008). This article gives a thorough overview of the various network motifs that give rise to oscillations, and explains their mathematical description in detail.

    Article  CAS  Google Scholar 

  123. Tyson, J. J., Chen, K. C. & Novak, B. Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr. Opin. Cell Biol. 15, 221–231 (2003).

    Article  CAS  PubMed  Google Scholar 

  124. Elowitz, M. B. & Leibler, S. A synthetic oscillatory network of transcriptional regulators. Nature 403, 335–338 (2000). This report details the first example of a synthetically designed bacterial oscillator.

    Article  CAS  PubMed  Google Scholar 

  125. Gardner, T. S., Cantor, C. R. & Collins, J. J. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 339–342 (2000).

    Article  CAS  PubMed  Google Scholar 

  126. Tsai, T. Y. et al. Robust, tunable biological oscillations from interlinked positive and negative feedback loops. Science 321, 126–129 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  127. Laub, M. T., Chen, S. L., Shapiro, L. & McAdams, H. H. Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle. Proc. Natl Acad. Sci. USA 99, 4632–4637 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Hung., D. Y. & Shapiro, L. A signal transduction protein cues proteolytic events critical to Caulobacter cell cycle progression. Proc. Natl Acad. Sci. USA 99, 13160–13165 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hottes, A. K., Shapiro, L. & McAdams, H. H. DnaA coordinates replication initiation and cell cycle transcription in Caulobacter crescentus. Mol. Microbiol. 58, 1340–1353 (2005).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Work in the authors' laboratories is supported by the Max Planck Society, the German Research Council within the framework of the Graduate School 'Intra- and Intercellular Transport and Communication', and the LOEWE Research Center for Synthetic Microbiology, Marburg, Germany.

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  1. Department of Physics, Philipps-Universität Marburg, Renthof 6, Marburg, 35032, Germany

    Peter Lenz

  2. Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch Str. 10, Marburg, 35043, Germany

    Lotte Søgaard-Andersen

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Glossary

Circadian

Oscillating with a periodicity of 24 h. Derived from the Latin circa, meaning 'around', and diem or dies, meaning 'day', therefore translating to 'approximately 1 day'.

Phosphorelay

An extended version of a two-component system consisting of a histidine protein kinase, a response regulator with a single receiver domain, a phosphotransferase and a response regulator.

Two-component systems

Signalling modules that consist of a pair of proteins. The histidine protein autokinase functions as a sensor, has a conserved kinase domain and autophosphorylates on a conserved histidine residue. The response regulator has a conserved receiver domain that contains a conserved aspartate residue which receives the phosphogroup from the kinase.

Cyclic -di-GMP

A second messenger that is found in bacteria and is generated by enzymes containing a GGDEF domain (named after the conserved residues in the active site).

Hybrid simulations

A type of simulation method involving discrete 'on' and 'off' type dynamics as well as continuous gradual dynamics.

Rate equations

Ordinary differential equations that describe the dynamics of chemical reactions as a function of time. Important applications are the time-dependent changes in protein concentration as a result of synthesis and degradation, and in protein activity as a result of, for example, phosphorylation.

Diurnal

Daily. Derived from the Latin diurnalis.

Kai

A name for a group of proteins. Derived from the Japanese kaiten, meaning a 'cycle' or 'turning of the heavens'.

FtsZ

A bacterial homologue of eukaryotic tubulin that serves as a scaffold for the assembly of the division machinery at the site of cell division in most bacteria.

Nucleoid occlusion

Exclusion of Z ring formation and cell division over the nucleoid. The nucleoid is the region of a bacterial cell that contains the chromosome.

Reaction–diffusion models

Mathematical models that use partial differential equations to describe the motion of molecules by diffusion in space over time. These models include the space-dependent interactions between the involved molecules.

P-loop ATPase

(Phosphate-binding loop ATPase). A member of a superfamily of ATPases and GTPases that contain the conserved P-loop sequence motif. The P-loop is involved in binding of the nucleotide.

Gliding motility

The movement of a rod-shaped bacterium on a surface in the direction of its long axis and in the absence of flagella.

Type IV pili

Dynamic, extracellular protein structures that extend from the cell surface and are periodically retracted. If a pilus is attached to a surface, a retraction event generates a force exceeding 100 pN and pulls a cell forwards.

Focal adhesion complexes

Protein complexes that are distributed regularly along the long axis of a cell and generate mechanical force. During cell movement, the complexes remain stationary with respect to the substrate and move with respect to the cell, from the leading to the lagging cell pole.

Chemosensory system

A variant of a two-component system that uses a methyl-accepting chemotaxis protein (MCP) as a sensor, coupled to a histidine protein kinase by a coupling protein. Often, chemosensory systems show adaptation, with the MCP signalling state being reset by means of methylation and demethylation of the MCP.

G protein

(Guanine-nucleotide-binding protein). A RAS-like G protein is monomeric, consisting of only the GTPase domain and cycle between the inactive, GDP-bound and active, GTP-bound forms. In the GTP-bound form, the G protein interacts with effector proteins to generate an output. The GDP–GTP cycle is regulated by guanine nucleotide exchange factors (GEFs), which stimulate the exchange of GDP for GTP, and GTPase-activating proteins (GAPs), which stimulate GTPase activity.

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Lenz, P., Søgaard-Andersen, L. Temporal and spatial oscillations in bacteria. Nat Rev Microbiol 9, 565–577 (2011). https://doi.org/10.1038/nrmicro2612

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