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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...

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Autores principales: O’Meara, Teresa R., Veri, Amanda O., Ketela, Troy, Jiang, Bo, Roemer, Terry, Cowen, Leah E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
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.
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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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