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Updated: May 16, 2025

CRISPR-mediated Genome Editing of the Human Fungal Pathogen Candida albicans
Published on: November 14, 2018
Regulation of meiotic gene expression is functional in the human fungal pathogen Candida glabrata
Natalia Klimova1, Cindy Ngov2, Frédéric Devaux3
1Department of Medicine, McGill University Health Centre, 1001 Boul. Décarie, Room E02.7212, Montréal, QC H4A 3J1, Canada.
Abstract:
The human fungal pathogen Candida glabrata is closely related to the budding yeast Saccharomyces cerevisiae. The sexual cycle in S. cerevisiae has been extensively characterized. Haploid cells 'a' and alpha secrete pheromones involved in mating of the opposite cell type leading to the formation of a diploid cell. Under harsh conditions, diploid cells undergo meiosis for the formation of four haploid spores. In C. glabrata, cells are also found as 'a' and alpha and this organism possesses most S. cerevisiae homologous genes involved in meiosis and mating. However, mating has never been observed in C. glabrata. In S. cerevisiae, the non-essential UME6 gene is involved in controlling the expression of meiotic genes. We have previously shown that Zcf11, a putative homolog of Ume6, is encoded by an essential gene but its function is unknown. Here, we show that the expression of UME6 in C. glabrata can partially complement a Zcf11 knock-down and that these factors recognize the same DNA sequence. Importantly, expression profiling using a Zcf11 knock-down strain revealed that this factor is a negative regulator of meiotic genes expression as well as some genes involved in mating. Thus, regulation of the expression of meiotic genes is functional in this organism reinforcing the view that C. glabrata may have a sexual cycle under specific conditions.
Insights
Candida glabrata Zcf11, a homolog of Saccharomyces cerevisiae UME6, negatively regulates genes for sexual reproduction. This suggests the fungal pathogen may possess a functional sexual cycle.
Area of Science:
- Microbiology
- Mycology
- Molecular Biology
Background:
- Candida glabrata, a human fungal pathogen, is closely related to Saccharomyces cerevisiae, a model organism with a well-characterized sexual cycle.
- Both species possess homologous genes for mating and meiosis, yet C. glabrata's sexual cycle remains unobserved.
- The UME6 gene in S. cerevisiae controls meiotic gene expression; its C. glabrata homolog, Zcf11, is essential but functionally uncharacterized.
Purpose of the Study:
- To investigate the function of Zcf11 in Candida glabrata.
- To determine if Zcf11 regulates genes involved in mating and meiosis.
- To explore the potential for a sexual cycle in C. glabrata.
Main Methods:
- Complementation assay: expressing S. cerevisiae UME6 in C. glabrata Zcf11 knock-down strains.
- DNA binding analysis to compare Zcf11 and Ume6 binding.
- Gene expression profiling of Zcf11 knock-down strains.
Main Results:
- S. cerevisiae UME6 partially complemented Zcf11 knock-down in C. glabrata.
- Zcf11 and Ume6 recognize the same DNA sequence.
- Zcf11 acts as a negative regulator of meiotic and mating genes in C. glabrata.
Conclusions:
- Zcf11 is a functional homolog of Ume6, regulating genes essential for sexual reproduction in C. glabrata.
- The regulatory mechanisms for meiotic gene expression are conserved and functional in C. glabrata.
- These findings support the hypothesis that C. glabrata may possess a cryptic or conditional sexual cycle.
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