Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

How to get (a)round: mechanisms controlling growth and division of coccoid bacteria

Nature Reviews Microbiology volume 11, pages 601–614 (2013)Cite this article

Subjects

Key Points

  • Bacteria come in a variety of shapes and sizes, implying that diverse mechanisms exist to coordinate cell growth and division. Our knowledge about the mechanisms controlling growth and division of cocci is mainly derived from studies on the two model organisms Staphylococcus aureus and Streptococcus pneumoniae.

  • During growth, spherical cocci synthesize peptidoglycan only at the division septum, catalysed by one type of cell wall synthesis machinery, whereas ovococci have two modes of cell wall synthesis (septal and peripheral), which are possibly catalysed by two different cell wall synthesis machineries.

  • Control of the S. pneumoniae oval shape is orchestrated by a eukaryotic-type serine/threonine kinase known as StkP. Several cell division proteins are phosphorylated by StkP, which coordinates the shift from peripheral to septal cell wall synthesis.

  • Chromosomal segregation in cocci seems to be driven mainly by passive processes such as DNA replication and transcription, as well as entropy-based demixing of newly replicated DNA. However, active, mitotic-like systems (such as the ParABS and structural maintenance of chromosomes (SMC) complex systems) are often encoded by cocci, so they might also have a role.

  • The spherical species S. aureus divides in three orthogonal planes during three consecutive division cycles. The directionality of chromosome segregation, which is determined through the action of a nucleoid occlusion effector, dictates the placement of the division septum. In S. pneumoniae, ParB, in combination with the SMC complex, seems to facilitate the partitioning of duplicated chromosomes to opposite cell poles.

  • Although the mechanisms involved in regulating the growth and division of cocci are beginning to emerge, future work is required to elucidate the details of the processes involved.

Abstract

Bacteria come in a range of shapes, including round, rod-shaped, curved and spiral cells. This morphological diversity implies that different mechanisms exist to guide proper cell growth, division and chromosome segregation. Although the majority of studies on cell division have focused on rod-shaped cells, the development of new genetic and cell biology tools has provided mechanistic insight into the cell cycles of bacteria with different shapes, allowing us to appreciate the underlying molecular basis for their morphological diversity. In this Review, we discuss recent progress that has advanced our knowledge of the complex mechanisms for chromosome segregation and cell division in bacteria which have, deceptively, the simplest possible shape: the cocci.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cell wall synthesis in cocci and ovococci.
Figure 2: Chromosome segregation in cocci.
Figure 3: Models for the mechanism of division site selection in spherical cocci.

Similar content being viewed by others

References

  1. Angert, E. R. Alternatives to binary fission in bacteria. Nature Rev. Microbiol. 3, 214–224 (2005).

    CAS  Google Scholar 

  2. Young, K. D. Bacterial shape: two-dimensional questions and possibilities. Annu. Rev. Microbiol. 64, 223–240 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Typas, A., Banzhaf, M., Gross, C. A. & Vollmer, W. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nature Rev. Microbiol. 10, 123–136 (2012).

    CAS  Google Scholar 

  4. Eberhardt, A., Wu, L. J., Errington, J., Vollmer, W. & Veening, J. W. Cellular localization of choline-utilization proteins in Streptococcus pneumoniae using novel fluorescent reporter systems. Mol. Microbiol. 74, 395–408 (2009).

    CAS  PubMed  Google Scholar 

  5. Pereira, P. M., Veiga, H., Jorge, A. M. & Pinho, M. G. Fluorescent reporters for studies of cellular localization of proteins in Staphylococcus aureus. Appl. Environ. Microbiol. 76, 4346–4353 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Paprotka, K., Giese, B. & Fraunholz, M. J. Codon-improved fluorescent proteins in investigation of Staphylococcus aureus host pathogen interactions. J. Microbiol. Methods 83, 82–86 (2010).

    CAS  PubMed  Google Scholar 

  7. de Jong, I. G., Beilharz, K., Kuipers, O. P. & Veening, J. W. Live cell imaging of Bacillus subtilis and Streptococcus pneumoniae using automated time-lapse microscopy. J. Vis. Exp. 53, e3145 (2011).

    Google Scholar 

  8. Liew, A. T. F. et al. A simple plasmid-based system that allows rapid generation of tightly controlled gene expression in Staphylococcus aureus. Microbiology 157, 666–676 (2011).

    CAS  PubMed  Google Scholar 

  9. Wheeler, R., Mesnage, S., Boneca, I. G., Hobbs, J. K. & Foster, S. J. Super-resolution microscopy reveals cell wall dynamics and peptidoglycan architecture in ovococcal bacteria. Mol. Microbiol. 82, 1096–1109 (2011).

    CAS  PubMed  Google Scholar 

  10. Kocaoglu, O. et al. Selective penicillin-binding protein imaging probes reveal substructure in bacterial cell division. ACS Chem. Biol. 7, 1746–1753 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ruiz-Masó, J. A. et al. Construction of a plasmid vector based on the pMV158 replicon for cloning and inducible gene expression in Streptococcus pneumoniae. Plasmid 67, 53–59 (2012).

