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Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization
Macrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such as Candida albicans developed strategies to evade the acidic environment. C. albicans is polymorphic and able to convert from yeast to hyphae, and this transition is...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134096/ https://www.ncbi.nlm.nih.gov/pubmed/30206168 http://dx.doi.org/10.1128/mBio.01226-18 |
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author | Westman, Johannes Moran, Gary Mogavero, Selene Hube, Bernhard Grinstein, Sergio |
author_facet | Westman, Johannes Moran, Gary Mogavero, Selene Hube, Bernhard Grinstein, Sergio |
author_sort | Westman, Johannes |
collection | PubMed |
description | Macrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such as Candida albicans developed strategies to evade the acidic environment. C. albicans is polymorphic and able to convert from yeast to hyphae, and this transition is required to subvert the microbicidal activity of the phagosome. However, the phagosomal lumen, which is acidic and nutrient deprived, is believed to inhibit the yeast-to-hypha transition. To account for this apparent paradox, it was recently proposed that C. albicans produces ammonia that alkalinizes the phagosome, thus facilitating yeast-to-hypha transition. We reexamined the mechanism underlying phagosomal alkalinization by applying dual-wavelength ratiometric pH measurements. The phagosomal membrane was found to be highly permeable to ammonia, which is therefore unlikely to account for the pH elevation. Instead, we find that yeast-to-hypha transition begins within acidic phagosomes and that alkalinization is a consequence of proton leakage induced by excessive membrane distension caused by the expanding hypha. |
format | Online Article Text |
id | pubmed-6134096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-61340962018-09-17 Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization Westman, Johannes Moran, Gary Mogavero, Selene Hube, Bernhard Grinstein, Sergio mBio Research Article Macrophages rely on phagosomal acidity to destroy engulfed microorganisms. To survive this hostile response, opportunistic fungi such as Candida albicans developed strategies to evade the acidic environment. C. albicans is polymorphic and able to convert from yeast to hyphae, and this transition is required to subvert the microbicidal activity of the phagosome. However, the phagosomal lumen, which is acidic and nutrient deprived, is believed to inhibit the yeast-to-hypha transition. To account for this apparent paradox, it was recently proposed that C. albicans produces ammonia that alkalinizes the phagosome, thus facilitating yeast-to-hypha transition. We reexamined the mechanism underlying phagosomal alkalinization by applying dual-wavelength ratiometric pH measurements. The phagosomal membrane was found to be highly permeable to ammonia, which is therefore unlikely to account for the pH elevation. Instead, we find that yeast-to-hypha transition begins within acidic phagosomes and that alkalinization is a consequence of proton leakage induced by excessive membrane distension caused by the expanding hypha. American Society for Microbiology 2018-09-11 /pmc/articles/PMC6134096/ /pubmed/30206168 http://dx.doi.org/10.1128/mBio.01226-18 Text en Copyright © 2018 Westman 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 Westman, Johannes Moran, Gary Mogavero, Selene Hube, Bernhard Grinstein, Sergio Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization |
title | Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization |
title_full | Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization |
title_fullStr | Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization |
title_full_unstemmed | Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization |
title_short | Candida albicans Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization |
title_sort | candida albicans hyphal expansion causes phagosomal membrane damage and luminal alkalinization |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134096/ https://www.ncbi.nlm.nih.gov/pubmed/30206168 http://dx.doi.org/10.1128/mBio.01226-18 |
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