Cited by 32Fungal and yeast genetics researchAntifungal resistance and susceptibilityDrug Transport and Resistance Mechanisms

CDR4 is the major contributor to azole resistance among four Pdr5p-like ABC transporters in Neurospora crassa.

Zhang, Yu, Zhang, Zhenying, Zhang, Xinyu, Zhang, Hanxing, Sun, Xianyun, Hu, Chengcheng, Li, Shaojie·2012·Fungal Biology

Abstract

Pdr5p-like ABC transporters play a significant role in azole resistance in Saccharomyces cerevisiae and Candida spp. Most of filamentous fungal species have multiple Pdr5p homologues. In this study, phylogenic analysis identified that filamentous fungi have at least two phylogenically distant groups of Pdr5p homologues. One contains PMR1-like Pdr5p homologues while the other contains both AtrF-like and AtrB-like Pdr5p homologues. Neurospora crassa has a total of four genes encoding Pdr5p homologues including CDR4 (PMR1-like), ATRB (AtrB-like), and ATRF (AtrF-like) and ATRF-2 (AtrF-like). By analyzing the susceptibilities of their knockout mutants to azole drugs including ketoconazole, fluconazole, and itraconazole, we found that deletion of cdr4 increased the susceptibility to antifungal azoles. In contrast, neither single-gene nor triple-gene deletion of atrb, atrf, and atrf-2 could not alter the susceptibility to azoles. In addition, cdr4, but not other Pdr5p homologue-coding genes, responded transcriptionally to ketoconazole stress. Together with the previous findings in other fungal species, these results suggest that the PMR1-like but not the AtrF-like or AtrB-like Pdr5p homologues play a key role in antifungal azole resistance in filamentous fungi.

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Crossref · 10.1016/j.funbio.2012.05.002

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Authors
Zhang, Y., Zhang, Z., Zhang, X., Zhang, H., Sun, X., Hu, C., & Li, S.
Affiliations
Chinese Academy of Sciences (CN)
Corresponding author
Li, Shaojie
Venue
Fungal Biology
Publisher
Elsevier BV
Published
2012-07
Volume
116
Issue
7
Pages
848-854
ISSN
1878-6146 (ISSN-L)
OpenAlex
W2040555515
Cited by
32
References
29
Citations by year
2025: 4 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 4
FWCI
1.03
Type
journal article
Language
en
Open access
closed
Locations
  • Fungal Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • Chinese Academy of Sciences
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 › Oncology › Drug Transport and Resistance Mechanisms
Keywords
azole resistance, Neurospora crassa, ketoconazole, fluconazole, itraconazole, antifungal susceptibility, knockout mutants, filamentous fungi, phylogenetic analysis
MeSH terms
Antifungal Agents, Fungal Proteins, Ketoconazole, Microbial Sensitivity Tests, Neurospora crassa, Phylogeny, Fluconazole, Sequence Homology, Amino Acid, Itraconazole, ATP-Binding Cassette Transporters, Drug Resistance, Fungal, Gene Knockout Techniques

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