    PubMed  Google Scholar 

  12. Henriques, M. X., Catalão, M. J., Figueiredo, J., Gomes, J. P. & Filipe, S. R. Construction of improved tools for protein localization studies in Streptococcus pneumoniae. PLoS ONE 8, e55049 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Bose, J. L., Fey, P. D. & Bayles, K. W. Genetic tools to enhance the study of gene function and regulation in Staphylococcus aureus. Appl. Environ. Microbiol. 79, 2218–2224 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Brzoska, A. J. & Firth, N. Two-plasmid vector system for independently controlled dual GFP and RFP fusion protein expression in Staphylococcus aureus. Appl. Environ. Microbiol. 79, 3133–3136 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Zapun, A., Vernet, T. & Pinho, M. G. The different shapes of cocci. FEMS Microbiol. Rev. 32, 345–360 (2008).

    CAS  PubMed  Google Scholar 

  16. Lovering, A. L., Safadi, S. S. & Strynadka, N. C. J. Structural perspective of peptidoglycan biosynthesis and assembly. Annu. Rev. Biochem. 81, 451–478 (2012).

    CAS  PubMed  Google Scholar 

  17. Sham, L.-T., Tsui, H.-C. T., Land, A. D., Barendt, S. M. & Winkler, M. E. Recent advances in pneumococcal peptidoglycan biosynthesis suggest new vaccine and antimicrobial targets. Curr. Opin. Microbiol. 15, 194–203 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Pinho, M. G. & Errington, J. Dispersed mode of Staphylococcus aureus cell wall synthesis in the absence of the division machinery. Mol. Microbiol. 50, 871–881 (2003).

    CAS  PubMed  Google Scholar 

  19. Kuru, E. et al. In situ probing of newly synthesized peptidoglycan in live bacteria with fluorescent D-amino acids. Angew. Chem. Int. Ed. Engl. 51, 12519–12523 (2012). This paper describes the development of new tools to visualize the synthesis of peptidoglycan in a wide range of bacteria, including cocci and ovococci.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Scheffers, D. J. & Pinho, M. G. Bacterial cell wall synthesis: new insights from localization studies. Microbiol. Mol. Biol. Rev. 69, 585–607 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Pereira, S. F., Henriques, A. O., Pinho, M. G., de Lencastre, H. & Tomasz, A. Role of PBP1 in cell division of Staphylococcus aureus. J. Bacteriol. 189, 3525–3531 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Atilano, M. L. et al. Teichoic acids are temporal and spatial regulators of peptidoglycan cross-linking in Staphylococcus aureus. Proc. Natl Acad. Sci. USA 107, 18991–18996 (2010). This study provides evidence that wall teichoic acids regulate the localization of PBP4, thus controlling the level of peptidoglycan crosslinking in S. aureus.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Pereira, S. F., Henriques, A. O., Pinho, M. G., de Lencastre, H. & Tomasz, A. Evidence for a dual role of PBP1 in the cell division and cell separation of Staphylococcus aureus. Mol. Microbiol. 72, 895–904 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Pinho, M. G. & Errington, J. Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates. Mol. Microbiol. 55, 799–807 (2005). This is the first paper to show that a PBP can localize to the division septum by substrate recognition.

    CAS  PubMed  Google Scholar 

  25. Wang, L., Khattar, M. K., Donachie, W. D. & Lutkenhaus, J. FtsI and FtsW are localized to the septum in Escherichia coli. J. Bacteriol. 180, 2810–2816 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Mohammadi, T. et al. Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. EMBO J. 30, 1425–1432 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Matias, V. R. & Beveridge, T. J. Cryo-electron microscopy of cell division in Staphylococcus aureus reveals a mid-zone between nascent cross walls. Mol. Microbiol. 64, 195–206 (2007). Using cryo-electron microscopy, this work shows the presence of a so-called mid-zone in the complete division septum, which probably represents a highly fragile region required for efficient cell division in S. aureus.

    CAS  PubMed  Google Scholar 

  28. Seligman, S. J. & Pincus, M. R. A model for the three-dimensional structure of peptidoglycan in staphylococci. J. Theor. Biol. 124, 275–292 (1987).

    CAS  PubMed  Google Scholar 

  29. Higgins, M. L. & Shockman, G. D. Study of cycle of cell wall assembly in Streptococcus faecalis by three-dimensional reconstructions of thin sections of cells. J. Bacteriol. 127, 1346–1358 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Daniel, R. A. & Errington, J. Control of cell morphogenesis in bacteria: two distinct ways to make a rod-shaped cell. Cell 113, 767–776 (2003).

    CAS  PubMed  Google Scholar 

  31. De Pedro, M. A., Quintela, J. C., Holtje, J. V. & Schwarz, H. Murein segregation in Escherichia coli. J. Bacteriol. 179, 2823–2834 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Perez-Nunez, D. et al. A new morphogenesis pathway in bacteria: unbalanced activity of cell wall synthesis machineries leads to coccus-to-rod transition and filamentation in ovococci. Mol. Microbiol. 79, 759–771 (2011). This paper shows that ovoid L. lactis can form rods under particular environmental conditions, such as within biofilms, probably by specific inhibition of a PBP required for septation. This provides evidence for the presence of two distinct cell wall-synthesizing activities in ovococci: septal and peripheral.

    CAS  PubMed  Google Scholar 

  33. Morlot, C., Noirclerc-Savoye, M., Zapun, A., Dideberg, O. & Vernet, T. The D,D-carboxypeptidase PBP3 organizes the division process of Streptococcus pneumoniae. Mol. Microbiol. 51, 1641–1648 (2004). Using immunofluorescence, this investigation provides evidence that the localization of certain S. pneumoniae PBPs at mid-cell depends on substrate availability.

