Whole Genome Analysis of Echinocandin Non‐Susceptible Candida Glabrata Clinical Isolates: a Multi‐Center Study in China
Open accessAbstract
Background: Candida glabrata is an important cause of invasive candidiasis. Echinocandins are the first-line treatment of invasive candidiasis caused by C. glabrata. The epidemiological echinocandin sensitivity requires long-term surveillance and the understanding about whole genome characteristics of echinocandin non-susceptible isolates was limited. Results: The present study investigated the echinocandin susceptibility of 1650 C. glabrata clinical isolates in China from August 2014 to July 2019. The in vitro activity of micafungin was significantly better than those of caspofungin and anidulafungin (P < 0.001), assessed by MIC 50/90 values. Whole genome sequencing was conducted on non-susceptible isolates and geography-matched susceptible isolates. Thirteen isolates (0.79%) were resistant to at least one echinocandin. Six isolates (0.36%) were solely intermediate to caspofungin. Common evolutionary analysis of echinocandin-resistant and echinocandin-intermediate isolates revealed genes related with reduced caspofungin sensitivity, including previously identified sphinganine hydroxylase encoding gene SUR2. Genome-wide association study identified SNPs at subtelometric regions that were associated with echinocandin non-susceptibility. In-host evolution of echinocandin resistance of serial isolates revealed an enrichment for non-synonymous mutations in adhesins genes and loss of subtelometric regions containing adhesin genes. Conclusions: The echinocandins are highly active against C. glabrata in China with a resistant rate of 0.79%. Echinocandin non-susceptible isolates carried common evolved genes which are related with reduced caspofungin sensitivity. In-host evolution of C. glabrata accompanied intensive changing of adhesins profile.
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An initially susceptible HR strain, cgl180, evolved to resistance during the infection course.
“In our previous research, an initially susceptible HR strain, cgl180, evolved to resistance during the infection course [32].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in <i>Candida Glabrata</i> (2026) · cites this paper as [32]
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- Authors
- Li, Y., Hou, X., Li, R., Liao, K., Ma, L., Wang, X., Ji, P., Kong, H., Xia, Y., Ding, H., Kang, W., Zhang, G., Li, J., Xiao, M., Li, Y., & Xu, Y.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking University (CN)
- Wuhan Union Hospital (CN)
- First Hospital of Jilin University (CN)
- First Affiliated Hospital of Xinjiang Medical University (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Lishui Central Hospital (CN)
- Venue
- BMC Microbiology
- Published
- 2023-11-16
- Volume
- 23
- Issue
- 1
- Pages
- 341-341
- ISSN
- 1471-2180 (ISSN-L)
- PMC
- PMC10652494
- OpenAlex
- W4388724933
- Cited by
- 7
- References
- 47
- Citations by year
- 2026: 3 · 2025: 3 · 2023: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-11-30)
- Open access
- gold
- doi.org
- Locations
- BMC Microbiology (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 (82002178, 32000024, 81971979)
- National Key Research and Development Program of China (2022YFC2303002)
- National High Level Hospital Clinical Research Funding (2022-PUMCH-C-052)
- 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 glabrata, echinocandin resistance, caspofungin, invasive candidiasis, SUR2, subtelomeric regions, adhesin genes, non-synonymous mutations, antifungal resistance, clinical isolates
- MeSH terms
- Caspofungin, Antifungal Agents, Candidiasis, China, Humans, Microbial Sensitivity Tests, Drug Resistance, Fungal, Candida glabrata, Echinocandins, Genome-Wide Association Study, Candidiasis, Invasive
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