ArticlePLoS pathogens2017
A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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102 citing papers in PubMed, 146 citations in OpenAlex.
- Functional characterization of SHC-like triterpene cyclase genes in azole response and virulence-related traits ofVirulence · 2026Article
- The MoSR-MoDde1 Regulatory Axis: A Novel Determinant of DMI Sensitivity and a Target for Sustainable Rice Blast Control.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Comparative analysis of selective fungal culture media and incubation conditions forMicrobiology spectrum · 2026Article
- Antifungal resistance: from classical mechanisms to the expanding role of acetyltransferases.Journal of biomedical science · 2026Review
- Lipid-Based Drug Delivery Systems as Emerging Tools to Overcome Antifungal Resistance.International journal of molecular sciences · 2026Review
- Genotype-Phenotype Relationships in Azole-ResistantJournal of fungi (Basel, Switzerland) · 2026Review
- EneA of Aspergillus fumigatus is a regulator of secondary metabolism and enhances nscA expression in presence of polyenes and Streptomyces.Scientific reports · 2026Article
- Regulation of ABC Transporters and Ergosterol Biosynthesis by the Transcription Factor FvADS-1 Controls Azole Resistance and Virulence inJournal of fungi (Basel, Switzerland) · 2026Article
- Regulated proteolysis of green fluorescent protein fusion proteins in Aspergillus fumigatus.G3 (Bethesda, Md.) · 2026Article
- The molecular basis of intrinsic resistance to azoles inAntimicrobial agents and chemotherapy · 2026Article
- Chromatin Immunoprecipitation in Aspergillus fumigatus.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Electrophoretic Mobility Shift Assay in Aspergillus fumigatus.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Genomic variant-driven prediction of azole resistance inFrontiers in microbiology · 2026Article
- Multidrug efflux pumps and innate azole resistance of Mucor lusitanicus.The Journal of antimicrobial chemotherapy · 2025Article
- Azole-ResistantJournal of fungi (Basel, Switzerland) · 2025Review
- Article
- RttA, a ZnMicrobiology spectrum · 2025Article
- Pathogenic Fungal Sensing and Responses to Stressful Host Environments.Annual review of microbiology · 2025Review
- Agricultural SDHIs Induce Azole Resistance in Aspergillus fumigatus via Mitochondrial Sdh1 Suppression.Mycopathologia · 2025Article
- Aspergillosis: A comprehensive review of pathogenesis, drug resistance, and emerging therapeutics.Journal of food and drug analysis · 2025Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To elucidate mechanisms underlying azole resistance, we identified a novel transcription factor that is required for normal azole resistance in Aspergillus fungi including A. fumigatus, Aspergillus oryzae, and Aspergillus nidulans. This fungal-specific Zn2-Cys6 type transcription factor AtrR was found to regulate expression of the genes related to ergosterol biosynthesis, including cyp51A that encodes a target protein of azoles. The atrR deletion mutant showed impaired growth under hypoxic conditions and attenuation of virulence in murine infection model for aspergillosis. These results were similar to the phenotypes for a mutant strain lacking SrbA that is also a direct regulator for the cyp51A gene. Notably, AtrR was responsible for the expression of cdr1B that encodes an ABC transporter related to azole resistance, whereas SrbA was not involved in the regulation. Chromatin immunoprecipitation assays indicated that AtrR directly bound both the cyp51A and cdr1B promoters. In the clinically isolated itraconazole resistant strain that harbors a mutant Cyp51A (G54E), deletion of the atrR gene resulted in a hypersensitivity to the azole drugs. Together, our results revealed that AtrR plays a pivotal role in a novel azole resistance mechanism by co-regulating the drug target (Cyp51A) and putative drug efflux pump (Cdr1B).
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