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Cited by 447Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

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Architecture of the dynamic fungal cell wall

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Gow, Neil A. R., Lenardon, Megan D.·2023·Nature Reviews Microbiology
DOI 10.1038/s41579-022-00796-9
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Abstract

The fungal cell wall is essential for growth and survival, and is a key target for antifungal drugs and the immune system. The cell wall must be robust but flexible, protective and shielding yet porous to nutrients and membrane vesicles and receptive to exogenous signals. Most fungi have a common inner wall skeleton of chitin and β-glucans that functions as a flexible viscoelastic frame to which a more diverse set of outer cell wall polymers and glycosylated proteins are attached. Whereas the inner wall largely determines shape and strength, the outer wall confers properties of hydrophobicity, adhesiveness, and chemical and immunological heterogeneity. The spatial organization and dynamic regulation of the wall in response to prevailing growth conditions enable fungi to thrive within changing, diverse and often hostile environments. Understanding this architecture provides opportunities to develop diagnostics and drugs to combat life-threatening fungal infections. In this Review, Gow and Lenardon describe how fungal cell walls are organized, focusing on the underlying architectural and mechanical principles that are required to deliver differing and bespoke biochemical and biophysical attributes.

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Fig. 1 The cell wall defines the shape of the fungus. a | A myriad of microscopic and macroscopic forms of fungal architectures can be constructed by regulation and modification of the pattern of cell wall deposition via isotropic growth or polarized growth, and the processes of compartmentalization and aggregation leading to multicellularity. b -n | These fundamental processes generate the shapes and forms of unicellular yeasts (part b ), pseudohyphae (part c ) and filamentous mycelia (part d ), as well as multicellular fungal structures exemplified by
Fig. 1 The cell wall defines the shape of the fungus. a | A myriad of microscopic and macroscopic forms of fungal architectures can be constructed by regulation and modification of the pattern of cell wall deposition via isotropic growth or polarized growth, and the processes of compartmentalization and aggregation leading to multicellularity. b -n | These fundamental processes generate the shapes and forms of unicellular yeasts (part b ), pseudohyphae (part c ) and filamentous mycelia (part d ), as well as multicellular fungal structures exemplified byCC-BY · From the PDF
Fig. 2 Architecture of the fungal cell wall. a | Scalar model of the cell wall of Candida albicans showing the outer Nmannan frond of microfibrils in the outer wall and the inner wall of antiparallel chitin microfibrils and β -1,3-glucan triple helices and β -1,6-glucan bridges between the cell wall proteins and β -1,3-glucan 33 . Glycosylphosphatidylinositol (GPI)-anchored proteins are covalently attached to β -1,6-glucan and to the flexible β -1,3-glucan-chitin network. Pir cell wall proteins are less common than GPI-anchored proteins and are ether-linked to β -1,3-glucan via mannose. O-Linked mannans are short, ether-linked oligosaccharides that act to stabilize Ser-Thr rich stem-like
Fig. 2 Architecture of the fungal cell wall. a | Scalar model of the cell wall of Candida albicans showing the outer Nmannan frond of microfibrils in the outer wall and the inner wall of antiparallel chitin microfibrils and β -1,3-glucan triple helices and β -1,6-glucan bridges between the cell wall proteins and β -1,3-glucan 33 . Glycosylphosphatidylinositol (GPI)-anchored proteins are covalently attached to β -1,6-glucan and to the flexible β -1,3-glucan-chitin network. Pir cell wall proteins are less common than GPI-anchored proteins and are ether-linked to β -1,3-glucan via mannose. O-Linked mannans are short, ether-linked oligosaccharides that act to stabilize Ser-Thr rich stem-likeCC-BY · From the PDF
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Parts a , b and c adapted from ref. 30 , Springer Nature Limited. Part d reprinted with permission from ref. 25 , Wiley. Parts e , g and h reprinted with permission from ref. 132 , Journal of Cell Science. Part f courtesy of L. Walker, University of Aberdeen, Scotland, and N.G.
Parts a , b and c adapted from ref. 30 , Springer Nature Limited. Part d reprinted with permission from ref. 25 , Wiley. Parts e , g and h reprinted with permission from ref. 132 , Journal of Cell Science. Part f courtesy of L. Walker, University of Aberdeen, Scotland, and N.G.CC-BY · From the PDF
Image 5
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Fig. 3 From microstructure to nanostructure of the cell wall. a | T ransmission electron micrograph of a Candida albicans cell. b | Magnification of part a to reveal the inner and outer cell walls 98 . c | Hyr1 protein localization by monoclonal antibody-colloidal gold labelling (Hry1) at the base of the frond of mannan fibrils (indicated by arrows) 128 . d | Scalar model of C. albicans cell wall based on transmission electron micrographs and tomograms, analysis of mutants and enzymatic debridement studies showing chitin, β -glucan and mannoproteins in the inner layer and mannan fibrils in the outer layer 33 . e , f | Computer modelling of an electron tomogram demonstrating the spine and branch architecture of an N -mannan fibril (part e ) corresponding to the structure of N -mannan determined by nuclear magnetic resonance spectroscopy (part f ) with an α -1,6-mannan backbone and α -1,3-mannose, α -1,2-mannose and β -1,2-mannose side chains 33 . The phosphate groups linking β -1,2-mannosaccharides (black arrow) via a phosphodiester bond convey a negative charge to the cell wall. Measurements for part e as indicated. Part a courtesy of A. Brown, I. Brown and N.G., University of Exeter. Part b adapted from ref. 98 , Springer Nature Limited. Part c adapted from ref. 128 , Springer Nature Limited. Part d adapted from ref. 33 , CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Part e adapted from ref. 33 , Springer Nature Limited. Part f courtesy of N.G.
Fig. 3 From microstructure to nanostructure of the cell wall. a | T ransmission electron micrograph of a Candida albicans cell. b | Magnification of part a to reveal the inner and outer cell walls 98 . c | Hyr1 protein localization by monoclonal antibody-colloidal gold labelling (Hry1) at the base of the frond of mannan fibrils (indicated by arrows) 128 . d | Scalar model of C. albicans cell wall based on transmission electron micrographs and tomograms, analysis of mutants and enzymatic debridement studies showing chitin, β -glucan and mannoproteins in the inner layer and mannan fibrils in the outer layer 33 . e , f | Computer modelling of an electron tomogram demonstrating the spine and branch architecture of an N -mannan fibril (part e ) corresponding to the structure of N -mannan determined by nuclear magnetic resonance spectroscopy (part f ) with an α -1,6-mannan backbone and α -1,3-mannose, α -1,2-mannose and β -1,2-mannose side chains 33 . The phosphate groups linking β -1,2-mannosaccharides (black arrow) via a phosphodiester bond convey a negative charge to the cell wall. Measurements for part e as indicated. Part a courtesy of A. Brown, I. Brown and N.G., University of Exeter. Part b adapted from ref. 98 , Springer Nature Limited. Part c adapted from ref. 128 , Springer Nature Limited. Part d adapted from ref. 33 , CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Part e adapted from ref. 33 , Springer Nature Limited. Part f courtesy of N.G.CC-BY · From the PDF
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Metadata

