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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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Research works printed but not linked: 110

  1. Verstrepen, K. J., Reynolds, T. B. & Fink, G. R. Origins of variation in the fungal cell surface. Nat. Rev. Microbiol. 2, 533–540 (2004). · DOI
  2. de Groot, P. W. et al. A genomic approach for the identification and classification of genes involved in cell wall formation and its regulation in Saccharomyces cerevisiae. Comp. Funct. Genomics 2, 124–142 (2001). · DOI
  3. Polizeli, M. L., Pietro, R. C., Jorge, J. A. & Terenzi, H. F. Effects of cell wall deficiency on the synthesis of polysaccharide-degrading exoenzymes: a study on mycelial and wall-less phenotypes of the fz; sg; os-1 (‘slime’) triple mutant of Neurospora crassa. J. Gen. Microbiol. 136, 1463–1468 (1990). · DOI
  4. Ene, I. V. et al. Cell wall remodeling enzymes modulate fungal cell wall elasticity and osmotic stress resistance. mBio 6, e00986 (2015). · DOI
  5. Money, N. P. & Fischer, M. W. F. in Plant Relationships Vol. 5 (ed. Deising, H. B.) 115–133 (Springer, 2009).
  6. Davì, V. et al. Mechanosensation dynamically coordinates polar growth and cell wall assembly to promote cell survival. Dev. Cell 45, 170–182.e7 (2018). This report demonstrates that cell wall thickness fluctuates during cell growth and is regulated by a mechanosensitive homeostatic mechanism. · DOI
  7. Veneault-Fourrey, C., Barooah, M., Egan, M., Wakley, G. & Talbot, N. J. Autophagic fungal cell death is necessary for infection by the rice blast fungus. Science 312, 580–583 (2006). · DOI
  8. Howard, R. J., Ferrari, M. A., Roach, D. H. & Money, N. P. Penetration of hard substrates by a fungus employing enormous turgor pressures. Proc. Natl Acad. Sci. USA 88, 11281–11284 (1991). · DOI
  9. Talbot, N. J. Appressoria. Curr. Biol. 29, R144–R146 (2019). · DOI
  10. Berger, B. W. & Sallada, N. D. Hydrophobins: multifunctional biosurfactants for interface engineering. J. Biol. Eng. 13, 10 (2019). · DOI
  11. Wösten, H. A. B. Hydrophobins: multipurpose proteins. Annu. Rev. Microbiol. 55, 625–646 (2001). · DOI
  12. Winandy, L., Schlebusch, O. & Fischer, R. Fungal hydrophobins render stones impermeable for water but keep them permeable for vapor. Sci. Rep. 9, 6264 (2019). This publication explores the biophysical properties of fungal cell wall hydrophobin layers and shows that they have remarkable breathable yet waterproof properties. · DOI
  13. Nehls, U. & Dietz, S. Fungal aquaporins: cellular functions and ecophysiological perspectives. Appl. Microbiol. Biotechnol. 98, 8835–8851 (2014). · DOI
  14. Casadevall, A. et al. The capsule of Cryptococcus neoformans. Virulence 10, 822–831 (2019). · DOI
  15. Tlalka, M., Fricker, M. & Watkinson, S. Imaging of long-distance α-aminoisobutyric acid translocation dynamics during resource capture by Serpula lacrymans. Appl. Environ. Microbiol. 74, 2700–2708 (2008). · DOI
  16. Aguilar-Trigueros, C. A., Boddy, L., Rillig, M. C. & Fricker, M. D. Network traits predict ecological strategies in fungi. ISME Commun. 2, 2 (2022). · DOI
  17. Lew, R. R. How does a hypha grow? The biophysics of pressurized growth in fungi. Nat. Rev. Microbiol. 9, 509–518 (2011). · DOI
  18. Read, N. D. in Oxford Textbook of Medical Mycology Ch. 4 (eds Kibbler, K. C. et al.) 23–34 (Oxford Univ. Press, 2018). · DOI
  19. Grün, C. H. et al. The structure of cell wall α-glucan from fission yeast. Glycobiology 15, 245–257 (2005). · DOI
