Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells

ABSTRACT It has been proposed that the ancestral fungus was mating competent and homothallic. However, many mating-competent fungi were initially classified as asexual because their mating capacity was hidden behind layers of regulation. For efficient in vitro mating, the essentially obligate diploi...

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Autores principales:	Yuan Sun, Christine Gadoury, Matthew P. Hirakawa, Richard J. Bennett, Doreen Harcus, Anne Marcil, Malcolm Whiteway
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Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
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spelling	oai:doaj.org-article:0e4ca5ae0b994fd68ebbb65f9e794fdc2021-11-15T15:41:41ZDeletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells10.1128/mBio.00465-162150-7511https://doaj.org/article/0e4ca5ae0b994fd68ebbb65f9e794fdc2016-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00465-16https://doaj.org/toc/2150-7511ABSTRACT It has been proposed that the ancestral fungus was mating competent and homothallic. However, many mating-competent fungi were initially classified as asexual because their mating capacity was hidden behind layers of regulation. For efficient in vitro mating, the essentially obligate diploid ascomycete pathogen Candida albicans has to change its mating type locus from heterozygous MTLa/α to homozygous MTLa/a or MTLα/α and then undergo an environmentally controlled epigenetic switch to the mating-competent opaque form. These requirements greatly reduce the potential for C. albicans mating. Deletion of the Yci1 domain gene OFR1 bypasses the need for C. albicans cells to change the mating type locus from heterozygous to homozygous prior to switching to the opaque form and mating and allows homothallic mating of MTL heterozygous strains. This bypass is carbon source dependent and does not occur when cells are grown on glucose. Transcriptional profiling of ofr1 mutant cells shows that in addition to regulating cell type and mating circuitry, Ofr1 is needed for proper regulation of histone and chitin biosynthesis gene expression. It appears that OFR1 is a key regulator in C. albicans and functions in part to maintain the cryptic mating phenotype of the pathogen. IMPORTANCE Candida albicans is a human fungal pathogen with a recently discovered, highly cryptic mating ability. For efficient mating, it has to lose heterozygosity at its mating type locus. Then, MTL homozygous strains can undergo an epigenetic switch to an elongated yeast state, termed the opaque form, and become mating competent. This infrequent two-step process greatly reduces the potential for mating; few strains are MTL homozygous, and the opaque state is unstable at the temperature of the mammalian host. C. albicans has a complex mechanism for mating that appears designed to ensure that mating is infrequent. Here, we have characterized a new gene, opaque-formation regulator 1 (OFR1). Deleting the OFR1 gene allows MTLa/α strains to mate efficiently with either mating type or even mate homothallically. It is possible that downregulating OFR1 in the host environment could allow mating in C. albicans by a route that does not involve MTL homozygosis.Yuan SunChristine GadouryMatthew P. HirakawaRichard J. BennettDoreen HarcusAnne MarcilMalcolm WhitewayAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 2 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Yuan Sun Christine Gadoury Matthew P. Hirakawa Richard J. Bennett Doreen Harcus Anne Marcil Malcolm Whiteway Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells
description	ABSTRACT It has been proposed that the ancestral fungus was mating competent and homothallic. However, many mating-competent fungi were initially classified as asexual because their mating capacity was hidden behind layers of regulation. For efficient in vitro mating, the essentially obligate diploid ascomycete pathogen Candida albicans has to change its mating type locus from heterozygous MTLa/α to homozygous MTLa/a or MTLα/α and then undergo an environmentally controlled epigenetic switch to the mating-competent opaque form. These requirements greatly reduce the potential for C. albicans mating. Deletion of the Yci1 domain gene OFR1 bypasses the need for C. albicans cells to change the mating type locus from heterozygous to homozygous prior to switching to the opaque form and mating and allows homothallic mating of MTL heterozygous strains. This bypass is carbon source dependent and does not occur when cells are grown on glucose. Transcriptional profiling of ofr1 mutant cells shows that in addition to regulating cell type and mating circuitry, Ofr1 is needed for proper regulation of histone and chitin biosynthesis gene expression. It appears that OFR1 is a key regulator in C. albicans and functions in part to maintain the cryptic mating phenotype of the pathogen. IMPORTANCE Candida albicans is a human fungal pathogen with a recently discovered, highly cryptic mating ability. For efficient mating, it has to lose heterozygosity at its mating type locus. Then, MTL homozygous strains can undergo an epigenetic switch to an elongated yeast state, termed the opaque form, and become mating competent. This infrequent two-step process greatly reduces the potential for mating; few strains are MTL homozygous, and the opaque state is unstable at the temperature of the mammalian host. C. albicans has a complex mechanism for mating that appears designed to ensure that mating is infrequent. Here, we have characterized a new gene, opaque-formation regulator 1 (OFR1). Deleting the OFR1 gene allows MTLa/α strains to mate efficiently with either mating type or even mate homothallically. It is possible that downregulating OFR1 in the host environment could allow mating in C. albicans by a route that does not involve MTL homozygosis.
format	article
author	Yuan Sun Christine Gadoury Matthew P. Hirakawa Richard J. Bennett Doreen Harcus Anne Marcil Malcolm Whiteway
author_facet	Yuan Sun Christine Gadoury Matthew P. Hirakawa Richard J. Bennett Doreen Harcus Anne Marcil Malcolm Whiteway
author_sort	Yuan Sun
title	Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells
title_short	Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells
title_full	Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells
title_fullStr	Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells
title_full_unstemmed	Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells
title_sort	deletion of a yci1 domain protein of <named-content content-type="genus-species">candida albicans</named-content> allows homothallic mating in <italic toggle="yes">mtl</italic> heterozygous cells
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/0e4ca5ae0b994fd68ebbb65f9e794fdc
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Deletion of a Yci1 Domain Protein of <named-content content-type="genus-species">Candida albicans</named-content> Allows Homothallic Mating in <italic toggle="yes">MTL</italic> Heterozygous Cells

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