Binary Fission in Bacteria


Given a suitable environment, most free‐living prokaryotic cells (including bacteria) will grow continually until, on reaching a critical size, they divide into two equal‐sized parts in a process called binary fission. To be successful, this process requires the accurate duplication and partition of the chromosomes, and subsequent splitting of the cytoplasm precisely at the cell midpoint. The latter process, known as cytokinesis, often uses a large transmembrane protein machine that includes homologues of actin and tubulin as well as enzymes that synthesise and degrade specific portions of the cell wall. The placement of this machine is often regulated by negatively acting morphogen gradients. Once assembled, numerous accessory proteins respond to various inputs to regulate how and when the machine constricts and cells physically separate.

Key Concepts:

  • The timing of chromosome duplication in bacteria responds to cell growth rate and initiates at a specific location only once per cell cycle.

  • Bacterial chromosomes are organised and condensed by DNA‐binding proteins, some of which are conserved from bacteria to humans.

  • Bacterial cells use homologues of eukaryotic cytoskeletal proteins actin and tubulin to organise their growth and division.

  • Morphogen gradients of negative spatial regulators help to position the cytokinetic ring in many bacteria.

  • Recent advances in synthetic biology of bacterial cytokinesis are increasing our understanding of key components.

Keywords: Escherichia coli; prokaryotes; cell cycle; cell division; cytokinesis; DNA; chromosome replication; fts genes

Figure 1.

Basic growth modes of six representative bacterial species that undergo binary fission: Three species that contain MreB (a) and three species that lack MreB (b) are shown, with an arrow representing the transition between a newly divided cell and a cell immediately before binary fission. The general modes of growth are summarised below for each. For each stage, areas of the cell probably not engaged in significant peptidoglycan synthesis are outlined in blue; areas actively synthesising PG are outlined in other colours. Areas of MreB‐dependent wall growth are shown in red or magenta; the magenta in C. crescentus indicates a slower growth relative to the red, resulting in crescent‐shaped cells. Areas of FtsZ‐dependent wall growth are shown in green. Solid green outlines indicate septal wall synthesis, and green dots indicate probable locations of active FtsZ‐directed sidewall synthesis. Areas of DivIVA‐dependent wall growth are shown in orange. Reprinted from Margolin () with permission from Elsevier. © Elsevier.

Figure 2.

Change in size and chromosome content of an E. coli cell with growth rate. Imagine a newborn cell of minimal size (0.5 initiation mass (Mi)) with a single unreplicated chromosome, as might be found in a stationary‐phase culture (generation time, τ). The diagram illustrates what would happen if such a cell were placed in a relatively poor medium, in which the cell can double its mass every hour (mass doubling time τ=60 min), or a very rich medium in which the cell can double in mass every 20 min (τ=20 min). Cells increase in mass exponentially. Chromosomes are represented as circles. In poor medium, growth begins immediately but chromosome replication does not start until cell mass reaches Mi (after 60 min). Replication takes a further 40 min (C period). Septation takes a further 20 min (D period) and the cell divides into two equal sister cells, each with one chromosome, at 120 min. The size of each newborn sister cell is now equal to Mi and chromosome replication can begin again. Although the cells continue to grow at this rate (τ=60 min) this process will repeat every 60 min, with newborn cells always being equal to 1 Mi. In the rich medium, the cell reaches Mi after 20 min and chromosome replication begins. This round of replication also takes 40 min, followed by 20 min to complete the septum and divide; however, because the cell is growing so quickly it will have reached a mass equivalent to 8 Mi: each sister cell will be 4 Mi. The faster they grow, the larger they will be. Each time Mi doubles, a new round of replication begins, even though the previous one has not yet been completed. After the first 80 min in the rich medium, cells therefore initiate chromosome replication and divide every 20 min, but each newborn cell will have two half‐replicated copies of the chromosome. Therefore the faster the cells grow, the more chromosome copies they will have.

