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Global analysis of fungal morphology exposes mechanisms of host cell escape
Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell deat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382923/ https://www.ncbi.nlm.nih.gov/pubmed/25824284 http://dx.doi.org/10.1038/ncomms7741 |
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author | O’Meara, Teresa R. Veri, Amanda O. Ketela, Troy Jiang, Bo Roemer, Terry Cowen, Leah E. |
author_facet | O’Meara, Teresa R. Veri, Amanda O. Ketela, Troy Jiang, Bo Roemer, Terry Cowen, Leah E. |
author_sort | O’Meara, Teresa R. |
collection | PubMed |
description | Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. |
format | Online Article Text |
id | pubmed-4382923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43829232015-04-17 Global analysis of fungal morphology exposes mechanisms of host cell escape O’Meara, Teresa R. Veri, Amanda O. Ketela, Troy Jiang, Bo Roemer, Terry Cowen, Leah E. Nat Commun Article Developmental transitions between single-cell yeast and multicellular filaments underpin virulence of diverse fungal pathogens. For the leading human fungal pathogen Candida albicans, filamentation is thought to be required for immune cell escape via induction of an inflammatory programmed cell death. Here we perform a genome-scale analysis of C. albicans morphogenesis and identify 102 negative morphogenetic regulators and 872 positive regulators, highlighting key roles for ergosterol biosynthesis and N-linked glycosylation. We demonstrate that C. albicans filamentation is not required for escape from host immune cells; instead, macrophage pyroptosis is driven by fungal cell-wall remodelling and exposure of glycosylated proteins in response to the macrophage phagosome. The capacity of killed, previously phagocytized cells to drive macrophage lysis is also observed with the distantly related fungal pathogen Cryptococcus neoformans. This study provides a global view of morphogenetic circuitry governing a key virulence trait, and illuminates a new mechanism by which fungi trigger host cell death. Nature Pub. Group 2015-03-31 /pmc/articles/PMC4382923/ /pubmed/25824284 http://dx.doi.org/10.1038/ncomms7741 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article O’Meara, Teresa R. Veri, Amanda O. Ketela, Troy Jiang, Bo Roemer, Terry Cowen, Leah E. Global analysis of fungal morphology exposes mechanisms of host cell escape |
title | Global analysis of fungal morphology exposes mechanisms of host cell escape |
title_full | Global analysis of fungal morphology exposes mechanisms of host cell escape |
title_fullStr | Global analysis of fungal morphology exposes mechanisms of host cell escape |
title_full_unstemmed | Global analysis of fungal morphology exposes mechanisms of host cell escape |
title_short | Global analysis of fungal morphology exposes mechanisms of host cell escape |
title_sort | global analysis of fungal morphology exposes mechanisms of host cell escape |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382923/ https://www.ncbi.nlm.nih.gov/pubmed/25824284 http://dx.doi.org/10.1038/ncomms7741 |
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