  20. Ma, L. et al. Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts. Nat. Commun. 7, 10740 (2016). · DOI
  21. Muzzarelli, C. J. & Gooday, G. W. (eds). Chitin in Nature and Technology (Springer, 1986). · DOI
  22. Kanagawa, M. et al. Structural insights into recognition of triple-helical β-glucans by an insect fungal receptor. J. Biol. Chem. 286, 29158–29165 (2011). · DOI
  23. Liu, Y. et al. Triple helix conformation of β-d-glucan from Ganoderma lucidum and effect of molecular weight on its immunostimulatory activity. Int. J. Biol. Macromol. 114, 1064–1070 (2018). · DOI
  24. Fernando, L. D. et al. Structural polymorphism of chitin and chitosan in fungal cell walls from solid-state NMR and principal component analysis. Front. Mol. Biosci. 8, 727053 (2021). · DOI
  25. Latgé, J. P. & Wang, T. Modern biophysics redefines our understanding of fungal cell wall structure, complexity, and dynamics. mBio 13, e0114522 (2022). · DOI · Paper page
  26. Orlean, P. & Funai, D. Priming and elongation of chitin chains: implications for chitin synthase mechanism. Cell Surf. 5, 100017 (2019). · DOI
  27. da Silva Dantas, A. et al. Crosstalk between the calcineurin and cell wall integrity pathways prevents chitin overexpression in Candida albicans. J. Cell Sci. 134, jcs258889 (2021). · DOI · Paper page
  28. Gow, N. A. R. & Gooday, G. W. Ultrastructure of chitin in hyphae of Candida albicans and other dimorphic and mycelial fungi. Protoplasma 115, 52–58 (1983). · DOI
  29. Vermeulen, C. A. & Wessels, J. G. H. Ultrastructural differences between wall apices of growing and non-growing hyphae of Schizophyllum commune. Protoplasma 120, 123–131 (1984). · DOI
  30. Vermeulen, C. A. & Wessels, J. G. Chitin biosynthesis by a fungal membrane preparation. Evidence for a transient non-crystalline state of chitin. Eur. J. Biochem. 158, 411–415 (1986). · DOI
  31. Lenardon, M. D., Sood, P., Dorfmueller, H. C., Brown, A. J. P. & Gow, N. A. R. Scalar nanostructure of the Candida albicans cell wall; a molecular, cellular and ultrastructural analysis and interpretation. Cell Surf. 6, 100047 (2020). This publication provides the first to-scale model of the C. albicans cell wall and includes a menu of icons which can be used to construct other bespoke cell wall models. · DOI · Paper page
  32. Kang, X. et al. Molecular architecture of fungal cell walls revealed by solid-state NMR. Nat. Commun. 9, 2747 (2018). This report utilizes solid-state nuclear magnetic resonance to demonstrate that chitin and α-1,3-glucan in the Aspergillus cell wall forms a hydrophobic scaffold which is surrounded by β-glucans and capped by glycoproteins and α-1,3-glucan. · DOI · Paper page
  33. Krol, P. Synthesis methods, chemical structures and phase structures of linear polyurethanes. Properties and applications of linear polyurethanes in polyurethane elastomers, copolymers and ionomers. Prog. Mater. Sci. 52, 915–1015 (2007). · DOI
  34. Bates, S. et al. Outer chain N-glycans are required for cell wall integrity and virulence of Candida albicans. J. Biol. Chem. 281, 90–98 (2006). · DOI
  35. Walker, L. et al. The viscoelastic properties of the fungal cell wall allow traffic of AmBisome as intact liposome vesicles. mBio 9, e02383-17 (2018). This study demonstrates that intact AmBisome vesicles can carry non-elastic gold particle cargoes through the fungal cell wall. · DOI
