ArticleCurrent genetics2019
Transcription factor CCG-8 plays a pivotal role in azole adaptive responses of Neurospora crassa by regulating intracellular azole accumulation.
Article in Current genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Regulation of ABC Transporters and Ergosterol Biosynthesis by the Transcription Factor FvADS-1 Controls Azole Resistance and Virulence inJournal of fungi (Basel, Switzerland) · 2026Article
- Article
- Suppressed Protein Translation Caused by MSP-8 Deficiency Determines Fungal Multidrug Resistance with Fitness Cost.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Global Analysis of microRNA-like RNAs Reveals Differential Regulation of Pathogenicity and Development inJournal of fungi (Basel, Switzerland) · 2024Article
- Coordinated Regulation of Membrane Homeostasis and Drug Accumulation by Novel Kinase STK-17 in Response to Antifungal Azole Treatment.Microbiology spectrum · 2022Article
- Experimental Evolution of Multidrug Resistance inJournal of fungi (Basel, Switzerland) · 2022Article
- Fungal Zn(II)Antimicrobial agents and chemotherapy · 2021Article
- Two dominant selectable markers for genetic manipulation in Neurospora crassa.Current genetics · 2020Article
- Characterization of the promoter, downstream target genes and recognition DNA sequence of Mhy1, a key filamentation-promoting transcription factor in the dimorphic yeast Yarrowia lipolytica.Current genetics · 2020Article
- Systematic prediction of FFAT motifs across eukaryote proteomes identifies nucleolar and eisosome proteins with the predicted capacity to form bridges to the endoplasmic reticulum.Contact (Thousand Oaks (Ventura County, Calif.)) · 2019Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Azoles are the most widely used antifungals for controlling fungal infections in clinic and agriculture. Fungi can adapt to azole stress by rapidly activating the transcription of a number of genes, and some of these genes can elevate resistance to azoles. We had reported the transcription factor CCG-8 as a new regulator in the adaptation to antifungal azole stress in Neurospora crassa and Fusarium verticillioides. In this study, we further investigate the mechanisms by which CCG-8 promotes fungal adaptation to azole stress using N. crassa as a model. While deletion of ccg-8 made N. crassa hypersensitive to azoles, ccg-8 overexpression strain was more resistant to azoles than wild type, which further confirmed the positive role of ccg-8 in the adaptation to antifungal azoles. Liquid chromatography-mass spectrometry analysis showed that deletion of ccg-8 resulted in decrease of ergosterol biosynthesis, and high accumulation of toxic sterol 14α-methyl-3,6-diol and ketoconazole (KTC) in the cells, whereas intracellular accumulation of ketoconazole was decreased in the ccg-8 overexpression strain as compared to wild type. For analyzing the effect of CCG-8 on azole export, we tested the contribution of predicted multidrug transporters to azole resistance and found that CDR4 is the major contributor for azole efflux in N. crassa. Interestingly, overexpression of cdr4 or erg11 in the ccg-8 deletion mutant restored its hypersensitive phenotype and overexpression of cdr4 can reduce the level of intracellular KTC. However, the double mutant of ccg-8 and cdr4 was more sensitive than each single mutant, suggesting that drug efflux pump CDR4 plays less contribution for intracellular azole accumulation in the ccg-8 deletion mutant, and CCG-8 may regulate drug uptake. Together, our results revealed that CCG-8 plays a pivotal role in azole adaptive responses of N. crassa by regulating the drug accumulation in the cells.
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