Transcriptional regulation of carbohydrate metabolism in the human pathogen Candida albicans
Open accessAbstract
Glycolysis is a metabolic pathway that is central to the assimilation of carbon for either respiration or fermentation and therefore is critical for the growth of all organisms. Consequently, glycolytic transcriptional regulation is important for the metabolic flexibility of pathogens in their attempts to colonize diverse niches. We investigated the transcriptional control of carbohydrate metabolism in the human fungal pathogen Candida albicans and identified two factors, Tye7p and Gal4p, as key regulators of glycolysis. When respiration was inhibited or oxygen was limited, a gal4tye7 C. albicans strain showed a severe growth defect when cultured on glucose, fructose or mannose as carbon sources. The gal4tye7 strain displayed attenuated virulence in both Galleria and mouse models as well, supporting the connection between pathogenicity and metabolism. Chromatin immunoprecipitation coupled with microarray analysis (ChIP-CHIP) and transcription profiling revealed that Tye7p bound the promoter sequences of the glycolytic genes and activated their expression during growth on either fermentable or non-fermentable carbon sources. Gal4p also bound the glycolytic promoter sequences and activated the genes although to a lesser extent than Tye7p. Intriguingly, binding and activation by Gal4p was carbon source-dependent and much stronger during growth on media containing fermentable sugars than on glycerol. Furthermore, Tye7p and Gal4p were responsible for the complete induction of the glycolytic genes under hypoxic growth conditions. Tye7p and Gal4p also regulated unique sets of carbohydrate metabolic genes; Tye7p bound and activated genes involved in trehalose, glycogen, and glycerol metabolism, while Gal4p regulated the pyruvate dehydrogenase complex. This suggests that Tye7p represents the key transcriptional regulator of carbohydrate metabolism in C. albicans and Gal4p provides a carbon source-dependent fine-tuning of gene expression while regulating the metabolic flux between respiration and fermentation pathways.
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C. albicans is a petite-negative and Crabtree-negative species that prefers respiration, although respiratory-deficient mutants remain viable as long as they retain the ability to maintain intact mtDNA.
“Candida albicans, on the other hand, is a petite-negative and Crabtree-negative species that prefers respiration (Askew et al. 2009), although respiratory-deficient mutants remain viable as long as they retain the ability to maintain intact mtDNA (Łabędzka-Dmoch et al. 2021, 2022, Wenda et al. 2024).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Askew et al. 2009
The Discussion states that C. albicans is Crabtree-negative and prefers respiration under aerobic conditions. Our copy does not establish that it is petite-negative; searches for petite-negative status and mitochondrial-DNA loss found no supporting passage. The respiratory-deficient-mutant clause is cited to other works, not Askew et al., so it is not assessed here. (LLM, conf=0.86)
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References 64 · Cited by 260
Research works printed but not linked: 2
- [53]Ausubel FM Brent R Kingston RE Moore DD Seidman JG 1992 Struhl K New York John Wiley and Sons
- [58]Nantel A Rigby T Hogues H Whiteway M 2006 Kavanaugh K Microarrays for studying pathology in Candida albicans Hoboken, NJ Wiley Press
- Authors
- Askew, C., Sellam, A., Epp, E., Hogues, H., Mullick, A., Nantel, A., & Whiteway, M.
- Affiliations
- Biotechnology Research Institute (CA)
- Corresponding author
- Whiteway, Malcolm
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-10-09
- Volume
- 5
- Issue
- 10
- Pages
- e1000612
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2749448
- OpenAlex
- W1986207589
- Cited by
- 260
- References
- 64
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 16 · 2023: 16 · 2022: 11 · 2021: 22 · 2020: 25 · 2019: 13 · 2018: 14 · 2017: 16 · 2016: 9 · 2015: 17 · 2014: 20 · 2013: 11 · 2012: 15
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- NPARC (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Canadian Institutes of Health Research (CTP79843, MOP42516)
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- Candida albicans, glycolysis, carbohydrate metabolism, transcriptional regulation, Gal4p, hypoxia, virulence, trehalose metabolism, glycogen metabolism, glycerol metabolism, pyruvate dehydrogenase complex, fungal pathogenesis
- MeSH terms
- Adenosine Triphosphate, Animals, Candida albicans, Candidiasis, Citric Acid Cycle, DNA-Binding Proteins, Fermentation, Glycolysis, Humans, Oxygen, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Virulence, Gene Expression Regulation, Fungal, Models, Animal, Saccharomyces cerevisiae Proteins, Carbohydrate Metabolism, Mice
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