  36. Ballou, E. R. et al. Lactate signalling regulates fungal β-glucan masking and immune evasion. Nat. Microbiol. 2, 16238 (2016). This study makes key observations that Candida cells ‘mask’ β-1,3-glucan when grown on lactate, demonstrating that metabolic adaptability makes Candida cells an immunological moving target. · DOI · Paper page
  37. Pradhan, A. et al. Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion. Nat. Commun. 10, 5315 (2019). · DOI · Paper page
  38. Lopes-Bezerra, L. M. et al. Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers. PLoS Negl. Trop. Dis. 12, e0006169 (2018). · DOI
  39. Hobson, R. P. et al. Loss of cell wall mannosylphosphate in Candida albicans does not influence macrophage recognition. J. Biol. Chem. 279, 39628–39635 (2004). · DOI
  40. Trinel, P. A. et al. Candida albicans serotype B strains synthesize a serotype-specific phospholipomannan overexpressing a β-1,2-linked mannotriose. Mol. Microbiol. 58, 984–998 (2005). · DOI
  41. Singleton, D. R., Masuoka, J. & Hazen, K. C. Surface hydrophobicity changes of two Candida albicans serotype B mnn4delta mutants. Eukaryot. Cell 4, 639–648 (2005). · DOI
  42. Silva-Dias, A. et al. Adhesion, biofilm formation, cell surface hydrophobicity, and antifungal planktonic susceptibility: relationship among Candida spp. Front. Microbiol. 6, 205 (2015). · DOI
  43. Wessels, J. G. H. Hydrophobins, unique fungal proteins. Mycologist 14, 153–159 (2000). · DOI
  44. Aimanianda, V. et al. Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature 460, 1117–1121 (2009). · DOI · Paper page
  45. Carrion, S. J. et al. The RodA hydrophobin on Aspergillus fumigatus spores masks dectin-1- and dectin-2-dependent responses and enhances fungal survival in vivo. J. Immunol. 191, 2581–2588 (2013). · DOI
  46. Willaert, R. G. Adhesins of yeasts: protein structure and interactions. J. Fungi 4, 119 (2018). · DOI
  47. Staab, J. F., Bradway, S. D., Fidel, P. L. & Sundstrom, P. Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283, 1535–1538 (1999). · DOI
  48. Vendele, I. et al. Mannan detecting C-type lectin receptor probes recognise immune epitopes with diverse chemical, spatial and phylogenetic heterogeneity in fungal cell walls. PLoS Pathog. 16, e1007927 (2020). · DOI
  49. Kumar, R., Breindel, C., Saraswat, D., Cullen, P. J. & Edgerton, M. Candida albicans Sap6 amyloid regions function in cellular aggregation and zinc binding, and contribute to zinc acquisition. Sci. Rep. 7, 2908 (2017). · DOI
  50. Lipke, P. N., Klotz, S. A., Dufrene, Y. F., Jackson, D. N. & Garcia-Sherman, M. C. Amyloid-like β-aggregates as force-sensitive switches in fungal biofilms and infections. Microbiol. Mol. Biol. Rev. 82, e00035-17 (2018). · DOI
  51. Speth, C., Rambach, G., Lass-Flörl, C., Howell, P. L. & Sheppard, D. C. Galactosaminogalactan (GAG) and its multiple roles in Aspergillus pathogenesis. Virulence 10, 976–983 (2019). · DOI
  52. Gravelat, F. N. et al. Aspergillus galactosaminogalactan mediates adherence to host constituents and conceals hyphal β-glucan from the immune system. PLoS Pathog. 9, e1003575 (2013). This paper demonstrates that an epimerase is required for GAG synthesis which mediates adhesion of Aspergillus to a range of surfaces and is essential for virulence. · DOI · Paper page
  53. Nosanchuk, J. D., Stark, R. E. & Casadevall, A. Fungal melanin: what do we know about structure? Front. Microbiol. 6, 1463 (2015). · DOI · Paper page
  54. Liu, S., Youngchim, S., Zamith-Miranda, D. & Nosanchuk, J. D. Fungal melanin and the mammalian immune system. J. Fungi 7, 264 (2021). · DOI