    CAS  PubMed  Google Scholar 

  34. Barendt, S. M., Sham, L. T. & Winkler, M. E. Characterization of mutants deficient in the L,D-carboxypeptidase (DacB) and WalRK (VicRK) regulon, involved in peptidoglycan maturation of Streptococcus pneumoniae serotype 2 strain D39. J. Bacteriol. 193, 2290–2300 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Hasper, H. E. et al. An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II. Science 313, 1636–1637 (2006).

    CAS  PubMed  Google Scholar 

  36. Higgins, M. L. & Shockman, G. D. Model for cell wall growth of Streptococcus faecalis. J. Bacteriol. 101, 643–648 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lleò, M. M., Canepari, P., Fontana, R. & Satta, G. Inhibition of bacterial cell surface extension by various means causes blocking of macromolecular synthesis. Res. Microbiol. 148, 11–20 (1997).

    PubMed  Google Scholar 

  38. Leaver, M. & Errington, J. Roles for MreC and MreD proteins in helical growth of the cylindrical cell wall in Bacillus subtilis. Mol. Microbiol. 57, 1196–1209 (2005).

    CAS  PubMed  Google Scholar 

  39. Land, A. D. & Winkler, M. E. The requirement for pneumococcal MreC and MreD is relieved by inactivation of the gene encoding PBP1a. J. Bacteriol. 193, 4166–4179 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Hempel, A. M. et al. The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces. Proc. Natl Acad. Sci. USA 109, E2371–2379 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Shah, I. M., Laaberki, M. H., Popham, D. L. & Dworkin, J. A eukaryotic-like Ser/Thr kinase signals bacteria to exit dormancy in response to peptidoglycan fragments. Cell 135, 486–496 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Kristich, C. J., Wells, C. L. & Dunny, G. M. A eukaryotic-type Ser/Thr kinase in Enterococcus faecalis mediates antimicrobial resistance and intestinal persistence. Proc. Natl Acad. Sci. USA 104, 3508–3513 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Muñoz-Dorado, J., Inouye, S. & Inouye, M. A gene encoding a protein serine/threonine kinase is required for normal development of M. xanthus, a gram-negative bacterium. Cell 67, 995–1006 (1991).

    PubMed  Google Scholar 

  44. Pereira, S. F., Goss, L. & Dworkin, J. Eukaryote-like serine/threonine kinases and phosphatases in bacteria. Microbiol. Mol. Biol. Rev. 75, 192–212 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Burnside, K. & Rajagopal, L. Regulation of prokaryotic gene expression by eukaryotic-like enzymes. Curr. Opin. Microbiol. 15, 125–131 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Young, T. A., Delagoutte, B., Endrizzi, J. A., Falick, A. M. & Alber, T. Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases. Nature Struct. Biol. 10, 168–174 (2003).

    CAS  PubMed  Google Scholar 

  47. Oliver, A. W., Knapp, S. & Pearl, L. H. Activation segment exchange: a common mechanism of kinase autophosphorylation? Trends Biochem. Sci. 32, 351–356 (2007).

    CAS  PubMed  Google Scholar 

  48. Mir, M. et al. The extracytoplasmic domain of the Mycobacterium tuberculosis Ser/Thr kinase PknB binds specific muropeptides and is required for PknB localization. PLoS Pathog. 7, e1002182 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Fiuza, M. et al. From the characterization of the four serine/threonine protein kinases (PknA/B/G/L) of Corynebacterium glutamicum toward the role of PknA and PknB in cell division. J. Biol. Chem. 283, 18099–18112 (2008).

    CAS  PubMed  Google Scholar 

  50. Beilharz, K. et al. Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP. Proc. Natl Acad. Sci. USA 109, E905–E913 (2012). The first example of the use of single-cell automated fluorescence microscopy in a coccoid bacterium, showing that StkP coordinates peripheral and septal cell wall synthesis in S. pneumoniae.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Echenique, J., Kadioglu, A., Romao, S., Andrew, P. W. & Trombe, M. C. Protein serine/threonine kinase StkP positively controls virulence and competence in Streptococcus pneumoniae. Infect. Immun. 72, 2434–2437 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Nováková, L. et al. Characterization of a eukaryotic type serine/threonine protein kinase and protein phosphatase of Streptococcus pneumoniae and identification of kinase substrates. FEBS J. 272, 1243–1254 (2005).

    PubMed  Google Scholar 

  53. Maestro, B. et al. Recognition of peptidoglycan and β-lactam antibiotics by the extracellular domain of the Ser/Thr protein kinase StkP from Streptococcus pneumoniae. FEBS Lett. 585, 357–363 (2011).

    CAS  PubMed  Google Scholar 

  54. Yeats, C., Finn, R. D. & Bateman, A. The PASTA domain: a β-lactam-binding domain. Trends Biochem. Sci. 27, 438 (2002).

    CAS  PubMed  Google Scholar 

  55. Fleurie, A. et al. Mutational dissection of the S/T-kinase StkP reveals crucial roles in cell division of Streptococcus pneumoniae. Mol. Microbiol. 83, 746–758 (2012). Together with reference 50, this work unambiguously shows a role for StkP in controlling pneumococcal growth and cell division.

    CAS  PubMed  Google Scholar 

  56. Nováková, L. et al. Identification of multiple substrates of the StkP Ser/Thr protein kinase in Streptococcus pneumoniae. J. Bacteriol. 192, 3629–3638 (2010).

