Analysis of a fungus‐specific transcription factor family, the C andida albicans zinc cluster proteins, by artificial activation
Abstract
Summary: The zinc cluster proteins are a family of transcription factors that are unique to the fungal kingdom. In the pathogenic yeast C andida albicans, zinc cluster transcription factors control the expression of virulence‐associated traits and play key roles in the development of antifungal drug resistance. Gain‐of‐function mutations in several zinc cluster transcription factors, which result in constitutive overexpression of their target genes, are a frequent cause of azole resistance in clinical C. albicans isolates. We found that zinc cluster proteins can also be artificially activated by C‐terminal fusion with the heterologous Gal 4 activation domain. We used this strategy to create a comprehensive library of C. albicans strains expressing all 82 zinc cluster transcription factors of this fungus in a potentially hyperactive form. Screening of this library identified regulators of invasive filamentous growth and other phenotypes that are important during an infection. In addition, the approach uncovered several novel mediators of fluconazole resistance, including the multidrug resistance regulator Mrr 2, which controls the expression of the major C. albicans multidrug efflux pump CDR1. Artificial activation therefore is a highly useful method to study the role of zinc cluster transcription factors in C. albicans and other fungi of medical, agricultural and biotechnological importance.
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Addition of a 3 HA tag to the C-terminal domain of zinc cluster transcription factors is efficient for their artificial activation in C. albicans and C. auris.
“The addition of a 3 HA tag to the C-terminal domain of zinc cluster transcription factors was shown to be efficient for their artificial activation in C. albicans and C. auris, presumably by relieving an activation domain from repression by an inhibitory domain (32–35).”
From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [33]
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- Authors
- Schillig, R., & Morschhäuser, J.
- Affiliations
- University of Würzburg (DE)
- Corresponding author
- Morschhäuser, Joachim
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2013-07-25
- Volume
- 89
- Issue
- 5
- Pages
- 1003-1017
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1894827346
- Cited by
- 85
- References
- 8
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 1
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida albicans, zinc cluster transcription factors, azole resistance, fluconazole resistance, CDR1, multidrug efflux pumps, virulence gene expression, antifungal resistance, gain-of-function mutations
- MeSH terms
- Antifungal Agents, Candida albicans, Fungal Proteins, Genetics, Microbial, Molecular Biology, Mycology, Transcription Factors, Zinc, Transcriptional Activation, Fluconazole, Drug Resistance, Fungal
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