  55. Casadevall, A., Cordero, R. J. B., Bryan, R., Nosanchuk, J. & Dadachova, E. Melanin, radiation, and energy transduction in fungi. Microbiol. Spectr. 5, 5.2.05 (2017). This work proposes that fungal cell wall melanin can harness electromagnetic radiation as an energy source to promote survival. · DOI · Paper page
  56. De Nobel, J. G., Dijkers, C., Hooijberg, E. & Klis, F. M. Increased cell wall porosity in Saccharomyces cerevisiae after treatment with dithiothreitol or EDTA. Microbiology 135, 2077–2084 (1989). · DOI
  57. Yadav, B. et al. Differences in fungal immune recognition by monocytes and macrophages: N-mannan can be a shield or activator of immune recognition. Cell Surf. 6, 100042 (2020). · DOI
  58. Nazik, H. et al. Pseudomonas phage inhibition of Candida albicans. Microbiology 163, 1568–1577 (2017). · DOI
  59. Nuss, D. L. Hypovirulence: mycoviruses at the fungal–plant interface. Nat. Rev. Microbiol. 3, 632–642 (2005). · DOI
  60. Kim, Y. & Mylonakis, E. Killing of Candida albicans filaments by Salmonella enterica serovar Typhimurium is mediated by sopB effectors, parts of a type III secretion system. Eukaryot. Cell 10, 782–790 (2011). · DOI
  61. Trunk, K. et al. The type VI secretion system deploys antifungal effectors against microbial competitors. Nat. Microbiol. 3, 920–931 (2018). · DOI
  62. Cuskin, F. et al. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism. Nature 517, 165–169 (2015). · DOI
  63. Zhao, K. et al. Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling. Commun. Biol. 2, 305 (2019). · DOI
  64. Dawson, C. S. et al. Protein markers for Candida albicans EVs include claudin-like Sur7 family proteins. J. Extracell. Vesicles 9, 1750810 (2020). · DOI
  65. Zhao, M. et al. Turbinmicin inhibits Candida biofilm growth by disrupting fungal vesicle-mediated trafficking. J. Clin. Invest. 131, e145123 (2021). · DOI · Paper page
  66. He, B. et al. RNA-binding proteins contribute to small RNA loading in plant extracellular vesicles. Nat. Plants 7, 342–352 (2021). · DOI
  67. Sorgo, A. G., Heilmann, C. J., Brul, S., de Koster, C. G. & Klis, F. M. Beyond the wall: Candida albicans secret(e)s to survive. FEMS Microbiol. Lett. 338, 10–17 (2013). · DOI
  68. Kenno, S. et al. Candida albicans factor H binding molecule Hgt1p — a low glucose-induced transmembrane protein is trafficked to the cell wall and impairs phagocytosis and killing by human neutrophils. Front. Microbiol. 9, 3319 (2019). · DOI
  69. Urban, C. et al. The moonlighting protein Tsa1p is implicated in oxidative stress response and in cell wall biogenesis in Candida albicans. Mol. Microbiol. 57, 1318–1341 (2005). · DOI
  70. Satala, D., Karkowska-Kuleta, J., Zelazna, A., Rapala-Kozik, M. & Kozik, A. Moonlighting proteins at the Candidal cell surface. Microorganisms 8, 1046 (2020). · DOI
  71. Gow, N. A. R., Latge, J. P. & Munro, C. A. The fungal cell wall: structure, biosynthesis, and function. Microbiol. Spectr. 5, 5.3.01 (2017). · DOI · Paper page
  72. Riquelme, M. et al. Fungal morphogenesis, from the polarized growth of hyphae to complex reproduction and infection structures. Microbiol. Mol. Biol. Rev. 82, e00068-17 (2018). · DOI
  73. Arkowitz, R. A. & Bassilana, M. Recent advances in understanding Candida albicans hyphal growth. F1000Res 8, 700 (2019). · DOI · Paper page