Figure 3.

DNA replication cycle of E. coli. Successive stages (10‐min intervals) in cell growth at 37 °C in a synthetic medium, which allows cells to double in mass every 80 min. In such a slow‐growing cell it is possible to see successive stages separated in time, rather than overlapping as they do during rapid growth (in media allowing generation times of less than 60 min at 37 °C). The DNA is shown as a thick open circle with the chromosomal replication origin, oriC (o) and terminus (t) on opposite sides. When the cell reaches a critical mass (initiation mass (Mi)) chromosome replication begins. The initial events in replication are the separation of the complementary DNA strands at oriC, carried out by the ATP‐bound form of DnaA protein (blue spheres), followed by the entry of the proteins of the replication complex or replisome (red spheres) and synthesis of new complementary DNA strands (thin ovals). DNA synthesis is confined to a location near the cell centre, where the old chromosome is fed progressively into the replication complex and the newly replicated parts are extruded. MukB proteins (dark blue spheres) help to organise and condense the newly synthesised DNA strands. Premature reinitiation of replication at the two newly completed copies of oriC is prevented by SeqA protein (green sphere). Soon after replication begins, the two new copies of the oriC region rapidly move to opposite ends of the cell; unreplicated DNA (thick circle) remains near the cell centre. Completion of chromosome replication and subsequent packaging of the two sister chromosomes into the two new cells requires a further series of events. The two replisomes meet and complete replication in the ter region, but, because a circular double helix has been replicated, the two completed circles of DNA are interlinked (concatenated) at the completion of replication. Decatenation, the unlinking of the circles, requires double‐strand breakage and rejoining and is carried out by a specific topoisomerase, Topo IV (the product of the parC and parE genes, orange triangles). A further process is required in some cells: if recombination has taken place between replicated parts of the chromosome, the final result of complete replication is a single double‐sized circle, a chromosome dimer. Resolution of such dimers into two sister monomers takes place by site‐specific recombination at a special site (dif) located in the ter region. Resolution requires specific resolvases (XerC and XerD proteins) and also the FtsK protein, which is also located at the cell centre as part of the cytokinetic ring of proteins (blue rectangles). This dimer resolution leads to the partitioning of chromosomes to each daughter cell by a mechanism that is yet unsolved.

Figure 4.

The E. coli cytokinesis machine. At the left are successive stages of cytokinesis, showing the localisation of the nucleoid (red oval) and replisome (small dot) as well as the Z ring. The Z ring initially localises to the midcell between the partitioned daughter nucleoids as a result of the action of negative morphogen gradients mediated by SlmA and the Min proteins (see Figure ). The proto‐ring, containing FtsZ, FtsA and ZipA, is shown as a white ring. This proto‐ring recruits the remainder of the divisome proteins and is now poised to constrict (magenta ring). Ring constriction is then triggered by unknown factors, followed by controlled invagination of the inner and outer membranes as well as building of septal peptidoglycan and breaking of other cell wall bonds by hydrolases until the membranes fuse, split, and cells physically separate. The divisome disassembles, and the process repeats. At the right are fluorescence micrographs of E. coli cells synthesising an FtsZ–GFP fusion, allowing direct observation of the Z ring during cytokinesis. At the upper right, three cells lie parallel, with their outlines highlighted. Only the middle cell will divide during the time course. At the lower right is a 3‐D image reconstruction of an E. coli cell with a fluorescent Z ring at an early stage.

Figure 5.

