Bacterial Cell Division


Escherichia coli assembles a contractile ring, the divisome, in its envelope at the middle of its length exactly when it is needed for division. Its main component, FtsZ, is a cytoplasmic protein lacking the ability to be positioned by itself in the membrane. Additional proteins regulate either the action, the positioning or the stability of FtsZ by interacting with a unique region called the FtsZ ‘central hub’. The assembly of the divisome is initiated by a proto‐ring, in which ZipA and FtsA are two proteins that use the central hub for attaching FtsZ to the membrane. Polymerisation of FtsZ is blocked at the poles by the MinCDE proteins and also prevented by SlmA to occur at places adjacent to the nucleoid. After nucleoid segregation, the divisome becomes functional at midcell where it triggers invagination of the membrane and the production of septal peptidoglycan, leading ultimately to an efficient cell division.

Key Concepts

  • Division depends on a cytoskeletal element (FtsZ ring) that functions as a scaffold to recruit additional division proteins.
  • Spatial regulation of the FtsZ‐ring placement involves positioning inhibitors of FtsZ in the cell to prevent FtsZ polymers from assembling at the poles or across unsegregated nucleoids.
  • Several complexes that effect the division process localise at specific places of the cell at precise moments after growth and nucleoid segregation.
  • The interactions of FtsZ, a cytoplasmic protein, with the proto‐ring anchors, FtsA and ZipA, serve to associate it to the cytoplasmic membrane forming the proto‐ring, the initial precursor of the division machinery.
  • The central hub of FtsZ is key to the action of the FtsZ regulatory proteins FtsA, FtsE, FtsX, ZipA, ZapC, ZapD, MinC, SlmA and ClpX.
  • The Min proteins generate an oscillatory pattern in artificial systems, and FtsZ filaments can form rings when attached to a lipid bilayer that has a cylindrical shape.
  • PBP3‐independent peptidoglycan synthesis (PIPS) prior to the production of septal peptidoglycan directly connects cytoplasmic division proteins with peptidoglycan synthesis in the bacterial periplasm.

Keywords: FtsZ; septum; central hub; FtsZ ring; preseptal peptidoglycan; binary fission