  74. Schuster, M. et al. Co-delivery of cell-wall-forming enzymes in the same vesicle for coordinated fungal cell wall formation. Nat. Microbiol. 1, 16149 (2016). This study shows that the Ustilago class V and class VII chitin synthases (chitin synthases with an N-terminal myosin motor-like domain) and β-1,3-glucan synthases are transported and co-secreted in the same vesicles and that the myosin motor-like domains play a key role in the secretory process. · DOI
  75. Klis, F. M., de Groot, P. & Hellingwerf, K. Molecular organization of the cell wall of Candida albicans. Med. Mycol. 39, 1–8 (2001). · DOI · Paper page
  76. Garcia-Rubio, R., de Oliveira, H. C., Rivera, J. & Trevijano-Contador, N. The fungal cell wall: Candida, Cryptococcus, and Aspergillus species. Front. Microbiol. 10, 2993 (2019). · DOI · Paper page
  77. Yoshimi, A., Miyazawa, K. & Abe, K. Cell wall structure and biogenesis in Aspergillus species. Biosci. Biotechnol. Biochem. 80, 1700–1711 (2016). · DOI
  78. Knafler, H. C. et al. AP-2-dependent endocytic recycling of the chitin synthase Chs3 regulates polarized growth in Candida albicans. mBio 10, e02421-18 (2019). · DOI
  79. Munro, C. A. et al. The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans. Mol. Microbiol. 63, 1399–1413 (2007). · DOI · Paper page
  80. Dichtl, K., Samantaray, S. & Wagener, J. Cell wall integrity signalling in human pathogenic fungi. Cell. Microbiol. 18, 1228–1238 (2016). · DOI · Paper page
  81. Ibe, C. & Munro, C. A. Fungal cell wall: an underexploited target for antifungal therapies. PLoS Pathog. 17, e1009470 (2021). · DOI
  82. González-Rubio, G., Fernández-Acero, T., Martín, H. & Molina, M. Mitogen-activated protein kinase phosphatases (MKPs) in fungal signaling: conservation, function, and regulation. Int. J. Mol. Sci. 20, 1709 (2019). · DOI
  83. Geißel, B. et al. Azole-induced cell wall carbohydrate patches kill Aspergillus fumigatus. Nat. Commun. 9, 3098 (2018). This work shows that azole antifungals lead to the formation of carbohydrate patches that penetrate and rupture the cell membrane, leading to cidal effects. · DOI · Paper page
  84. Erwig, L. P. & Gow, N. A. R. Interactions of fungal pathogens with phagocytes. Nat. Rev. Microbiol. 14, 163–176 (2016). · DOI · Paper page
  85. Brown, G. D., Willment, J. A. & Whitehead, L. C-Type lectins in immunity and homeostasis. Nat. Rev. Immunol. 18, 374–389 (2018). · DOI
  86. Casadevall, A. Immunity to invasive fungal diseases. Annu. Rev. Immunol. 40, 121–141 (2022). · DOI
  87. Rappleye, C. A. & Goldman, W. E. Fungal stealth technology. Trends Immunol. 29, 18–24 (2008). · DOI
  88. Graus, M. S. et al. Mannan molecular substructures control nanoscale glucan exposure in. Candida. Cell Rep. 24, 2432–2442 (2018). · DOI
  89. Wheeler, R. T. & Fink, G. R. A drug-sensitive genetic network masks fungi from the immune system. PLoS Pathog. 2, e35 (2006). · DOI
  90. Cottier, F. et al. Remasking of Candida albicans β-glucan in response to environmental pH is regulated by quorum sensing. mBio 10, e02347-19 (2019). · DOI
  91. Chen, T., Wagner, A. S. & Reynolds, T. B. When is it appropriate to take off the mask? Signaling pathways that regulate β(1,3)-glucan exposure in Candida albicans. Front. Fungal Biol. 3, 842501 (2022). · DOI
  92. Lopes, J. P. et al. Evasion of immune surveillance in low oxygen environments enhances Candida albicans virulence. mBio 9, e02120-18 (2018). · DOI · Paper page
  93. Childers, D. S. et al. Epitope shaving promotes fungal immune evasion. mBio 11, e00984-20 (2020). This work shows that the removal of superficial strands of β-1,3-glucan from the Candida cell surface by the β-glucanase Xog1 contributes to the immunological disguise of cells by preventing glucan recognition by the dectin 1 receptor. · DOI
