A Small Molecule Inhibitor of Erg251 Makes Fluconazole Fungicidal by Inhibiting the Synthesis of the 14α-Methylsterols
Open accessAbstract
Fluconazole (FLC) tolerance increases the frequency of acquired FLC resistance, and a high FLC tolerance level is associated with persistent candidemia. Multiple functional proteins, such as calcineurin, heat shock protein 90 (Hsp90), and ADP ribosylation factor, are essential for the survival of C. albicans exposed to FLC, but how these factors increase the fungicidal activity of FLC remains to be determined.
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In the erg11∆/erg11∆ null mutant, the MIC value of PIT was lowered from 3.125 μg/mL in the control strain to 0.1953 μg/mL.
“To test this, we utilized an erg11∆/erg11∆ null mutant [42] and observed its MIC value of PIT lowered from 3.125 μg/mL in the control strain to 0.1953 μg/mL (Figure 5C), indicating that PIT has the potential to augment the antifungal efficacy of azoles.”
From Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species (2024) · cites this paper as [42]
The MIC of FLC is significantly decreased in C. albicans upc2∆/upc2∆ mutant.
“A previous study demonstrated that the minimum inhibitory concentration (MIC) of FLC was significantly decreased in C. albicans mutant with deletions in the UPC2 gene (upc2∆/upc2∆) [12,19].”
From Disruption of the UPC2 Gene Enhances Fluconazole Antifungal Activity by Inhibiting HAC1 mRNA Splicing in Candida albicans (2026) · cites this paper as [12]
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References 68 · Cited by 30
- Authors
- Lu, H., Li, W., Whiteway, M., Wang, H., Zhu, S., Ji, Z., Feng, Y., Yan, L., Fang, T., Li, L., Ni, T., Zhang, X., Lv, Q., Ding, Z., Qiu, L., Zhang, D., & Jiang, Y.
- Affiliations
- Tongji University (CN)
- Concordia University (CA)
- China Pharmaceutical University (CN)
- Second Military Medical University (CN)
- Corresponding author
- Zhang, Dazhi
- Jiang, Yuanying
- ORCID
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2023-02-28
- Volume
- 14
- Issue
- 1
- Pages
- e0263922-e0263922
- ISSN
- 2150-7511 (ISSN-L)
- PMC
- PMC9973333
- OpenAlex
- W4310946316
- Cited by
- 30
- References
- 68
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 14 · 2023: 5
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Innovation Program of Shanghai Municipal Education Commission (202101070007-E00094)
- MOST | National Key Research and Development Program of China (2021YFC2300404)
- National Natural Science Foundation of China (81830106, 82020108032)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- fluconazole, Candida albicans, ergosterol, fluconazole resistance, small molecule inhibitors, antifungal synergy, candidemia
- MeSH terms
- Antifungal Agents, Candida albicans, Fungicides, Industrial, Microbial Sensitivity Tests, Fluconazole, Drug Resistance, Fungal
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