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  • Review Article
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From the regulation of peptidoglycan synthesis to bacterial growth and morphology

Nature Reviews Microbiology volume 10, pages 123–136 (2012)Cite this article

Subjects

Key Points

  • Peptidoglycan synthesis is regulated at multiple levels to ensure shape-maintaining growth and cell division.

  • Peptidoglycan synthases and hydrolases coordinate to enlarge the sacculus. Coordinated enzyme activity is also required for cell division and morphogenesis.

  • Peptidoglycan synthesis and the localization and movement of cytoskeletal elements are interdependent.

  • Peptidoglycan synthases and hydrolases are also regulated by outer-membrane proteins.

  • Peptidoglycan growth is sensitive to mechanical force.

  • Peptidoglycan is remodelled in a growth-dependent manner, and its growth is tied to metabolic inputs.

Abstract

How bacteria grow and divide while retaining a defined shape is a fundamental question in microbiology, but technological advances are now driving a new understanding of how the shape-maintaining bacterial peptidoglycan sacculus grows. In this Review, we highlight the relationship between peptidoglycan synthesis complexes and cytoskeletal elements, as well as recent evidence that peptidoglycan growth is regulated from outside the sacculus in Gram-negative bacteria. We also discuss how growth of the sacculus is sensitive to mechanical force and nutritional status, and describe the roles of peptidoglycan hydrolases in generating cell shape and of D-amino acids in sacculus remodelling.

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Figure 1: Peptidoglycan synthesis and cleavage.
Figure 2: Different peptidoglycan synthesis complexes are active at different stages of the Escherichia coli cell cycle.
Figure 3: Force generation by cytoskeletal elements.
Figure 4: Species-specific non-catalytic regions in penicillin-binding proteins.
Figure 5: Regulation of peptidoglycan synthesis by outer-membrane proteins.

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Acknowledgements

This work was supported by grants from the UK Biotechnology and Biological Sciences Research Council (BB/G015902/1 and BBI020012/1 to W.V.), the European Commission (DIVINOCELL HEALTH-F3-2009-223,431 to W.V.), the Royal Society (to W.V.) and the US National Institutes of Health (R01 GM085697, ARRA GM085697-01S1 and R01 GM036278 to C.A.G., and K99GM092984 to A.T.).

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Authors and Affiliations

  1. Department of Microbiology & Immunology, University of California, San Francisco

    Athanasios Typas & Carol A. Gross

  2. Genome Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, 69117, Germany

    Athanasios Typas

  3. Harvard Medical School, Immune Disease Institute, 3 Blackfan Circle, Boston, 02115, Massachusetts, USA

    Manuel Banzhaf

  4. Department of Cell and Tissue Biology, University of California, San Francisco, 600 16th Street, San Francisco, 94158, California, USA

    Carol A. Gross

  5. Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Richardson Road, Newcastle upon Tyne, NE2 4AX, UK

    Waldemar Vollmer

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Glossary

Sacculus

A bag-like macromolecule that is made of peptidoglycan chains crosslinked by short peptides. The sacculus completely encases the cytoplasmic membrane in most bacteria, and isolated sacculi retain the shape of the bacterial cell.

Bacterial cytoskeleton

A filamentous and often dynamic cytoplasmic structure that includes bacterial structural homologues of actin, tubulin or intermediate filaments and is essential for bacterial growth, motility, cell division, morphology and DNA segregation.

Actin

A eukaryotic cytoskeletal protein with ATPase activity. MreB and ParM, two bacterial proteins involved in cell elongation and plasmid partitioning, respectively, are distant actin homologues.

Tubulin

A cytoskeletal protein that forms microtubules in eukaryotes; the bacterial tubulin-like protein, FtsZ, is a GTPase and forms dynamic filaments to drive cell division.

Penicillin-binding proteins

(PBPs). A protein family involved in the synthesis (the class A and class B PBPs) or hydrolysis (the class C PBPs) of D-amino acid–D-amino acid peptide bonds. They contain an active-site Ser residue that participates in the transfer of an acyl compound to an amino group or water. PBPs are the targets of β-lactam antibiotics (such as penicillin). Pathogen resistance to β-lactams can be caused by low-affinity PBPs.

β-lactam antibiotics

An important class of antibiotics, members of which contain a β-lactam ring and inhibit peptidoglycan synthesis by covalent binding to the active-site Ser of penicillin-binding proteins.

Autolysins

Proteins that are located in the periplasm of Gram-negative bacteria or in the cell wall of Gram-positive bacteria and can lyse the cell using their peptidoglycan-hydrolysing activity. Autolysins can have muramidase, glucosaminidase, amidase and/or endopeptidase activity.

Electron cryotomography

(ECT). An electron microscopy technique that provides high-resolution pictures of an object from different angles, permitting its three-dimensional reconstitution; plunge-freezing of the samples prevents staining and fixation artefacts. In the case of the bacterial sacculus, ECT has yielded a nanometre-scale three-dimensional representation of the fine structure.

Intermediate filaments

Filaments formed by coiled-coil-rich cytoskeletal proteins, such as keratin. Crescentin is a bacterial version of an intermediate filament and is required for the bent cell shape of Caulobacter crescentus.

Blebbing

The release of vesicles from the outer membrane of Gram-negative bacteria. Blebbing occurs during normal growth and is enhanced in certain mutants that are impaired in cell division.

Lysozyme

An antibacterial enzyme that is produced in animals, plants, fungi and even bacteria and is capable of lysing sensitive bacteria by hydrolysing the N-acetylmuramic acid–N-acetylglucosamine bonds in peptidoglycan chains.

Type VI secretion systems

(T6SSs). A recently discovered secretion apparatus that is widely distributed in Gram-negative bacteria. Some of its components are similar to phage injection systems. The T6SS punctures both eukaryotic and bacterial cells, often injecting toxic effector proteins into them.

Turgor

The osmotic pressure of a compartment (here, the bacterial cytoplasm) that is due to the lower activity of water.

D-amino acids

Rare chiral forms (mirror structures) of the abundant L-amino acids that build proteins. D-amino acids are present in peptidoglycan and in some non-ribosomally synthesized antibiotics.

Atomic force microscopy

(AFM). A microscopy technique that uses a cantilever tip to scan the surface of a probe, either in direct contact or in oscillation mode, to produce topography images with nanometre-scale resolution.

Total internal reflection fluorescence microscopy

(TIRF microscopy). A fluorescence microscopy technique that uses an evanescent wave to selectively excite a fluorophore in a small area of a specimen adjacent to a glass–water interface to reduce background fluorescence. This technique provides a superior axial resolution.

Photoactivated localization microscopy

(PALM). A super-resolution fluorescence microscopy technique based on the controlled activation and sampling of subsets of photoconvertible fluorescent molecules in the sample. This technique can achieve 10–20 nm resolution.

Solid-state NMR spectroscopy

NMR spectroscopy of insoluble polymers. The technique requires rapid spinning of the sample at a certain 'magic' angle. It provides information on the structural flexibility of a polymer and the interactions of chemical entities within it (for example, amino acids or sugars in peptidoglycan sacculi).

Förster resonance energy transfer

(FRET). A technique that detects and characterizes the interaction between two molecules coupled to two fluorophores, by measuring the excitation of one fluorophore by the light emitted from the other. A positive FRET signal indicates a distance of less than 10 nm between the fluorophores.

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Typas, A., Banzhaf, M., Gross, C. et al. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Microbiol 10, 123–136 (2012). https://doi.org/10.1038/nrmicro2677

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