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  • Review Article
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Regulation of peptidoglycan synthesis and remodelling

Abstract

Bacteria surround their cell membrane with a net-like peptidoglycan layer, called sacculus, to protect the cell from bursting and maintain its cell shape. Sacculus growth during elongation and cell division is mediated by dynamic and transient multiprotein complexes, the elongasome and divisome, respectively. In this Review we present our current understanding of how peptidoglycan synthases are regulated by multiple and specific interactions with cell morphogenesis proteins that are linked to a dynamic cytoskeletal protein, either the actin-like MreB or the tubulin-like FtsZ. Several peptidoglycan synthases and hydrolases require activation by outer-membrane-anchored lipoproteins. We also discuss how bacteria achieve robust cell wall growth under different conditions and stresses by maintaining multiple peptidoglycan enzymes and regulators as well as different peptidoglycan growth mechanisms, and we present the emerging role of ld-transpeptidases in peptidoglycan remodelling.

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Fig. 1: Peptidoglycan synthesis, cleavage and modification.
Fig. 2: Lipid II flipping and peptidoglycan synthesis during elongation and division.
Fig. 3: Emerging themes in peptidoglycan synthase regulation.
Fig. 4: Peptidoglycan remodelling in response to stress.

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Acknowledgements

This work was supported by Wellcome Trust Senior Investigator Awards (to W.V. (101824/Z/13/Z) and J.E. (209500)).

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Glossary

Turgor

Force pushing the cytoplasmic membrane against the cell wall, caused by the osmotic flow of water into the cytoplasm.

Spore cortex

A specialized spore cell wall layer uniquely deposited inward from the enveloping mother cell compartment.

Proton motive force

(PMF). Force that promotes the movement of protons across membranes down the electrochemical potential gradient, in most cells generated by an electron transport chain that acts as a proton pump.

Elongasome

Dynamic multiprotein complex responsible for peptidoglycan synthesis in the lateral wall of many rod-shaped bacteria.

Actin

Family of cytoskeletal proteins that dynamically form microfilaments to perform a range of important cellular processes in both eukaryotes and prokaryotes. The prokaryotic actin-like MreB is part of the elongasome in many rod-shaped bacteria.

Divisome

Transient and dynamic multiprotein complex that divides a bacterial cell.

Tubulin

Family of cytoskeletal proteins that form microtubules in eukaryotes. The tubulin-like FtsZ forms dynamic filaments to organize cell division in bacteria.

Bactofilins

Bacterial cytoskeletal proteins that form sheet-like structures or filaments near the cell membrane to guide morphogentic processes.

3D-struc tured illumination microscopy

(3D-SIM). An imaging technique based on the use of spatially structured excitation illumination; it allows reconstruction of super-resolution images with approximately twice the resolution of regular, diffraction-limited microscopy (down to ~110 nm).

Photoactivated localization microscopy

(PALM). Super-resolution microscopy technique based on repetitive imaging of stochastically photoactivatable or photoswitchable fluorescent proteins; it can achieve a resolution of 10–20 nm.

Total internal reflection fluorescence microscopy

(TIRF). Uses an evanescent wave (a very thin electromagnetic field) to selectively excite and image fluorophores within a 100-nm to 200-nm distance from the coverslip–specimen interface.

RpoS

Alternative sigma factor for stationary-phase gene expression.

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Egan, A.J.F., Errington, J. & Vollmer, W. Regulation of peptidoglycan synthesis and remodelling. Nat Rev Microbiol 18, 446–460 (2020). https://doi.org/10.1038/s41579-020-0366-3

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