    PubMed  PubMed Central  Google Scholar 

  57. Sham, L.-T., Barendt, S. M., Kopecky, K. E. & Winkler, M. E. Essential PcsB putative peptidoglycan hydrolase interacts with the essential FtsXSpn cell division protein in Streptococcus pneumoniae D39. Proc. Natl Acad. Sci. USA 108, E1061–E1069 (2011). This study provides compelling evidence that the conserved FtsEX complex activates the autolysin PcsB and thereby couples peptidoglycan remodelling to cell division in S. pneumoniae.

    PubMed  PubMed Central  Google Scholar 

  58. Giefing-Kröll, C., Jelencsics, K. E., Reipert, S. & Nagy, E. Absence of pneumococcal PcsB is associated with overexpression of LysM domain-containing proteins. Microbiology 157, 1897–1909 (2011).

    PubMed  Google Scholar 

  59. Yang, D. C. et al. An ATP-binding cassette transporter-like complex governs cell-wall hydrolysis at the bacterial cytokinetic ring. Proc. Natl Acad. Sci. USA 108, E1052–E1060 (2011).

    PubMed  PubMed Central  Google Scholar 

  60. Draper, G. C. & Gober, J. W. Bacterial chromosome segregation. Annu. Rev. Microbiol. 56, 567–597 (2002).

    CAS  PubMed  Google Scholar 

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

    PubMed  PubMed Central  Google Scholar 

  62. Reyes-Lamothe, R., Nicolas, E. & Sherratt, D. J. Chromosome replication and segregation in bacteria. Annu. Rev. Genet. 46, 121–143 (2012).

    CAS  PubMed  Google Scholar 

  63. Possoz, C., Junier, I. & Espeli, O. Bacterial chromosome segregation. Front. Biosci. 17, 1020–1034 (2012).

    CAS  Google Scholar 

  64. Wang, X., Llopis, P. M. & Rudner, D. Z. Organization and segregation of bacterial chromosomes. Nature Rev. Genet. 14, 191–203 (2013).

    CAS  PubMed  Google Scholar 

  65. Gerdes, K., Howard, M. & Szardenings, F. Pushing and pulling in prokaryotic DNA segregation. Cell 141, 927–942 (2010).

    CAS  PubMed  Google Scholar 

  66. Nasmyth, K. & Haering, C. H. Cohesin: its roles and mechanisms. Annu. Rev. Genet. 43, 525–558 (2009).

    CAS  PubMed  Google Scholar 

  67. Bürmann, F. et al. An asymmetric SMC–kleisin bridge in prokaryotic condensin. Nature Struct. Mol. Biol. 20, 371–379 (2013).

    Google Scholar 

  68. Sullivan, N. L., Marquis, K. A. & Rudner, D. Z. Recruitment of SMC by ParB–parS organizes the origin region and promotes efficient chromosome segregation. Cell 137, 697–707 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Gruber, S. & Errington, J. Recruitment of condensin to replication origin regions by ParB/Spo0J promotes chromosome segregation in B. subtilis. Cell 137, 685–696 (2009).

    CAS  PubMed  Google Scholar 

  70. Badrinarayanan, A., Reyes-Lamothe, R., Uphoff, S., Leake, M. C. & Sherratt, D. J. In vivo architecture and action of bacterial structural maintenance of chromosome proteins. Science 338, 528–531 (2012).

    CAS  PubMed  Google Scholar 

  71. Minnen, A., Attaiech, L., Thon, M., Gruber, S. & Veening, J. W. SMC is recruited to oriC by ParB and promotes chromosome segregation in Streptococcus pneumoniae. Mol. Microbiol. 81, 676–688 (2011).

    CAS  PubMed  Google Scholar 

  72. Niki, H., Jaffé, A., Imamura, R., Ogura, T. & Hiraga, S. The new gene mukB codes for a 177 kd protein with coiled-coil domains involved in chromosome partitioning of E. coli. EMBO J. 10, 183–193 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Mascarenhas, J., Soppa, J., Strunnikov, A. V. & Graumann, P. L. Cell cycle-dependent localization of two novel prokaryotic chromosome segregation and condensation proteins in Bacillus subtilis that interact with SMC protein. EMBO J. 21, 3108–3118 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Yu, W., Herbert, S., Graumann, P. L. & Gotz, F. Contribution of SMC (structural maintenance of chromosomes) and SpoIIIE to chromosome segregation in staphylococci. J. Bacteriol. 192, 4067–4073 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Bouthier de la Tour, C. et al. The Deinococcus radiodurans SMC protein is dispensable for cell viability yet plays a role in DNA folding. Extremophiles 13, 827–837 (2009).

    CAS  PubMed  Google Scholar 

  76. Mierzejewska, J. & Jagura-Burdzy, G. Prokaryotic ParA–ParB–parS system links bacterial chromosome segregation with the cell cycle. Plasmid 67, 1–14 (2012).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Hui, M. P. et al. ParA2, a Vibrio cholerae chromosome partitioning protein, forms left-handed helical filaments on DNA. Proc. Natl Acad. Sci. USA 107, 4590–4595 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  80. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Pinho, M. G. & Errington, J. A divIVA null mutant of Staphylococcus aureus undergoes normal cell division. FEMS Microbiol. Lett. 240, 145–149 (2004).

    CAS  PubMed  Google Scholar 

  82. Lemon, K. P. & Grossman, A. D. The extrusion-capture model for chromosome partitioning in bacteria. Genes Dev. 15, 2031–2041 (2001).

