Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells

ABSTRACT The white-opaque switch is a bistable, epigenetic transition affecting multiple traits in Candida albicans including mating, immunogenicity, and niche specificity. To compare how the two cell states respond to external cues, we examined the fitness, phenotypic switching, and filamentation p...

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Autores principales:	Iuliana V. Ene, Matthew B. Lohse, Adrian V. Vladu, Joachim Morschhäuser, Alexander D. Johnson, Richard J. Bennett
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d6317922d0f9460fb24513632b548dce
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spelling	oai:doaj.org-article:d6317922d0f9460fb24513632b548dce2021-11-15T15:50:15ZPhenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells10.1128/mBio.01269-162150-7511https://doaj.org/article/d6317922d0f9460fb24513632b548dce2016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01269-16https://doaj.org/toc/2150-7511ABSTRACT The white-opaque switch is a bistable, epigenetic transition affecting multiple traits in Candida albicans including mating, immunogenicity, and niche specificity. To compare how the two cell states respond to external cues, we examined the fitness, phenotypic switching, and filamentation properties of white cells and opaque cells under 1,440 different conditions at 25°C and 37°C. We demonstrate that white and opaque cells display striking differences in their integration of metabolic and thermal cues, so that the two states exhibit optimal fitness under distinct conditions. White cells were fitter than opaque cells under a wide range of environmental conditions, including growth at various pHs and in the presence of chemical stresses or antifungal drugs. This difference was exacerbated at 37°C, consistent with white cells being the default state of C. albicans in the mammalian host. In contrast, opaque cells showed greater fitness than white cells under select nutritional conditions, including growth on diverse peptides at 25°C. We further demonstrate that filamentation is significantly rewired between the two states, with white and opaque cells undergoing filamentous growth in response to distinct external cues. Genetic analysis was used to identify signaling pathways impacting the white-opaque transition both in vitro and in a murine model of commensal colonization, and three sugar sensing pathways are revealed as regulators of the switch. Together, these findings establish that white and opaque cells are programmed for differential integration of metabolic and thermal cues and that opaque cells represent a more metabolically specialized cell state than the default white state. IMPORTANCE Epigenetic transitions are an important mechanism by which microbes adapt to external stimuli. For Candida albicans, such transitions are crucial for adaptation to complex, fluctuating environments, and therefore contribute to its success as a human pathogen. The white-opaque switch modulates multiple C. albicans attributes, from sexual competency to niche specificity. Here, we demonstrate that metabolic circuits are extensively rewired between white and opaque states, so that the two cell types exhibit optimal fitness under different nutritional conditions and at different temperatures. We thereby establish that epigenetic events can profoundly alter the metabolism of fungal cells. We also demonstrate that epigenetic switching regulates filamentation and biofilm formation, two phenotypes closely associated with pathogenesis. These experiments reveal that white cells, considered the most clinically relevant form of C. albicans, are a “general-purpose” state suited to many environments, whereas opaque cells appear to represent a more metabolically specialized form of the species.Iuliana V. EneMatthew B. LohseAdrian V. VladuJoachim MorschhäuserAlexander D. JohnsonRichard J. BennettAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Iuliana V. Ene Matthew B. Lohse Adrian V. Vladu Joachim Morschhäuser Alexander D. Johnson Richard J. Bennett Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells
description	ABSTRACT The white-opaque switch is a bistable, epigenetic transition affecting multiple traits in Candida albicans including mating, immunogenicity, and niche specificity. To compare how the two cell states respond to external cues, we examined the fitness, phenotypic switching, and filamentation properties of white cells and opaque cells under 1,440 different conditions at 25°C and 37°C. We demonstrate that white and opaque cells display striking differences in their integration of metabolic and thermal cues, so that the two states exhibit optimal fitness under distinct conditions. White cells were fitter than opaque cells under a wide range of environmental conditions, including growth at various pHs and in the presence of chemical stresses or antifungal drugs. This difference was exacerbated at 37°C, consistent with white cells being the default state of C. albicans in the mammalian host. In contrast, opaque cells showed greater fitness than white cells under select nutritional conditions, including growth on diverse peptides at 25°C. We further demonstrate that filamentation is significantly rewired between the two states, with white and opaque cells undergoing filamentous growth in response to distinct external cues. Genetic analysis was used to identify signaling pathways impacting the white-opaque transition both in vitro and in a murine model of commensal colonization, and three sugar sensing pathways are revealed as regulators of the switch. Together, these findings establish that white and opaque cells are programmed for differential integration of metabolic and thermal cues and that opaque cells represent a more metabolically specialized cell state than the default white state. IMPORTANCE Epigenetic transitions are an important mechanism by which microbes adapt to external stimuli. For Candida albicans, such transitions are crucial for adaptation to complex, fluctuating environments, and therefore contribute to its success as a human pathogen. The white-opaque switch modulates multiple C. albicans attributes, from sexual competency to niche specificity. Here, we demonstrate that metabolic circuits are extensively rewired between white and opaque states, so that the two cell types exhibit optimal fitness under different nutritional conditions and at different temperatures. We thereby establish that epigenetic events can profoundly alter the metabolism of fungal cells. We also demonstrate that epigenetic switching regulates filamentation and biofilm formation, two phenotypes closely associated with pathogenesis. These experiments reveal that white cells, considered the most clinically relevant form of C. albicans, are a “general-purpose” state suited to many environments, whereas opaque cells appear to represent a more metabolically specialized form of the species.
format	article
author	Iuliana V. Ene Matthew B. Lohse Adrian V. Vladu Joachim Morschhäuser Alexander D. Johnson Richard J. Bennett
author_facet	Iuliana V. Ene Matthew B. Lohse Adrian V. Vladu Joachim Morschhäuser Alexander D. Johnson Richard J. Bennett
author_sort	Iuliana V. Ene
title	Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells
title_short	Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells
title_full	Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells
title_fullStr	Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells
title_full_unstemmed	Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells
title_sort	phenotypic profiling reveals that <named-content content-type="genus-species">candida albicans</named-content> opaque cells represent a metabolically specialized cell state compared to default white cells
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/d6317922d0f9460fb24513632b548dce
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Phenotypic Profiling Reveals that <named-content content-type="genus-species">Candida albicans</named-content> Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells

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