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  • Review Article
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Splitsville: structural and functional insights into the dynamic bacterial Z ring

Nature Reviews Microbiology volume 14, pages 305–319 (2016)Cite this article

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A Corrigendum to this article was published on 25 April 2016

This article has been updated

Key Points

  • All cells must divide to proliferate, and most bacteria divide by splitting themselves into two during cytokinesis. Many bacteria divide by splitting into approximately equal halves in a process called binary fission. Cytokinesis in bacteria is achieved by the divisome, a dedicated protein machine that is located at the site of cell division. Recent advances in ultrastructural imaging, biochemistry and genetics of Escherichia coli and other model bacterial species have helped to refine models of divisome function and regulation.

  • FtsZ, the bacterial homologue of tubulin, is the principal driver of bacterial cytokinesis. In vitro, FtsZ assembles into single protofilaments in the presence of GTP. In vivo, these protofilaments loosely assemble to encircle the cell at the site of division — called the Z ring — and are positioned there by species-specific spatial positioning proteins.

  • As FtsZ is a soluble protein, FtsZ protofilaments must be tethered to the inner surface of the cytoplasmic membrane by additional proteins, including FtsA and ZipA in E. coli. This complex of FtsZ and membrane tethers is called the proto-ring and has highly dynamic behaviour.

  • Although they do not form microtubules, FtsZ protofilaments self-associate to form bundles, either through interactions with other FtsZ subunits or with several FtsZ-binding proteins that enhance bundling, including ZipA and Zap proteins. These lateral interactions between FtsZ protofilaments may be important for the ability of FtsZ to divide a cell.

  • FtsA, a bacterial homologue of actin, is a key connector between the Z ring and other proteins of the divisome, all of which span the membrane and some of which bind to the peptidoglycan layer. Once the divisome is completely assembled, it coordinates the inward constriction of the Z ring and cytoplasmic membrane with the synthesis of the cell division septum, which is composed of peptidoglycan. FtsA is a key player in this coordination, which probably involves feedback signalling between the peptidoglycan-binding divisome proteins and the Z ring. Biochemical characterization of FtsA remains a major challenge.

  • In addition to signalling in the divisome during the process of cytokinesis, the divisome is regulated by mechanical, metabolic and stress inputs. FtsZ is a major target for these regulators, but other divisome proteins are also targets. Understanding how divisome proteins are inhibited or stimulated will be valuable in the future design of divisome-specific antimicrobial compounds.

Abstract

Bacteria must divide to increase in number and colonize their niche. Binary fission is the most widespread means of bacterial cell division, but even this relatively simple mechanism has many variations on a theme. In most bacteria, the tubulin homologue FtsZ assembles into a ring structure, termed the Z ring, at the site of cytokinesis and recruits additional proteins to form a large protein machine — the divisome — that spans the membrane. In this Review, we discuss current insights into the regulation of the assembly of the Z ring and how the divisome drives membrane invagination and septal cell wall growth while flexibly responding to various cellular inputs.

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Figure 1: Overview of bacterial cytokinesis.
Figure 2: Placement and tethering of the Z ring.
Figure 3: Proto-ring ultrastructure in E. coli.
Figure 4: The constricting divisome in vivo and reconstituted in vitro.
Figure 5: The regulation of divisome activity by stress and nutritional status.

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Change history

  • 25 April 2016

    Nature Reviews Microbiology 14, 305–319 (2016). In the sixth paragraph of the section 'FtsA and the dynamics of proto-ring assembly', the sentence “Finally, an FtsZ mutant with decreased self-bundling in vitro (FtsZ-E93R) has reduced function in cell division50, 51.” should have read “However, an FtsZ mutant with increased self-bundling in vitro (FtsZ-E93R) has reduced function in cell division50,51.” The authors apologize to the readers for any misunderstanding caused.

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Acknowledgements

The authors gratefully acknowledge support from the US National Institute of General Medical Sciences (R01-GM61074 to W.M.) and the US National Institute of Research Resources (S10RR029552) for the use of the 3D-SIM microscope.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, McGovern Medical School, 6431 Fannin Street, Houston, 77030, Texas, USA

    Daniel P. Haeusser & William Margolin

  2. Biology Department, Canisius College, 2001 Main Street, Buffalo, 14208, New York, USA

    Daniel P. Haeusser

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Correspondence to William Margolin.

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Glossary

Cytokinesis

The splitting of the contents of a cell to make two cells.

Nucleoids

The nucleus-like organized structures of bacterial chromosomes.

Mycelium

A filamentous, branched network of multinucleate cells growing on a surface.

Lipid II flippase

A membrane protein that transfers lipid-linked peptidoglycan precursors from the inner leaflet of the cytoplasmic membrane to the outer leaflet of the cytoplasmic membrane, so that they can be incorporated into the cell wall.

Sidewall

The peptidoglycan layer in many rod-shaped bacteria that is active in elongating the cell and comprises most of the straight wall of the cell with the exception of cell poles and the division septum.

Thermosensitive ftsZ mutant

A point mutation in the ftsZ gene that permits normal growth and division at 30 °C but stops division at 42 °C despite continued growth, resulting in filamentous, multinucleate cells (hence the term fts for filamentous temperature sensitive mutants).

Central metabolism

Metabolic pathways, such as the tricarboxylic acid (TCA) cycle, that provide precursor metabolites for all other pathways that are required for growth.

ClpXP

A protein chaperone–protease machine that targets certain proteins for unfolding and degradation.

SOS response

Induced by DNA damage, the SOS response is a stress response that results in the expression of many genes that are important for the protection of chromosomal DNA.

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Haeusser, D., Margolin, W. Splitsville: structural and functional insights into the dynamic bacterial Z ring. Nat Rev Microbiol 14, 305–319 (2016). https://doi.org/10.1038/nrmicro.2016.26

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