    CAS  PubMed  Google Scholar 

  83. Migocki, M. D., Lewis, P. J., Wake, R. G. & Harry, E. J. The midcell replication factory in Bacillus subtilis is highly mobile: implications for coordinating chromosome replication with other cell cycle events. Mol. Microbiol. 54, 452–463 (2004).

    CAS  PubMed  Google Scholar 

  84. Reyes-Lamothe, R., Possoz, C., Danilova, O. & Sherratt, D. J. Independent positioning and action of Escherichia coli replisomes in live cells. Cell 133, 90–102 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Nielsen, H. J., Li, Y., Youngren, B., Hansen, F. G. & Austin, S. Progressive segregation of the Escherichia coli chromosome. Mol. Microbiol. 61, 383–393 (2006).

    CAS  PubMed  Google Scholar 

  88. White, M. A., Eykelenboom, J. K., Lopez-Vernaza, M. A., Wilson, E. & Leach, D. R. F. Non-random segregation of sister chromosomes in Escherichia coli. Nature 455, 1248–1250 (2008).

    CAS  PubMed  Google Scholar 

  89. Veiga, H., Jorge, A. M. & Pinho, M. G. Absence of nucleoid occlusion effector Noc impairs formation of orthogonal FtsZ rings during Staphylococcus aureus cell division. Mol. Microbiol. 80, 1366–1380 (2011). This work shows that when Noc is removed from S. aureus , the division sites are frequently misplaced; thus, the authors propose that the axis of chromosome segregation has an important role in division site selection in cocci.

    CAS  PubMed  Google Scholar 

  90. Dworkin, J. & Losick, R. Does RNA polymerase help drive chromosome segregation in bacteria? Proc. Natl Acad. Sci. USA 99, 14089–14094 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Wang, X. & Sherratt, D. J. Independent segregation of the two arms of the Escherichia coli ori region requires neither RNA synthesis nor MreB dynamics. J. Bacteriol. 192, 6143–6153 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Woldringh, C. L. The role of co-transcriptional translation and protein translocation (transertion) in bacterial chromosome segregation. Mol. Microbiol. 45, 17–29 (2002).

    CAS  PubMed  Google Scholar 

  93. Libby, E. A., Roggiani, M. & Goulian, M. Membrane protein expression triggers chromosomal locus repositioning in bacteria. Proc. Natl Acad. Sci. USA 109, 7445–7450 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Jun, S. & Mulder, B. Entropy-driven spatial organization of highly confined polymers: lessons for the bacterial chromosome. Proc. Natl Acad. Sci. USA 103, 12388–12393 (2006). Using computer simulations, this study provides evidence that bacterial chromosomes can segregate spontaneously under certain (topological) conditions by entropy-driven demixing of the DNA–protein polymers.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Jun, S. & Wright, A. Entropy as the driver of chromosome segregation. Nature Rev. Microbiol. 8, 600–607 (2010).

    CAS  Google Scholar 

  96. Le Bourgeois, P. et al. The unconventional Xer recombination machinery of Streptococci/Lactococci. PLoS Genet. 3, e117 (2007).

    PubMed  PubMed Central  Google Scholar 

  97. Nolivos, S. et al. Co-evolution of segregation guide DNA motifs and the FtsK translocase in bacteria: identification of the atypical Lactococcus lactis KOPS motif. Nucleic Acids Res. 40, 5535–5545 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Crozat, E. & Grainge, I. FtsK DNA translocase: the fast motor that knows where it's going. Chembiochem 11, 2232–2243 (2010).

    CAS  PubMed  Google Scholar 

  99. Errington, J., Bath, J. & Wu, L. J. DNA transport in bacteria. Nature Rev. Mol. Cell Biol. 2, 538–545 (2001).

    CAS  Google Scholar 

  100. Trueba, F. J. On the precision and accuracy achieved by Escherichia coli cells at fission about their middle. Arch. Microbiol. 131, 55–59 (1982).

    CAS  PubMed  Google Scholar 

  101. Migocki, M. D., Freeman, M. K., Wake, R. G. & Harry, E. J. The Min system is not required for precise placement of the midcell Z ring in Bacillus subtilis. EMBO Rep. 3, 1163–1167 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Zaritsky, A. & Woldringh, C. L. Localizing cell division in spherical Escherichia coli by nucleoid occlusion. FEMS Microbiol. Lett. 226, 209–214 (2003).

    CAS  PubMed  Google Scholar 

  103. Pas, E., Einav, M., Woldringh, C. L. & Zaritsky, A. Perpendicular planes of FtsZ arcs in spheroidal Escherichia coli cells. Biochimie 83, 121–124 (2001).

    CAS  PubMed  Google Scholar 

  104. Corbin, B. D., Yu, X. C. & Margolin, W. Exploring intracellular space: function of the Min system in round-shaped Escherichia coli. EMBO J. 21, 1998–2008 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Wu, L. J. & Errington, J. Nucleoid occlusion and bacterial cell division. Nature Rev. Microbiol. 10, 8–12 (2012).

    CAS  Google Scholar 

  106. Koch, A. L. & Doyle, R. J. Attachment of the chromosome to the cell poles: the strategy for the growth of bacteria in two and three dimensions. J. Theor. Biol. 199, 213–221 (1999).

