<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization

ABSTRACT 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 trans...

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Autores principales:	Johannes Westman, Gary Moran, Selene Mogavero, Bernhard Hube, Sergio Grinstein
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Candida albicans candidalysin ECE1 alkalinization ammonia dual-wavelength radiometric imaging Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cf3cd67f412a44b6b25b392227b2031f
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spelling	oai:doaj.org-article:cf3cd67f412a44b6b25b392227b2031f2021-11-15T15:58:20Z<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization10.1128/mBio.01226-182150-7511https://doaj.org/article/cf3cd67f412a44b6b25b392227b2031f2018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01226-18https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE C. albicans is the most common cause of nosocomial fungal infection, and over 3 million people acquire life-threatening invasive fungal infections every year. Even if antifungal drugs exist, almost half of these patients will die. Despite this, fungi remain underestimated as pathogens. Our study uses quantitative biophysical approaches to demonstrate that yeast-to-hypha transition occurs within the nutrient-deprived, acidic phagosome and that alkalinization is a consequence, as opposed to the cause, of hyphal growth.Johannes WestmanGary MoranSelene MogaveroBernhard HubeSergio GrinsteinAmerican Society for MicrobiologyarticleCandida albicanscandidalysinECE1alkalinizationammoniadual-wavelength radiometric imagingMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans candidalysin ECE1 alkalinization ammonia dual-wavelength radiometric imaging Microbiology QR1-502
spellingShingle	Candida albicans candidalysin ECE1 alkalinization ammonia dual-wavelength radiometric imaging Microbiology QR1-502 Johannes Westman Gary Moran Selene Mogavero Bernhard Hube Sergio Grinstein <named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization
description	ABSTRACT 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. IMPORTANCE C. albicans is the most common cause of nosocomial fungal infection, and over 3 million people acquire life-threatening invasive fungal infections every year. Even if antifungal drugs exist, almost half of these patients will die. Despite this, fungi remain underestimated as pathogens. Our study uses quantitative biophysical approaches to demonstrate that yeast-to-hypha transition occurs within the nutrient-deprived, acidic phagosome and that alkalinization is a consequence, as opposed to the cause, of hyphal growth.
format	article
author	Johannes Westman Gary Moran Selene Mogavero Bernhard Hube Sergio Grinstein
author_facet	Johannes Westman Gary Moran Selene Mogavero Bernhard Hube Sergio Grinstein
author_sort	Johannes Westman
title	<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization
title_short	<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization
title_full	<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization
title_fullStr	<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization
title_full_unstemmed	<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization
title_sort	<named-content content-type="genus-species">candida albicans</named-content> hyphal expansion causes phagosomal membrane damage and luminal alkalinization
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/cf3cd67f412a44b6b25b392227b2031f
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<named-content content-type="genus-species">Candida albicans</named-content> Hyphal Expansion Causes Phagosomal Membrane Damage and Luminal Alkalinization

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