Bacterial Cell Division

Abstract

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 .
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Further Reading

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

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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. http://www.els.net [doi: 10.1002/9780470015902.a0000294.pub3]