    CAS  PubMed  Google Scholar 

  107. Yamada, S. et al. An autolysin ring associated with cell separation of Staphylococcus aureus. J. Bacteriol. 178, 1565–1571 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Turner, R. D. et al. Peptidoglycan architecture can specify division planes in Staphylococcus aureus. Nature Commun. 1, 1–9 (2010). Using atomic force microscopy on purified cell walls from S. aureus , this study demonstrates that cells build a large belt of peptidoglycan at mid-cell and this belt is retained there during growth and division, and thus might be used as an 'epigenetic' landmark to select future division sites.

    Google Scholar 

  109. Ramirez-Arcos, S. et al. Deletion of the cell-division inhibitor MinC results in lysis of Neisseria gonorrhoeae. Microbiology 147, 225–237 (2001).

    CAS  PubMed  Google Scholar 

  110. Szeto, J. et al. Gonococcal MinD affects cell division in Neisseria gonorrhoeae and Escherichia coli and exhibits a novel self-interaction. J. Bacteriol. 183, 6253–6264 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Ramirez-Arcos, S., Szeto, J., Dillon, J.-A. R. & Margolin, W. Conservation of dynamic localization among MinD and MinE orthologues: oscillation of Neisseria gonorrhoeae proteins in Escherichia coli. Mol. Microbiol. 46, 493–504 (2002).

    CAS  PubMed  Google Scholar 

  112. Ramirez-Arcos, S., Liao, M., Marthaler, S., Rigden, M. & Dillon, J.-A. R. Enterococcus faecalis divIVA: an essential gene involved in cell division, cell growth and chromosome segregation. Microbiology 151, 1381–1393 (2005).

    CAS  PubMed  Google Scholar 

  113. Fadda, D. et al. Streptococcus pneumoniae DivIVA: localization and interactions in a MinCD-free context. J. Bacteriol. 189, 1288–1298 (2007). This work shows that DivIVA in S. pneumoniae is involved in the formation and maturation of the future cell poles, and demonstrates an interaction between DivIVA and ParB, hinting at a possible role for DivIVA as a chromosome-tethering factor required for efficient chromosome segregation.

    CAS  PubMed  Google Scholar 

  114. Flärdh, K. Essential role of DivIVA in polar growth and morphogenesis in Streptomyces coelicolor A3(2). Mol. Microbiol. 49, 1523–1536 (2003).

    PubMed  Google Scholar 

  115. Donovan, C., Sieger, B., Krämer, R. & Bramkamp, M. A synthetic Escherichia coli system identifies a conserved origin tethering factor in Actinobacteria. Mol. Microbiol. 84, 105–116 (2012).

    CAS  PubMed  Google Scholar 

  116. Levin, P. A., Kurtser, I. G. & Grossman, A. D. Identification and characterization of a negative regulator of FtsZ ring formation in Bacillus subtilis. Proc. Natl Acad. Sci. USA 96, 9642–9647 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Wu, L. J. & Errington, J. Coordination of cell division and chromosome segregation by a nucleoid occlusion protein in Bacillus subtilis. Cell 117, 915–925 (2004).

    CAS  PubMed  Google Scholar 

  118. Claessen, D. et al. Control of the cell elongation-division cycle by shuttling of PBP1 protein in Bacillus subtilis. Mol. Microbiol. 68, 1029–1046 (2008).

    CAS  PubMed  Google Scholar 

  119. Thanassi, J. A., Hartman-Neumann, S. L., Dougherty, T. J., Dougherty, B. A. & Pucci, M. J. Identification of 113 conserved essential genes using a high-throughput gene disruption system in Streptococcus pneumoniae. Nucleic Acids Res. 30, 3152–3162 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Chaudhuri, R. R. et al. Comprehensive identification of essential Staphylococcus aureus genes using Transposon-Mediated Differential Hybridisation (TMDH). BMC Genomics 10, 291 (2009).

    PubMed  PubMed Central  Google Scholar 

  121. Steele, V. R., Bottomley, A. L., Garcia-Lara, J., Kasturiarachchi, J. & Foster, S. J. Multiple essential roles for EzrA in cell division of Staphylococcus aureus. Mol. Microbiol. 80, 542–555 (2011).

    CAS  PubMed  Google Scholar 

  122. Jorge, A. M., Hoiczyk, E., Gomes, J. P. & Pinho, M. G. EzrA contributes to the regulation of cell size in Staphylococcus aureus. PLoS ONE 6, e27542 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Stackebrandt, E. & Woese, C. R. A phylogenetic dissection of the family micrococcaceae. Curr. Microbiol. 2, 317–322 (1979).

    CAS  Google Scholar 

  124. Woese, C. R., Blanz, P., Hespell, R. B. & Hahn, C. M. Phylogenetic relationships among various helical bacteria. Curr. Microbiol. 7, 119–124 (1982).

    CAS  Google Scholar 

  125. Siefert, J. L. & Fox, G. E. Phylogenetic mapping of bacterial morphology. Microbiology 144, 2803–2808 (1998).

    CAS  Google Scholar 

  126. Henriques, A. O., Glaser, P., Piggot, P. J. & Moran, C. P. Control of cell shape and elongation by the rodA gene in Bacillus subtilis. Mol. Microbiol. 28, 235–247 (1998).

    CAS  PubMed  Google Scholar 

  127. Jones, L. J., Carballido-Lopez, R. & Errington, J. Control of cell shape in bacteria: helical, actin-like filaments in Bacillus subtilis. Cell 104, 913–922 (2001).