Themes and variations on how bacteria find their middles for binary fission. Three model bacteria are shown, along with their morphogenetic Z ring centring systems. In C. crescentus, the ATPase MipZ (orange dots) binds near oriC (green circle) and inhibits local FtsZ assembly mostly at the oriC end of the cell (where a structure called the stalk is located) but forms a gradient that spreads down the cell. The result is that FtsZ forms a focus at the opposite end of the cell (purple dots) where the flagellum is located, at the lowest concentration of MipZ. Upon oriC duplication and chromosome segregation, the new oriC moves to the flagellum end of the cell, and MipZ follows, disrupting the FtsZ focus and forming a bipolar gradient of MipZ. Consequently, FtsZ is forced to assemble at the cell centre, again at the lowest concentration of the MipZ inhibitor. This mechanism nicely couples the DNA replication cycle with Z ring centring. In E. coli, the oscillating Min proteins (orange gradient) inhibit the Z ring assembly at the cell poles; FtsZ is shown attempting to assemble into polymeric structures at the cell pole but is chased to the opposite pole. Nucleoid occlusion (teal) keeps FtsZ from forming a ring until late in the replication cycle, where the Z ring forms at the zone of lowest inhibition. B. subtilis is similar to E. coli except that the Min proteins are anchored to the cell poles by DivIVA and MinJ and thus form a static gradient that keeps FtsZ at the lowest concentration of MinCD at the midcell. Reprinted from Margolin () with permission from Elsevier. © Elsevier.



Adams DW and Errington J (2009) Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nature Reviews Microbiology 7: 642–653.

Alexeeva S, Gadella TW Jr, Verheul J et al. (2010) Direct interactions of early and late assembling division proteins in Escherichia coli cells resolved by FRET. Molecular Microbiology 77: 384–398.

Badrinarayanan A, Reyes‐Lamothe R, Uphoff S et al. (2012) In vivo architecture and action of bacterial structural maintenance of chromosome proteins. Science 338: 528–531.

Boye E, Stokke T, Kleckner N et al. (1996) Coordinating DNA replication initiation with cell growth: differential roles for DnaA and SeqA proteins. Proceedings of the National Academy of Sciences of the USA 93: 12206–12211.

Bramkamp M, Emmins R, Weston L et al. (2008) A novel component of the division‐site selection system of Bacillus subtilis and a new mode of action for the division inhibitor MinCD. Molecular Microbiology 70: 1556–1569.

Cabre EJ, Sanchez‐Gorostiaga A, Carrara P et al. (2013) Bacterial division proteins FtsZ and ZipA induce vesicle shrinkage and cell membrane invagination. Journal of Biological Chemistry 288: 26625–26634.

Chien AC, Zareh SK, Wang YM et al. (2012) Changes in the oligomerization potential of the division inhibitor UgtP co‐ordinate Bacillus subtilis cell size with nutrient availability. Molecular Microbiology 86: 594–610.

Cho H and Bernhardt TG (2013) Identification of the SlmA active site responsible for blocking bacterial cytokinetic ring assembly over the chromosome. PLoS Genetics 9: e1003304.

Ding Z, Zhao Z, Jakubowski SJ et al. (2002) A novel cytology‐based, two‐hybrid screen for bacteria applied to protein–protein interaction studies of a type IV secretion system. Journal of Bacteriology 184: 5572–5582.

Di Ventura B, Knecht B, Andreas H et al. (2013) Chromosome segregation by the Escherichia coli Min system. Molecular Systems Biology 9: 686.

Dominguez‐Escobar J, Chastanet A, Crevenna AH et al. (2011) Processive movement of MreB‐associated cell wall biosynthetic complexes in bacteria. Science 333: 225–228.

Donachie WD and Begg KJ (1996) “Division potential” in Escherichia coli. Journal of Bacteriology 178: 5971–5976.

Donachie WD, Begg KJ and Vicente M (1976) Cell length, cell growth and cell division. Nature 264: 328–333.

Donachie WD and Blakely GW (2003) Coupling the initiation of chromosome replication to cell size in Escherichia coli. Current Opinion in Microbiology 6: 146–150.

Dupaigne P, Tonthat NK, Espeli O et al. (2012) Molecular basis for a protein‐mediated DNA‐bridging mechanism that functions in condensation of the E. coli chromosome. Molecular Cell 48: 560–571.

