Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia

ABSTRACT Hypoxia is the predominant condition that the human opportunistic fungus Candida albicans encounters in the majority of the colonized niches within the host. So far, the impact of such a condition on the overall metabolism of this important human-pathogenic yeast has not been investigated....

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Autores principales:	Anaïs Burgain, Faiza Tebbji, Inès Khemiri, Adnane Sellam
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida albicans hypoxia metabolomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/322c3535562349e2b1ad07414594f920
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spelling	oai:doaj.org-article:322c3535562349e2b1ad07414594f9202021-11-15T15:27:53ZMetabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia10.1128/mSphere.00913-192379-5042https://doaj.org/article/322c3535562349e2b1ad07414594f9202020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00913-19https://doaj.org/toc/2379-5042ABSTRACT Hypoxia is the predominant condition that the human opportunistic fungus Candida albicans encounters in the majority of the colonized niches within the host. So far, the impact of such a condition on the overall metabolism of this important human-pathogenic yeast has not been investigated. Here, we have undertaken a time-resolved metabolomics analysis to uncover the metabolic landscape of fungal cells experiencing hypoxia. Our data showed a dynamic reprogramming of many fundamental metabolic pathways, such as glycolysis, the pentose phosphate pathway, and different metabolic routes related to fungal cell wall biogenesis. The C. albicans lipidome was highly affected by oxygen depletion, with an increased level of free fatty acids and biochemical intermediates of membrane lipids, including phospholipids, lysophospholipids, sphingolipids, and mevalonate. The depletion of oxygen-dependent lipids such as ergosterol or phosphatidylcholine with longer and polyunsaturated lateral fatty acid chains was observed only at the later hypoxic time point (180 min). Transcriptomics data supported the main metabolic response to hypoxia when matched to our metabolomic profiles. The hypoxic metabolome reflected different physiological alterations of the cell wall and plasma membrane of C. albicans under an oxygen-limiting environment that were confirmed by different approaches. This study provided a framework for future in vivo investigations to examine relevant hypoxic metabolic trajectories in fungal virulence and fitness within the host. IMPORTANCE A critical aspect of cell fitness is the ability to sense and adapt to variations in oxygen levels in their local environment. Candida albicans is an opportunistic yeast that is the most prevalent human fungal pathogen. While hypoxia is the predominant condition that C. albicans encounters in most of its niches, its impact on fungal metabolism remains unexplored so far. Here, we provided a detailed landscape of the C. albicans metabolome that emphasized the importance of many metabolic routes for the adaptation of this yeast to oxygen depletion. The fungal hypoxic metabolome identified in this work provides a framework for future investigations to assess the contribution of relevant metabolic pathways in the fitness of C. albicans and other human eukaryotic pathogens with similar colonized human niches. As hypoxia is present at most of the fungal infection foci in the host, hypoxic metabolic pathways are thus an attractive target for antifungal therapy.Anaïs BurgainFaiza TebbjiInès KhemiriAdnane SellamAmerican Society for MicrobiologyarticleCandida albicanshypoxiametabolomicsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans hypoxia metabolomics Microbiology QR1-502
spellingShingle	Candida albicans hypoxia metabolomics Microbiology QR1-502 Anaïs Burgain Faiza Tebbji Inès Khemiri Adnane Sellam Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia
description	ABSTRACT Hypoxia is the predominant condition that the human opportunistic fungus Candida albicans encounters in the majority of the colonized niches within the host. So far, the impact of such a condition on the overall metabolism of this important human-pathogenic yeast has not been investigated. Here, we have undertaken a time-resolved metabolomics analysis to uncover the metabolic landscape of fungal cells experiencing hypoxia. Our data showed a dynamic reprogramming of many fundamental metabolic pathways, such as glycolysis, the pentose phosphate pathway, and different metabolic routes related to fungal cell wall biogenesis. The C. albicans lipidome was highly affected by oxygen depletion, with an increased level of free fatty acids and biochemical intermediates of membrane lipids, including phospholipids, lysophospholipids, sphingolipids, and mevalonate. The depletion of oxygen-dependent lipids such as ergosterol or phosphatidylcholine with longer and polyunsaturated lateral fatty acid chains was observed only at the later hypoxic time point (180 min). Transcriptomics data supported the main metabolic response to hypoxia when matched to our metabolomic profiles. The hypoxic metabolome reflected different physiological alterations of the cell wall and plasma membrane of C. albicans under an oxygen-limiting environment that were confirmed by different approaches. This study provided a framework for future in vivo investigations to examine relevant hypoxic metabolic trajectories in fungal virulence and fitness within the host. IMPORTANCE A critical aspect of cell fitness is the ability to sense and adapt to variations in oxygen levels in their local environment. Candida albicans is an opportunistic yeast that is the most prevalent human fungal pathogen. While hypoxia is the predominant condition that C. albicans encounters in most of its niches, its impact on fungal metabolism remains unexplored so far. Here, we provided a detailed landscape of the C. albicans metabolome that emphasized the importance of many metabolic routes for the adaptation of this yeast to oxygen depletion. The fungal hypoxic metabolome identified in this work provides a framework for future investigations to assess the contribution of relevant metabolic pathways in the fitness of C. albicans and other human eukaryotic pathogens with similar colonized human niches. As hypoxia is present at most of the fungal infection foci in the host, hypoxic metabolic pathways are thus an attractive target for antifungal therapy.
format	article
author	Anaïs Burgain Faiza Tebbji Inès Khemiri Adnane Sellam
author_facet	Anaïs Burgain Faiza Tebbji Inès Khemiri Adnane Sellam
author_sort	Anaïs Burgain
title	Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia
title_short	Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia
title_full	Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia
title_fullStr	Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia
title_full_unstemmed	Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia
title_sort	metabolic reprogramming in the opportunistic yeast <named-content content-type="genus-species">candida albicans</named-content> in response to hypoxia
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/322c3535562349e2b1ad07414594f920
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Metabolic Reprogramming in the Opportunistic Yeast <named-content content-type="genus-species">Candida albicans</named-content> in Response to Hypoxia

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