    CAS  PubMed  Google Scholar 

  128. Aldea, M., Hernandez-Chico, C., de la Campa, A. G., Kushner, S. R. & Vicente, M. Identification, cloning, and expression of bolA, an ftsZ-dependent morphogene of Escherichia coli. J. Bacteriol. 170, 5169–5176 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Gupta, R. S. The phylogeny of proteobacteria: relationships to other eubacterial phyla and eukaryotes. FEMS Microbiol. Rev. 24, 367–402 (2000).

    CAS  PubMed  Google Scholar 

  130. Tamames, J., González-Moreno, M., Mingorance, J., Valencia, A. & Vicente, M. Bringing gene order into bacterial shape. Trends Genet. 17, 124–126 (2001).

    CAS  PubMed  Google Scholar 

  131. Goffin, C. & Ghuysen, J. M. Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol. Mol. Biol. Rev. 62, 1079–1093 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Ghuysen, J. M. Serine β-lactamases and penicillin-binding proteins. Annu. Rev. Microbiol. 45, 37–67 (1991).

    CAS  PubMed  Google Scholar 

  133. Curtis, N. A. C., Hayes, M. V., Wyke, A. W. & Ward, J. B. A mutant of Staphylococcus aureus H lacking penicillin-binding protein 4 and transpeptidase activity in vitro. FEMS Microbiol. Lett. 9, 263–266 (1980).

    CAS  Google Scholar 

  134. Scheffers, D. J., de Wit, J. G., den Blaauwen, T. & Driessen, A. J. M. GTP hydrolysis of cell division protein FtsZ: evidence that the active site is formed by the association of monomers. Biochemistry 41, 521–529 (2002).

    CAS  PubMed  Google Scholar 

  135. Osawa, M., Anderson, D. E. & Erickson, H. P. Reconstitution of contractile FtsZ rings in liposomes. Science 320, 792–794 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Adams, D. W. & Errington, J. Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nature Rev. Microbiol. 7, 642–563 (2009).

    CAS  Google Scholar 

  137. Egan, A. J. F. & Vollmer, W. The physiology of bacterial cell division. Ann. NY Acad. Sci. 1277, 8–28 (2013).

    CAS  PubMed  Google Scholar 

  138. Dominguez-Escobar, J. et al. Processive movement of MreB-associated cell wall biosynthetic complexes in bacteria. Science 333, 225–228 (2011).

    CAS  PubMed  Google Scholar 

  139. Garner, E. C. et al. Coupled, circumferential motions of the cell wall synthesis machinery and MreB filaments in B. subtilis. Science 333, 222–225 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. van Teeffelen, S. et al. The bacterial actin MreB rotates, and rotation depends on cell-wall assembly. Proc. Natl Acad. Sci. USA 108, 15822–15827 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Lutkenhaus, J. Assembly dynamics of the bacterial MinCDE system and spatial regulation of the Z ring. Annu. Rev. Biochem. 76, 14 (2007).

    Google Scholar 

  142. Bramkamp, M. & van Baarle, S. Division site selection in rod-shaped bacteria. Curr. Opin. Microbiol. 12, 683–688 (2009).

    CAS  PubMed  Google Scholar 

  143. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Edwards, D. H. & Errington, J. The Bacillus subtilis DivIVA protein targets to the division septum and controls the site specificity of cell division. Mol. Microbiol. 24, 905–915 (1997).

    CAS  PubMed  Google Scholar 

  145. Bramkamp, M. et al. A novel component of the division-site selection system of Bacillus subtilis and a new mode of action for the division inhibitor MinCD. Mol. Microbiol. 70, 1556–1569 (2008).

    CAS  PubMed  Google Scholar 

  146. Eswaramoorthy, P. et al. Cellular architecture mediates DivIVA ultrastructure and regulates min activity in Bacillus subtilis. mBio 2, e00257-11 (2011).

    PubMed  PubMed Central  Google Scholar 

  147. Lenarcic, R. et al. Localisation of DivIVA by targeting to negatively curved membranes. EMBO J. 28, 2272–2282 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Ramamurthi, K. S. & Losick, R. Negative membrane curvature as a cue for subcellular localization of a bacterial protein. Proc. Natl Acad. Sci. USA 106, 13541–13545 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Mulder, E. & Woldringh, C. L. Actively replicating nucleoids influence positioning of division sites in Escherichia coli filaments forming cells lacking DNA. J. Bacteriol. 171, 4303–4314 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Woldringh, C. L., Mulder, E., Huls, P. G. & Vischer, N. Toporegulation of bacterial division according to the nucleoid occlusion model. Res. Microbiol. 142, 309–320 (1991).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Wu, L. J. et al. Noc protein binds to specific DNA sequences to coordinate cell division with chromosome segregation. EMBO J. 28, 1940–1952 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Cho, H., McManus, H. R., Dove, S. L. & Bernhardt, T. G. Nucleoid occlusion factor SlmA is a DNA-activated FtsZ polymerization antagonist. Proc. Natl Acad. Sci. USA 108, 3773–3778 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Tonthat, N. K. et al. Molecular mechanism by which the nucleoid occlusion factor, SlmA, keeps cytokinesis in check. EMBO J. 30, 154–164 (2011).

    CAS  PubMed  Google Scholar 

  155. Bendezu, F. O., Hale, C. A., Bernhardt, T. G. & de Boer, P. A. RodZ (YfgA) is required for proper assembly of the MreB actin cytoskeleton and cell shape in E. coli. EMBO J. 28, 193–204 (2009).

