Functional Analysis of cis - and trans -Acting Elements of the Candida albicans CDR2 Promoter with a Novel Promoter Reporter System
Open accessAbstract
Azole resistance in Candida albicans can be mediated by the upregulation of the ATP binding cassette transporter genes CDR1 and CDR2. Both genes are regulated by a cis-acting element called the drug-responsive element (DRE), with the consensus sequence 5'-CGGAWATCGGATATTTTTTT-3', and the transcription factor Tac1p. In order to analyze in detail the DRE sequence necessary for the regulation of CDR1 and CDR2 and properties of TAC1 alleles, a one-hybrid system was designed. This system is based on a P((CDR2))-HIS3 reporter system in which complementation of histidine auxotrophy can be monitored by activation of the reporter system by CDR2-inducing drugs such as estradiol. Our results show that most of the modifications within the DRE, but especially at the level of CGG triplets, strongly reduce CDR2 expression. The CDR2 DRE was replaced by putative DREs deduced from promoters of coregulated genes (CDR1, RTA3, and IFU5). Surprisingly, even if Tac1p was able to bind these putative DREs, as shown by chromatin immunoprecipitation, those from RTA3 and IFU5 did not functionally replace the CDR2 DRE. The one-hybrid system was also used for the identification of gain-of-function (GOF) mutations either in TAC1 alleles from clinical C. albicans isolates or inserted in TAC1 wild-type alleles by random mutagenesis. In all, 17 different GOF mutations were identified at 13 distinct positions. Five of them (G980E, N972D, A736V, T225A, and N977D) have already been described in clinical isolates, and four others (G980W, A736T, N972S, and N972I) occurred at already-described positions, thus suggesting that GOF mutations can occur in a limited number of positions in Tac1p. In conclusion, the one-hybrid system developed here is rapid and powerful and can be used for characterization of cis- and trans-acting elements in C. albicans.
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Upregulation of these pumps can be attributed to at least 17 different mutations in their transcriptional regulator TAC1.
“and the upregulation of these pumps can be attributed to at least 17 different mutations in their transcriptional regulator TAC1 [79,80].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [79]
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- Authors
- Coste, A. T., Crittin, J., Bauser, C., Rohde, B., & Sanglard, D.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Institute of Microbiology, University of Lausanne and University Hospital Center, CH-1011 Lausanne, Switzerland
- GATC Biotech (Germany) (DE)
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2009-08
- Volume
- 8
- Issue
- 8
- Pages
- 1250-1267
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC2725566
- OpenAlex
- W2137513397
- Cited by
- 79
- References
- 24
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 11 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Research Foundation
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- Candida albicans, azole resistance, ABC transporters, CDR1, gain-of-function mutations, cis-regulatory elements, trans-acting elements, transcriptional regulation
- MeSH terms
- Candida albicans, Estradiol, Fungal Proteins, Genetic Techniques, Histidine, Promoter Regions, Genetic, Protein Binding, Gene Expression Regulation, Fungal, Genes, Reporter, ATP-Binding Cassette Transporters, Response Elements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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