Figure 1. The assembly and location of the division machinery in E. coli. Ten of the essential proteins that gather together at the midcell to form a division ring, a structure that effects septation, forming part of the divisome, are illustrated in line (a). The additional FtsEX complex, located in between FtsK and the FtsQBL complex, is not represented. The process involves complexes in which assembly proceeds in a concerted way (line a); see text for further explanation. A proto‐ring (line b), formed by interaction between three proteins (FtsZ, FtsA and ZipA) assembling on the cytoplasmic membrane, is an early event (line d) that is followed by the addition of FtsK to form the cytoplasmic ring (line c). At a late assembly stage (line d), additional elements forming a periplasmic connector (FtsQ, FtsB and FtsL) and the proteins of the ring involved in manufacturing septal peptidoglycan (FtsW and FtsI) are added, followed by FtsN. Together, they form a ring protruding into the periplasm and connecting with the peptidoglycan layer (line c). Late assembly events might occur even in the absence of elements such as FtsA that assemble earlier (line e). The intracellular locations of protein assemblies involved in E. coli division are shown in line (f). Several complexes that effect the division process localise at specific places of the cell at precise moments after growth and nucleoid segregation. A partly divided cell is schematically drawn with two fully replicated and segregated nucleoids (mauve ovoids). A part of the cell envelope has been removed in the right‐hand side daughter cell to add spatial information. The outer membrane is the border between the cell and the medium and is shown as a continuous line at the poles and at the section plane. The discontinuous blue line represents the cytoplasmic membrane. The division ring is depicted in pink. The cytoplasmic membrane at the section plane has been drawn as continuous for aesthetics. For simplicity, the peptidoglycan layer, synthetised by the elongasome in the space between the two membranes (the periplasm), is not shown in this illustration. Fts protein names have been abbreviated by excluding Fts. Zip = ZipA. Vicente and Rico . Reproduced with permission of John Wiley and Sons.
Figure 2. The E. coli proto‐ring. The interactions of FtsZ, a cytoplasmic protein, with the proto‐ring anchors, FtsA and ZipA, serve to associate it to the cytoplasmic membrane forming the proto‐ring, the initial precursor of the division machinery. The FtsZ monomers (in which the central hub is not shown for simplicity) form polymers in which GTPase active sites, represented as red circles, are formed in the intersection between two monomers. The hydrolytic activity is needed for the function of the FtsZ ring in septation, probably by fuelling constriction of the envelope.
Figure 3. Interactions of the FtsZ regulators at the FtsZ central hub. FtsZ, the main component of the machinery responsible for bacterial division, drawn in this figure with its central hub extended, is assisted by a set of regulatory proteins. Activators are framed in blue. FtsA, FtsE, FtsX and ZipA anchor it to the membrane and ZapC and ZapD stabilise its structure. Negative regulators are framed in red. MinC and SlmA serve to localise FtsZ at midcell by preventing polymerisation at other sites, whereas ClpX contributes to dispose of spent molecules when constriction is over. Other names mark the location of additional protein complexes involved in division. Other elements are drawn as in Figure .
Figure 4. Schematic overview of the MinCDE oscillation. The presence of the MinCDE complex blocks polymerisation of FtSZ at the left‐hand side pole of the dividing cell. MinD (blue circle) is bound to the cytoplasmic membrane by an amphipathic helix (black rod). The binding of MinC (red octagon) to the membrane‐bound MinD blocks the formation of FtsZ polymers in its neighbourhood. The displacement of the MinE ring (green teardrop) to chase MinD initiates the pole to pole oscillation of the complex. First, the hydrolysis of ATP by MinD releases MinCD from the membrane. Once in the cytoplasm, the three Min components migrate to the pole further away from their initial location where they build up new MinCD inhibitory complexes (right‐hand side of the dividing cell) that in their turn will be dismantled once MinE follows the migration to the distal pole. This pole to pole oscillation of MinCD blocks division at the two poles and allows FtsZ to polymerise at midcell once the nucleoids are segregated and the nucleoid occlusion mediated by SlmA (shown in Figure 4) is released by the absence of SBS, the chromosomal SlmA‐binding sequences. See text for further details. Other symbols as in Figure .
Figure 5. PBP3‐independent peptidoglycan synthesis (PIPS). Prior to the production of septal peptidoglycan (pink continuous and discontinuous arcs), a synthesis of lateral peptidoglycan (pink discontinuous line) occurs in which the activity of PBP3 is dispensable. The activities involved in PIPS localise at midcell once the nucleoids (mauve oval segments) are segregated. Approximate location occupied by the positive keepers of the ring is indicated. Peptidoglycan synthases PBP1A or PBP1B (1A/B); other protein names are abbreviated as in Figure .


Balasubramanian A, Markovski M, Hoskins JR, Doyle SM and Wickner S (2019) Hsp90 of modulates assembly of FtsZ, the bacterial tubulin homolog. Proc Natl Acad Sci U S A 116: 12285–12294.

Bendezu FO and de Boer PA (2008) Conditional lethality, division defects, membrane involution, and endocytosis in mre and mrd shape mutants of Escherichia coli. Journal of Bacteriology 190: 1792–1811.

Bhattacharya A, Ray S, Singh D, Dhaked HP and Panda D (2015) ZapC promotes assembly and stability of FtsZ filaments by binding at a different site on FtsZ than ZipA. International Journal of Biological Macromolecules 81: 435–442.

Bisson‐Filho AW, Hsu YP, Squyres GR, et al. (2017) Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science 355: 739–743.

Bratton BP, Shaevitz JW, Gitai Z and Morgenstein RM (2018) MreB polymers and curvature localization are enhanced by RodZ and predict E. coli's cylindrical uniformity. Nature Communications 9: 2797.

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

Cho H, Mcmanus HR, Dove SL and Bernhardt TG (2011) Nucleoid occlusion factor SlmA is a DNA‐activated FtsZ polymerization antagonist. Proceedings of the National Academy of Sciences of the United States of America 108: 3773–3778.

Colavin A, Shi H and Huang KC (2018) RodZ modulates geometric localization of the bacterial actin MreB to regulate cell shape. Nature Communications 9: 1280.