    CAS  PubMed  Google Scholar 

  156. Moriya, S., Rashid, R. A., Rodrigues, C. D. & Harry, E. J. Influence of the nucleoid and the early stages of DNA replication on positioning the division site in Bacillus subtilis. Mol. Microbiol. 76, 634–647 (2010).

    CAS  PubMed  Google Scholar 

  157. Veiga, H. & Pinho, M. G. Bacterial cell division: what it takes to divide a prokaryotic cell. Canal BQ 9, 18–26 (2012).

    Google Scholar 

  158. Huang, K. C. & Wingreen, N. S. Min-protein oscillations in round bacteria. Phys. Biol. 1, 229–235 (2004). This paper describes a numerical model which predicts that Min protein oscillations occur in spherical cells.

    CAS  PubMed  Google Scholar 

  159. Lechner, M. et al. Proteinortho: detection of (co-)orthologs in large-scale analysis. BMC Bioinformatics 12, 124 (2011).

    PubMed  PubMed Central  Google Scholar 

  160. White, C. L., Kitich, A. & Gober, J. W. Positioning cell wall synthetic complexes by the bacterial morphogenetic proteins MreB and MreD. Mol. Microbiol. 76, 616–633 (2010).

    CAS  PubMed  Google Scholar 

  161. Dworkin, M. & Falkow, S. The Prokaryotes. Vol. 4: Bacteria: Firmicutes, Cyanobacteria. (Springer, 2006).

    Google Scholar 

Download references

Acknowledgements

The authors thank S. Filipe, D.-J. Scheffers and L. Wu for helpful comments on the manuscript, and A. de Jong for assistance with bioinformatics. Work in the laboratory of M.G.P. is supported by the European Research Council (grant ERC-2012-StG-310987) and by the Fundação para a Ciência e Tecnologia (grant PTDC/BIA-MIC/099151/2008). M.K. is supported by a Long-Term Fellowship from the Federation of European Biochemical Societies (FEBS). Work in the laboratory of J.-W.V. is supported by a VENI fellowship and a Sysmo2 grant from the Netherlands Organisation for Scientific Research, Earth and Life Sciences (NWO-ALW). The authors apologize to colleagues whose work is not cited fully owing to space restrictions.

Author information

Authors and Affiliations

  1. Laboratory of Bacterial Cell Biology, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Avenida da República, Oeiras, 2780–157, Portugal

    Mariana G. Pinho

  2. Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Nijenborgh 7, Groningen, 9747 AG, The Netherlands

    Morten Kjos & Jan-Willem Veening

Authors
  1. Mariana G. Pinho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Morten Kjos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jan-Willem Veening
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mariana G. Pinho or Jan-Willem Veening.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Glossary

Divisome

A large complex of proteins that assembles at the division site and drives cytokinesis.

Wall teichoic acid

An anionic glycopolymer that is bound to the peptidoglycan of Gram-positive bacteria.

Equatorial rings

Annular rings of peptidoglycan that are present in the middle of the cell during cell division in some ovococci. These rings mark the future division sites in new daughter cells.

MreB

An actin-like cytoskeletal protein that assembles in short discrete patches which move processively along the cell periphery, perpendicular to the long axis of the cell, powered by peptidoglycan synthesis. MreB might spatially organize the proteins that are required for cell wall synthesis.

FtsZ

A tubulin-like protein with GTPase activity and the first protein found to be recruited to the future division site, where it polymerizes to form the Z ring.

Structured-illumination microscopy

A technique that uses spatially structured illumination and increases the spatial resolution of wide-field fluorescence microscopy to beyond the classical limit.

Septal disc

A structure that forms in the middle of the mother cell during cell division, by invagination of the cell membrane and ingrowth of the cell wall.

Hanks-type kinases

Serine/threonine kinases with the so-called Hanks fold. The catalytic residues and overall structure of this fold are highly conserved, and it is found, for example, in the kinase domain of eukaryotic cyclic AMP-dependent protein kinase A and Streptococcus pneumoniae StkP.

Mitotic spindle

A microtubule-based eukaryotic subcellular structure that pulls sister chromatids apart during cell division.

Structural maintenance of chromosomes complex

A protein complex with a putative role in organizing the origin regions in bacteria during replication. The functional homologue of this complex in Escherichia coli and related alphaproteobacteria is called the MukBEF complex.

Transertion

The coupling of transcription–translation and protein insertion into the membrane. This results in localization of the DNA–RNA polymerase–RNA–ribosome–peptide complex at the membrane.

Decatenation

The resolution of interlinked circular chromosomes through the breaking and re-ligating of DNA bonds by topoisomerase.

Entropic forces

Conformational entropy generated by processes such as DNA supercoiling and compaction. Entropic forces are proposed to be major guiding forces for the segregation of bacterial chromosomes, leading to the spontaneous demixing of daughter strands.

Epigenetic information

Cues or signals that result in changes in gene expression or phenotypes independently of changes in DNA sequence.

dcw cluster

A region in bacterial chromosomes that encodes various genes involved in cell division and cell wall synthesis

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pinho, M., Kjos, M. & Veening, JW. How to get (a)round: mechanisms controlling growth and division of coccoid bacteria. Nat Rev Microbiol 11, 601–614 (2013). https://doi.org/10.1038/nrmicro3088

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro3088

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology