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Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation
Candida albicans exists as a commensal of mucosal surfaces and the gastrointestinal tract without causing pathology. However, this fungus is also a common cause of mucosal and systemic infections when antifungal immune defenses become compromised. The activation of antifungal host defenses depends o...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9765427/ https://www.ncbi.nlm.nih.gov/pubmed/36218369 http://dx.doi.org/10.1128/mbio.02605-22 |
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author | de Assis, Leandro José Bain, Judith M. Liddle, Corin Leaves, Ian Hacker, Christian Peres da Silva, Roberta Yuecel, Raif Bebes, Attila Stead, David Childers, Delma S. Pradhan, Arnab Mackenzie, Kevin Lagree, Katherine Larcombe, Daniel E. Ma, Qinxi Avelar, Gabriela Mol Netea, Mihai G. Erwig, Lars P. Mitchell, Aaron P. Brown, Gordon D. Gow, Neil A. R. Brown, Alistair J. P. |
author_facet | de Assis, Leandro José Bain, Judith M. Liddle, Corin Leaves, Ian Hacker, Christian Peres da Silva, Roberta Yuecel, Raif Bebes, Attila Stead, David Childers, Delma S. Pradhan, Arnab Mackenzie, Kevin Lagree, Katherine Larcombe, Daniel E. Ma, Qinxi Avelar, Gabriela Mol Netea, Mihai G. Erwig, Lars P. Mitchell, Aaron P. Brown, Gordon D. Gow, Neil A. R. Brown, Alistair J. P. |
author_sort | de Assis, Leandro José |
collection | PubMed |
description | Candida albicans exists as a commensal of mucosal surfaces and the gastrointestinal tract without causing pathology. However, this fungus is also a common cause of mucosal and systemic infections when antifungal immune defenses become compromised. The activation of antifungal host defenses depends on the recognition of fungal pathogen-associated molecular patterns (PAMPs), such as β-1,3-glucan. In C. albicans, most β-1,3-glucan is present in the inner cell wall, concealed by the outer mannan layer, but some β-1,3-glucan becomes exposed at the cell surface. In response to host signals, such as lactate, C. albicans induces the Xog1 exoglucanase, which shaves exposed β-1,3-glucan from the cell surface, thereby reducing phagocytic recognition. We show here that β-1,3-glucan is exposed at bud scars and punctate foci on the lateral wall of yeast cells, that this exposed β-1,3-glucan is targeted during phagocytic attack, and that lactate-induced masking reduces β-1,3-glucan exposure at bud scars and at punctate foci. β-1,3-Glucan masking depends upon protein kinase A (PKA) signaling. We reveal that inactivating PKA, or its conserved downstream effectors, Sin3 and Mig1/Mig2, affects the amounts of the Xog1 and Eng1 glucanases in the C. albicans secretome and modulates β-1,3-glucan exposure. Furthermore, perturbing PKA, Sin3, or Mig1/Mig2 attenuates the virulence of lactate-exposed C. albicans cells in Galleria. Taken together, the data are consistent with the idea that β-1,3-glucan masking contributes to Candida pathogenicity. |
format | Online Article Text |
id | pubmed-9765427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-97654272022-12-21 Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation de Assis, Leandro José Bain, Judith M. Liddle, Corin Leaves, Ian Hacker, Christian Peres da Silva, Roberta Yuecel, Raif Bebes, Attila Stead, David Childers, Delma S. Pradhan, Arnab Mackenzie, Kevin Lagree, Katherine Larcombe, Daniel E. Ma, Qinxi Avelar, Gabriela Mol Netea, Mihai G. Erwig, Lars P. Mitchell, Aaron P. Brown, Gordon D. Gow, Neil A. R. Brown, Alistair J. P. mBio Research Article Candida albicans exists as a commensal of mucosal surfaces and the gastrointestinal tract without causing pathology. However, this fungus is also a common cause of mucosal and systemic infections when antifungal immune defenses become compromised. The activation of antifungal host defenses depends on the recognition of fungal pathogen-associated molecular patterns (PAMPs), such as β-1,3-glucan. In C. albicans, most β-1,3-glucan is present in the inner cell wall, concealed by the outer mannan layer, but some β-1,3-glucan becomes exposed at the cell surface. In response to host signals, such as lactate, C. albicans induces the Xog1 exoglucanase, which shaves exposed β-1,3-glucan from the cell surface, thereby reducing phagocytic recognition. We show here that β-1,3-glucan is exposed at bud scars and punctate foci on the lateral wall of yeast cells, that this exposed β-1,3-glucan is targeted during phagocytic attack, and that lactate-induced masking reduces β-1,3-glucan exposure at bud scars and at punctate foci. β-1,3-Glucan masking depends upon protein kinase A (PKA) signaling. We reveal that inactivating PKA, or its conserved downstream effectors, Sin3 and Mig1/Mig2, affects the amounts of the Xog1 and Eng1 glucanases in the C. albicans secretome and modulates β-1,3-glucan exposure. Furthermore, perturbing PKA, Sin3, or Mig1/Mig2 attenuates the virulence of lactate-exposed C. albicans cells in Galleria. Taken together, the data are consistent with the idea that β-1,3-glucan masking contributes to Candida pathogenicity. American Society for Microbiology 2022-10-11 /pmc/articles/PMC9765427/ /pubmed/36218369 http://dx.doi.org/10.1128/mbio.02605-22 Text en Copyright © 2022 de Assis et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article de Assis, Leandro José Bain, Judith M. Liddle, Corin Leaves, Ian Hacker, Christian Peres da Silva, Roberta Yuecel, Raif Bebes, Attila Stead, David Childers, Delma S. Pradhan, Arnab Mackenzie, Kevin Lagree, Katherine Larcombe, Daniel E. Ma, Qinxi Avelar, Gabriela Mol Netea, Mihai G. Erwig, Lars P. Mitchell, Aaron P. Brown, Gordon D. Gow, Neil A. R. Brown, Alistair J. P. Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation |
title | Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation |
title_full | Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation |
title_fullStr | Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation |
title_full_unstemmed | Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation |
title_short | Nature of β-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation |
title_sort | nature of β-1,3-glucan-exposing features on candida albicans cell wall and their modulation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9765427/ https://www.ncbi.nlm.nih.gov/pubmed/36218369 http://dx.doi.org/10.1128/mbio.02605-22 |
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