Errington J (2013) L‐form bacteria, cell walls and the origins of life. Open Biology 3: 120143.

Fenton AK and Gerdes K (2013) Direct interaction of FtsZ and MreB is required for septum synthesis and cell division in Escherichia coli. EMBO Journal 32: 1953–1965.

Fisher JK, Bourniquel A, Witz G et al. (2013) Four‐dimensional imaging of E. coli nucleoid organization and dynamics in living cells. Cell 153: 882–895.

Fu G, Huang T, Buss J et al. (2010) In vivo structure of the E. coli FtsZ‐ring revealed by photoactivated localization microscopy (PALM). PLoS One 5: e12682.

Garner EC, Bernard R, Wang W et al. (2011) Coupled, circumferential motions of the cell wall synthesis machinery and MreB filaments in B. subtilis. Science 333: 222–225.

Gerding MA, Ogata Y, Pecora ND et al. (2007) The trans‐envelope Tol‐Pal complex is part of the cell division machinery and required for proper outer‐membrane invagination during cell constriction in E. coli. Molecular Microbiology 63: 1008–1025.

Hayama R and Marians KJ (2010) Physical and functional interaction between the condensin MukB and the decatenase topoisomerase IV in Escherichia coli. Proceedings of the National Academy of Sciences of the USA 107: 18826–18831.

Hill NS, Buske PJ, Shi Y et al. (2013) A moonlighting enzyme links Escherichia coli cell size with central metabolism. PLoS Genetics 9: e1003663.

Karimova G, Dautin N and Ladant D (2005) Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two‐hybrid analysis. Journal of Bacteriology 187: 2233–2243.

Kasho K and Katayama T (2013) DnaA binding locus datA promotes DnaA–ATP hydrolysis to enable cell cycle‐coordinated replication initiation. Proceedings of the National Academy of Sciences of the USA 110: 936–941.

Katayama T, Ozaki S, Keyamura K et al. (2010) Regulation of the replication cycle: conserved and diverse regulatory systems for DnaA and oriC. Nature Reviews Microbiology 8: 163–170.

Kiekebusch D, Michie KA, Essen LO et al. (2012) Localized dimerization and nucleoid binding drive gradient formation by the bacterial cell division inhibitor MipZ. Molecular Cell 46: 245–259.

Leaver M, Dominguez‐Cuevas P, Coxhead JM et al. (2009) Life without a wall or division machine in Bacillus subtilis. Nature 457: 849–853.

Löwe J and Amos LA (1998) Crystal structure of the bacterial cell‐division protein FtsZ. Nature 391: 203–206.

Lutkenhaus J, Pichoff S and Du S (2012) Bacterial cytokinesis: from Z ring to divisome. Cytoskeleton (Hoboken) 69: 778–790.

Maggi S, Massidda O, Luzi G et al. (2008) Division protein interaction web: identification of a phylogenetically conserved common interactome between Streptococcus pneumoniae and Escherichia coli. Microbiology 154: 3042–3052.

Margolin W (2009a) Sculpting the bacterial cell. Current Biology 19: 812–822.

Margolin W (2009b) Bacterial division: a new way to box in the ring. Current Biology 19: 881–884.

Martos A, Jimenez M, Rivas G et al. (2012) Towards a bottom‐up reconstitution of bacterial cell division. Trends in Cell Biology 22: 634–643.

Mattei PJ, Neves D and Dessen A (2010) Bridging cell wall biosynthesis and bacterial morphogenesis. Current Opinion in Structural Biology 20: 749–755.

Mohammadi T, van Dam V, Sijbrandi R et al. (2011) Identification of FtsW as a transporter of lipid‐linked cell wall precursors across the membrane. EMBO Journal 30: 1425–1432.

Natale P, Pazos M and Vicente M (2013) The Escherichia coli divisome: born to divide. Environmental Microbiology 15: 3169–3182.

