Deletion of a Yci1 Domain Protein of Candida albicans Allows Homothallic Mating in MTL Heterozygous Cells.

Yuan Sun,Christine Gadoury,Doreen Harcus,Matthew P Hirakawa,Malcolm Whiteway,Richard J Bennett,Anne Marcil,Judith Berman

doi:10.1128/mbio.00465-16

Yuan Sun, Christine Gadoury + Show 6 more

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https://doi.org/10.1128/mbio.00465-16

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Abstract

ABSTRACTIt 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.

Highlights

It has been proposed that the ancestral fungus was mating competent and homothallic
In the fungal pathogen C. albicans, the white-opaque transition is typically restricted to cells homozygous for the MTL locus, as the a1-␣2 repressor prevents expression of the transcription factor WOR1 required for formation of the opaque state [13,14,15]
We screened for additional genes involved in white-opaque switching using a mutant library, GRACE version 1.0, containing approximately 900 MTL heterozygous strains disrupted for nonessential genes to identify mutants that were capable of undergoing white-opaque switching when cells were cultured on GlcNAc medium at room temperature (RT)

Summary

Introduction

It has been proposed that the ancestral fungus was mating competent and homothallic. many matingcompetent 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/␣ to homozygous MTLa/a or MTL␣/␣ and 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 Yci 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. WOR1 is in a bistable expression loop that is driven by feedback regulation; the positive feedback loop makes opaque cells stable after several cell divisions and the negative feedback loop makes the white-to-opaque transition reversible due to the influence of environmental factors [13,14,15]

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