Authors
Gow, N. A. R., & Lenardon, M. D.
Affiliations
  • University of Exeter (GB)
  • UNSW Sydney (AU)
Corresponding author
  • Gow, Neil A. R.
  • Lenardon, Megan D.
ORCID
Venue
Nature Reviews Microbiology
Publisher
Springer Science and Business Media LLC
Published
2022-10-20
Volume
21
Issue
4
Pages
248-259
ISSN
  • 1740-1526 (ISSN-L)
  • 1740-1534
DOI
10.1038/s41579-022-00796-9
OpenAlex
W4306878780
Cited by
447
References
138
Citations by year
2026: 146 · 2025: 157 · 2024: 93 · 2023: 48 · 2022: 3
FWCI
7.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Reviews Microbiology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders
  • Wellcome Trust (215599/Z/19/Z, 200208/A/15/Z, 101873/Z/13/Z)
  • Medical Research Council (MR/N006364, MR/N006364/2, MR/J008230/1, MR/M026663/2, MR/V033417/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
Keywords
fungal cell wall, chitin, β-glucan, cell wall architecture, cell wall mechanics, viscoelasticity, glycosylated proteins, cell wall hydrophobicity, cell adhesion, cell wall regulation, antifungal drug targets, fungal infection
MeSH terms
Antifungal Agents, Cell Wall, Chitin, Fungal Proteins, Glucans, beta-Glucans

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