Coltharp C, Buss J, Plumer TM and Xiao J (2016) Defining the rate‐limiting processes of bacterial cytokinesis. Proceedings of the National Academy of Sciences of the United States of America 113: E1044–E1053.

Cordell SC, Robinson EJ and Löwe J (2003) Crystal structure of the SOS cell division inhibitor SulA and in complex with FtsZ. Proceedings of the National Academy of Sciences of the United States of America 100: 7889–7894.

Dajkovic A, Mukherjee A and Lutkenhaus J (2008) Investigation of regulation of FtsZ assembly by SulA and development of a model for FtsZ polymerization. Journal of Bacteriology 190: 2513–2526.

De Boer PA, Crossley RE and Rothfield LI (1989) 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.

Du S, Pichoff S and Lutkenhaus J (2016) FtsEX acts on FtsA to regulate divisome assembly and activity. Proceedings of the National Academy of Sciences of the United States of America 113: E5052–E5061.

Du S, Henke W, Pichoff S and Lutkenhaus J (2019) How FtsEX localizes to the Z ring and interacts with FtsA to regulate cell division. Molecular Microbiology.

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

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.

Furusato T, Horie F, Matsubayashi H, et al. (2018) De novo synthesis of basal bacterial cell division proteins FtsZ, FtsA, and ZipA inside giant vesicles. ACS Synthetic Biology 7: 953–961.

Hernández‐Rocamora VM, Reija B, García C, et al. (2012) Dynamic interaction of the Escherichia coli cell division ZipA and FtsZ proteins evidenced in nanodiscs. The Journal of Biological Chemistry 287: 30097–30104.

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

Kretschmer S, Ganzinger KA, Franquelim HG and Schwille P (2019) Synthetic cell division via membrane‐transforming molecular assemblies. BMC Biology 17: 43.

Lan G, Daniels BR, Dobrowsky TM, Wirtz D and Sun SX (2009) Condensation of FtsZ filaments can drive bacterial cell division. Proceedings of the National Academy of Sciences of the United States of America 106: 121–126.

Litschel T, Ramm B, Maas R, Heymann M and Schwille P (2018) Beating vesicles: encapsulated protein oscillations cause dynamic membrane deformations. Angewandte Chemie (International Ed. in English) 57: 16286–16290.

Liu B, Persons L, Lee L and De Boer PA (2015) Roles for both FtsA and the FtsBLQ subcomplex in FtsN‐stimulated cell constriction in Escherichia coli. Molecular Microbiology 95: 945–970.

Loose M and Mitchison TJ (2014) The bacterial cell division proteins FtsA and FtsZ self‐organize into dynamic cytoskeletal patterns. Nature Cell Biology 16: 38–46.

López‐Montero I, López‐Navajas P, Mingorance J, et al. (2013) Intrinsic disorder of the bacterial cell division protein ZipA: coil‐to‐brush conformational transition. The FASEB Journal 27: 3363–3375.

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

Maguin E, Lutkenhaus J and D'ari R (1986) Reversibility of SOS‐associated division inhibition in Escherichia coli. Journal of Bacteriology 166: 733–738.

Mukherjee A and Lutkenhaus J (1999) Analysis of FtsZ assembly by light scattering and determination of the role of divalent metal cations. Journal of Bacteriology 181: 823–832.

Nanninga N (1991) Cell division and peptidoglycan assembly in Escherichia coli. Molecular Microbiology 5: 791–795.

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

Oliva MA, Trambaiolo D and Lowe J (2007) Structural insights into the conformational variability of FtsZ. Journal of Molecular Biology 373: 1229–1242.

Ortiz C, Kureisaite‐Ciziene D, Schmitz F, et al. (2015) Crystal structure of the Z‐ring associated cell division protein ZapC from Escherichia coli. FEBS Letters 589: 3822–3828.

Ortiz C, Natale P, Cueto L and Vicente M (2016) The keepers of the ring: regulators of FtsZ assembly. FEMS Microbiology Reviews 40: 57–67.

Ortiz Cabello C (2015) Molecular Interaction of the Cell Division Protein ZapC, a Regulator of the Escherichia coli FtsZ‐ring Assembly. PhD, Universidad Autonoma de Madrid (UAM); Centro Nacional de Biotecnología (CNB‐CSIC).