Osawa M, Anderson DE and Erickson HP (2008) Reconstitution of contractile FtsZ rings in liposomes. Science 320: 792–794.

Osawa M and Erickson HP (2013) Liposome division by a simple bacterial division machinery. Proceedings of the National Academy of Sciences of the USA 110: 11000–11004.

Pazos M, Natale P, Margolin W et al. (2013) Interactions among the early Escherichia coli divisome proteins revealed by bimolecular fluorescence complementation. Environmental Microbiology 15: 3282–3291.

Pichoff S and Lutkenhaus J (2002) Unique and overlapping roles for ZipA and FtsA in septal ring assembly in Escherichia coli. EMBO Journal 21: 685–693.

Pichoff S and Lutkenhaus J (2005) Tethering the Z ring to the membrane through a conserved membrane targeting sequence in FtsA. Molecular Microbiology 55: 1722–1734.

Rico AI, Krupka M and Vicente M (2013) In the beginning, Escherichia coli assembled the proto‐ring: an initial phase of division. Journal of Biological Chemistry 288: 20830–20836.

Rowlett VW and Margolin W (2013) The bacterial Min system. Current Biology 23: R553–R556.

Stouf M, Meile JC and Cornet F (2013) FtsK actively segregates sister chromosomes in Escherichia coli. Proceedings of the National Academy of Sciences of the USA 110: 11157–11162.

Strauss MP, Liew AT, Turnbull L et al. (2012) 3D‐SIM super resolution microscopy reveals a bead‐like arrangement for FtsZ and the division machinery: implications for triggering cytokinesis. PLoS Biology 10: e1001389.

Szwedziak P, Wang Q, Freund SM et al. (2012) FtsA forms actin‐like protofilaments. EMBO Journal 31: 2249–2260.

Thiel A, Valens M, Vallet‐Gely I et al. (2012) Long‐range chromosome organization in E. coli: a site‐specific system isolates the Ter macrodomain. PLoS Genetics 8: e1002672.

Tonthat NK, Milam SL, Chinnam N et al. (2013) SlmA forms a higher‐order structure on DNA that inhibits cytokinetic Z‐ring formation over the nucleoid. Proceedings of the National Academy of Sciences of the USA 110: 10586–10591.

Vollmer W, Blanot D and de Pedro MA (2008) Peptidoglycan structure and architecture. FEMS Microbiology Reviews 32: 149–167.

Yang DC, Peters NT, Parzych KR et al. (2011) An ATP‐binding cassette transporter‐like complex governs cell‐wall hydrolysis at the bacterial cytokinetic ring. Proceedings of the National Academy of Sciences of the USA 108: E1052–E1060.

Zieske K and Schwille P (2013) Reconstitution of pole‐to‐pole oscillations of Min proteins in microengineered polydimethylsiloxane compartments. Angewandte Chemie International Edition in English 52: 459–462.

Further Reading

Egan AJ and Vollmer W (2012) The physiology of bacterial cell division. Annals of the New York Academy of Sciences 1277: 8–28.

Huang KH, Durand‐Heredia J and Janakiraman A (2013) FtsZ ring stability: of bundles, tubules, crosslinks and curves. Journal of Bacteriology 195: 1859–1868.

Leonard AC and Grimwade JE (2011) Regulation of DnaA assembly and activity: taking directions from the genome. Annual Review of Microbiology 65: 19–35.

Reyes‐Lamothe R, Nicolas E and Sherratt DJ (2012) Chromosome replication and segregation in bacteria. Annual Review of Genetics 46: 121–143.

Typas A, Banzhaf M, Gross CA and Vollmer W (2011) From the regulation of peptidoglycan synthesis to bacterial growth and morphology Nature Reviews Microbiology 10: 123–136.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Margolin, William(Feb 2014) Binary Fission in Bacteria. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001420.pub2]