Tandem gene duplications contributed to high-level azole resistance in a rapidly expanding Candida tropicalis population
Open accessAbstract
Invasive diseases caused by the globally distributed commensal yeast Candida tropicalis are associated with mortality rates of greater than 50%. Notable increases of azole resistance have been observed in this species, particularly within Asia-Pacific regions. Here, we carried out a genetic population study on 1571 global C. tropicalis isolates using multilocus sequence typing (MLST). In addition, whole-genome sequencing (WGS) analysis was conducted on 629 of these strains, comprising 448 clinical invasive strains obtained in this study and 181 genomes sourced from public databases. We found that MLST clade 4 is the predominant azole-resistant clone. WGS analyses demonstrated that dramatically increasing rates of azole resistance are associated with a rapid expansion of cluster AZR, a sublineage of clade 4. Cluster AZR isolates exhibited a distinct high-level azole resistance, which was induced by tandem duplications of the ERG11 A395T gene allele. Ty3/gypsy -like retrotransposons were found to be highly enriched in this population. The alarming expansion of C. tropicalis cluster AZR population underscores the urgent need for strategies against growing threats of antifungal resistance.
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Aneuploidy is a common heritable mechanism responsible for the most widely studied form of antifungal heteroresistance.
“Aneuploidy is a common heritable mechanism responsible for the most widely studied form of antifungal heteroresistance [148,149,150].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [149]
The Results report that chromosome 5 aneuploidy was associated with fluconazole resistance in the studied C. tropicalis isolates. But they found aneuploidy in only 2.1% of strains, and the Discussion says chromosome-level aneuploidy-induced azole resistance remained rare in this species. The paper does not establish that aneuploidy is a common heritable mechanism of antifungal heteroresistance or characterize it as the most widely studied form. (LLM, conf=0.82)
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References 68 · Cited by 55
Research works printed but not linked: 2
- [69]CLSI. M60: Performance Standards for Antifungal Susceptibility Testing of Yeasts, 2nd Edition (CLSI, 2020).
- [70]CLSI. M59: Epidemiological Cutoff Values for Antifungal Susceptibility Testing, 3rd Edition (CLSI, 2020).
- Authors
- Fan, X., Dai, R.-C., Zhang, S., Geng, Y.-Y., Kang, M., Guo, D.-W., Mei, Y.-N., Pan, Y.-H., Sun, Z.-Y., Xu, Y.-C., Gong, J., & Xiao, M.
- Affiliations
- Capital Medical University (CN)
- Chinese Center For Disease Control and Prevention (CN)
- Sichuan University (CN)
- Union Hospital (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Gong, Jie
- Xiao, Meng
- Venue
- Nature Communications
- Published
- 2023-12-15
- Volume
- 14
- Issue
- 1
- Pages
- 8369-8369
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10724272
- OpenAlex
- W4389781763
- Cited by
- 55
- References
- 68
- Citations by year
- 2026: 24 · 2025: 19 · 2024: 12
- FWCI
- 11.32
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-01-18)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- National Natural Science Foundation of China (81802042)
- Peking Union Medical College Hospital
- Peking Union Medical College
- National Key Research and Development Program of China (2022YFC2303002)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
- Keywords
- Candida tropicalis, azole resistance, tandem gene duplication, ERG11, Ty3/gypsy retrotransposons, antifungal resistance, invasive candidiasis, population genomics, clinical isolates, drug resistance evolution
- MeSH terms
- Antifungal Agents, Azoles, Microbial Sensitivity Tests, Gene Duplication, Drug Resistance, Fungal, Candida tropicalis, Multilocus Sequence Typing
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