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 United States of America 110: 11000–11004.

Pazos M, Casanova M, Palacios P, et al. (2014) FtsZ placement in nucleoid‐free bacteria. PLoS One 9: e91984.

Pazos M, Natale P and Vicente M (2013) A specific role for the ZipA protein in cell division: stabilization of the FtsZ protein. J Biol Chem 288: 3219–3226.

Pazos M, Peters K, Casanova M, et al. (2018) Z‐ring membrane anchors associate with cell wall synthases to initiate bacterial cell division. Nature Communications 9: 5090.

Pazos M and Peters K (2019) Peptidoglycan. Sub‐Cellular Biochemistry 92: 127–168.

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

Roach EJ, Wroblewski C, Seidel L, et al. (2016) Structure and mutational analyses of Escherichia coli ZapD reveal charged residues involved in FtsZ filament bundling. Journal of Bacteriology 198: 1683–1693.

Sánchez‐Gorostiaga A, Palacios P, Martínez‐Arteaga R, et al. (2016) Life without division: physiology of Escherichia coli FtsZ‐deprived filaments. MBio 7: e01620‐16.

Schmidt KL, Peterson ND, Kustusch RJ, et al. (2004) A predicted ABC transporter, FtsEX, is needed for cell division in Escherichia coli. Journal of Bacteriology 186: 785–793.

Schumacher MA, Huang KH, Zeng W and Janakiraman A (2017) Structure of the Z Ring‐associated Protein, ZapD, bound to the C‐terminal domain of the tubulin‐like protein, FtsZ, suggests mechanism of Z ring stabilization through FtsZ cross‐linking. The Journal of Biological Chemistry 292: 3740–3750.

Söderström B, Chan H, Shilling PJ, Skoglund U and Daley DO (2018) Spatial separation of FtsZ and FtsN during cell division. Molecular Microbiology 107: 387–401.

Tsang MJ, Yakhnina AA and Bernhardt TG (2017) NlpD links cell wall remodeling and outer membrane invagination during cytokinesis in Escherichia coli. PLoS Genetics 13: e1006888.

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.

Vicente M and Rico AI (2006) The order of the ring: assembly of Escherichia coli cell division components. Molecular Microbiology 61: 5–8.

Wagstaff JM, Tsim M, Oliva MA, et al. (2017) A polymerization‐associated structural switch in FtsZ that enables treadmilling of model filaments. MBio 8.

Wu F, van Schie BGC, Keymer JE and Dekker C (2015) Symmetry and scale orient Min protein patterns in shaped bacterial sculptures. Nature Nanotechnology 10 (8): 719–726.

Xiao J and Goley ED (2016) Redefining the roles of the FtsZ‐ring in bacterial cytokinesis. Current Opinion in Microbiology 34: 90–96.

Further Reading

De Boer PA (2016) Bacterial physiology: life minus Z. Nature Microbiology 1: 16121.

Den Blaauwen T and Luirink J (2019) Checks and balances in bacterial cell division. MBio 10.

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

Lutkenhaus J (2007) Assembly dynamics of the bacterial MinCDE system and spatial regulation of the Z ring. Annual Review of Biochemistry 76: 539–562.

Schoenemann KM and Margolin W (2017) Bacterial division: FtsZ treadmills to build a beautiful wall. Current Biology 27: R301–R303.

Tsang MJ and Bernhardt TG (2015) Guiding divisome assembly and controlling its activity. Current Opinion in Microbiology 24: 60–65.

Typas A, Banzhaf M, Gross CA and Vollmer W (2012) From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nature Reviews Microbiology 10: 123–136.

Vicente M, Alvarez J and Martínez‐Arteaga R (2004) How similar cell division genes are located and behave in different bacteria. In: Vicente M, Tamames J, Valencia A and Mingorance J (eds) Molecules in Time and Space. Bacterial Shape, Division and Phylogeny. Kluwer Academic/Plenum Publishers: New York.

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Natale, Paolo, and Vicente, Miguel(May 2020) Bacterial Cell Division. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000294.pub3]