ArticleMolecular microbiology2018
Positive autoregulation and repression of transactivation are key regulatory features of the Candida glabrata Pdr1 transcription factor.
Article in Molecular microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Candida glabrata YPK2 is a multidrug susceptibility locus.Genetics · 2026Article
- Article
- FungAMR: a comprehensive database for investigating fungal mutations associated with antimicrobial resistance.Nature microbiology · 2025Article
- Hybrid adaptation is hampered by Haldane's sieve.Nature communications · 2024Article
- Overlapping coactivator function is required for transcriptional activation by the Candida glabrata Pdr1 transcription factor.Genetics · 2024Article
- Exploring the stress response mechanisms to 2-phenylethanol conferred by Pdr1p mutation in Saccharomyces cerevisiae.Biotechnology for biofuels and bioproducts · 2024Article
- The role of the Mediator complex in fungal pathogenesis and response to antifungal agents.Essays in biochemistry · 2023Review
- Redefining pleiotropic drug resistance in a pathogenic yeast: Pdr1 functions as a sensor of cellular stresses inmSphere · 2023Article
- Fungal Drug Response and Antimicrobial Resistance.Journal of fungi (Basel, Switzerland) · 2023Review
- Characterizing Candida glabrata Pdr1, a Hyperactive Transcription Factor Involved in Azole Resistance.Methods in molecular biology (Clifton, N.J.) · 2023Article
- yEvo: experimental evolution in high school classrooms selects for novel mutations that impact clotrimazole resistance in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2022Article
- Article
- Disclosing azole resistance mechanisms in resistant Candida glabrata strains encoding wild-type or gain-of-function CgPDR1 alleles through comparative genomics and transcriptomics.G3 (Bethesda, Md.) · 2022Article
- Azole-Resistant Alleles ofAntimicrobial agents and chemotherapy · 2022Article
- Copper Acts Synergistically With Fluconazole inFrontiers in microbiology · 2022Article
- The Candida glabrata Upc2A transcription factor is a global regulator of antifungal drug resistance pathways.PLoS genetics · 2021Article
- Functional information from clinically-derived drug resistant forms of the Candida glabrata Pdr1 transcription factor.PLoS genetics · 2020Article
- Article
- Multiple interfaces control activity of the Candida glabrata Pdr1 transcription factor mediating azole drug resistance.Current genetics · 2019Review
- Negative regulation of Candida glabrata Pdr1 by the deubiquitinase subunit Bre5 occurs in a ubiquitin independent manner.Molecular microbiology · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to azole drugs, the major clinical antifungal compounds, is most commonly due to gain-of-function (GOF) substitution mutations in a gene called PDR1 in the fungal pathogen Candida glabrata. PDR1 encodes a zinc cluster-containing transcription factor. GOF forms of Pdr1 drive high level expression of downstream target gene expression with accompanying azole resistance. PDR1 has two homologous genes in Saccharomyces cerevisiae, called ScPDR1 and ScPDR3. This study provides evidence that the PDR1 gene in C. glabrata represents a blend of the properties found in the two S. cerevisiae genes. We demonstrated that GOF Pdr1 derivatives are overproduced at the protein level and less stable than the wild-type protein. Overproduction of wild-type Pdr1 increased target gene expression but to a lesser extent than GOF derivatives. Site-directed mutagenesis of Pdr1 binding sites in the PDR1 promoter provided clear demonstration that autoregulation of PDR1 is required for its normal function. An internal deletion mutant of Pdr1 lacking its central regulatory domain behaved as a hyperactive transcription factor that was lethal unless conditionally expressed. A full understanding of the regulation of Pdr1 will provide a new avenue of interfering with azole resistance in C. glabrata.
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