Sterol C-22 desaturase ERG5 mediates the sensitivity to antifungal azoles in Neurospora crassa and Fusarium verticillioides.
Open accessAbstract
Antifungal azoles inhibit ergosterol biosynthesis by interfering with lanosterol 14α-demethylase. In this study, seven upregulated and four downregulated ergosterol biosynthesis genes in response to ketoconazole treatment were identified in Neurospora crassa. Azole sensitivity test of knockout mutants for six ketoconazole-upregulated genes in ergosterol biosynthesis revealed that deletion of only sterol C-22 desaturase ERG5 altered sensitivity to azoles: the erg5 mutant was hypersensitive to azoles but had no obvious defects in growth and development. The erg5 mutant accumulated higher levels of ergosta 5,7-dienol relative to the wild type but its levels of 14α-methylated sterols were similar to the wild type. ERG5 homologs are highly conserved in fungal kingdom. Deletion of Fusarium verticillioides erg5 also increased ketoconazole sensitivity, suggesting that the roles of ERG5 homologs in azole resistance are highly conserved among different fungal species, and inhibition of ERG5 could reduce the usage of azoles and thus provide a new target for drug design.
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The responsive C-22 sterol desaturase coding gene is important for basal resistance to azoles in N. crassa and Fusarium verticillioides.
“The responsive C-22 sterol desaturase coding gene was also demonstrated to be important for the basal resistance to azoles in N. crassa and Fusarium verticillioides (Sun et al., 2013).”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Sun et al., 2013
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References 38 · Cited by 37
- Authors
- Sun, X., Wang, W., Wang, K., Yu, X., Liu, J., Zhou, F., Xie, B., & Li, S.
- Affiliations
- Chinese Academy of Sciences (CN)
- Fujian Agriculture and Forestry University (CN)
- Yangzhou University (CN)
- Corresponding author
- Li, Shaojie
- Venue
- Frontiers in Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 4
- Pages
- 127-127
- ISSN
- 1664-302X (ISSN-L)
- PMC
- PMC3666115
- OpenAlex
- W2171996735
- Cited by
- 37
- References
- 38
- Citations by year
- 2026: 6 · 2024: 5 · 2023: 4 · 2022: 3 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Microbiology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31000551, 31170087)
- 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
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- ketoconazole, ergosterol biosynthesis, Neurospora crassa, Fusarium verticillioides, lanosterol 14α-demethylase, azole resistance, knockout mutants, antifungal drug targets
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