  94. Hole, C. R., Lam, W. C., Upadhya, R. & Lodge, J. K. Cryptococcus neoformans chitin synthase 3 plays a critical role in dampening host inflammatory responses. mBio 11, e03373-19 (2020). · DOI
  95. Lam, W. C. et al. Chitosan biosynthesis and virulence in the human fungal pathogen Cryptococcus gattii. mSphere 4, e00644-19 (2019). · DOI
  96. Davis, M. R., Donnelley, M. A. & Thompson, G. R. Ibrexafungerp: a novel oral glucan synthase inhibitor. Med. Mycol. 58, 579–592 (2020). · DOI · Paper page
  97. Pfaller, M. A., Huband, M. D., Flamm, R. K., Bien, P. A. & Castanheira, M. Antimicrobial activity of manogepix, a first-in-class antifungal, and comparator agents tested against contemporary invasive fungal isolates from an international surveillance programme (2018–2019). J. Glob. Antimicrob. Resist. 26, 117–127 (2021). · DOI
  98. Steinbach, W. J. et al. Calcineurin inhibition or mutation enhances cell wall inhibitors against Aspergillus fumigatus. Antimicrob. Agents Chemother. 51, 2979–2981 (2007). · DOI · Paper page
  99. Hussain, K. K. et al. Biosensors and diagnostics for fungal detection. J. Fungi 6, 349 (2020). · DOI
  100. Edwards, J. E. Jr. et al. A fungal immunotherapeutic vaccine (NDV-3A) for treatment of recurrent vulvovaginal candidiasis — a phase 2 randomized, double-blind, placebo-controlled trial. Clin. Infect. Dis. 66, 1928–1936 (2018). · DOI · Paper page
  101. Datta, K., Lees, A. & Pirofski, L. A. Therapeutic efficacy of a conjugate vaccine containing a peptide mimotope of cryptococcal capsular polysaccharide glucuronoxylomannan. Clin. Vaccin. Immunol. 15, 1176–1187 (2008). · DOI
  102. Devi, S. J. Preclinical efficacy of a glucuronoxylomannan–tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model. Vaccine 14, 841–844 (1996). · DOI
  103. Meagher, R. B., Lewis, Z. A., Ambati, S. & Lin, X. Aiming for a bull’s-eye: targeting antifungals to fungi with dectin-decorated liposomes. PLoS Pathog. 17, e1009699 (2021). · DOI
  104. Rudkin, F. M. et al. Single human B cell-derived monoclonal anti-Candida antibodies enhance phagocytosis and protect against disseminated candidiasis. Nat. Commun. 9, 5288 (2018). · DOI
  105. Palliyil, S. et al. Monoclonal antibodies targeting surface-exposed epitopes of Candida albicans cell wall proteins confer in vivo protection in an infection model. Antimicrob. Agents Chemother. 66, e0195721 (2022). · DOI
  106. De Nobel, J. G., Klis, F. M., Munnik, T., Priem, J. & Van Den Ende, H. An assay of relative cell wall porosity in Saccharomyces cerevisiae, Kluyveromyces lactis and Schizosaccharomyces pombe. Yeast 6, 483–490 (1990). · DOI
  107. Bleackley, M. R., Dawson, C. S. & Anderson, M. A. Fungal extracellular vesicles with a focus on proteomic analysis. Proteomics 19, e1800232 (2019). · DOI
  108. Casadevall, A., Nosanchuk, J. D., Williamson, P. & Rodrigues, M. L. Vesicular transport across the fungal cell wall. Trends Microbiol. 17, 158–162 (2009). · DOI
  109. Rodrigues, M. L. & Casadevall, A. A two-way road: novel roles for fungal extracellular vesicles. Mol. Microbiol. 110, 11–15 (2018). · DOI
  110. Zand Karimi, H. et al. Arabidopsis apoplastic fluid contains sRNA– and circular RNA–protein complexes that are located outside extracellular vesicles. Plant Cell 34, 1863–1881 (2022). · DOI

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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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