Candida albicans Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure
Open accessAbstract
Candida albicans is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of FKS1 resistance mutations. We used six previously characterized mutants that decreased caspofungin susceptibility either by acquiring aneuploidy of chromosome 5 (Ch5) or by aneuploidy-independent mechanisms. When we exposed these caspofungin-adapted mutants to caspofungin again, we obtained 60 evolved mutants with further decreases in caspofungin susceptibility, as determined with CLSI method. We show that the initial adaptation to caspofungin is coupled with the adaptation to other ECNs, such as micafungin and anidulafungin, in mutants with no ploidy change, but not in aneuploid mutants, which become more susceptible to micafungin and anidulafungin. Furthermore, we find that the initial mechanism of caspofungin adaptation determines the pattern of further adaptation as parentals with no ploidy change further adapt to all ECNs by relatively small decreases in susceptibility, whereas aneuploid parentals adapt to all ECNs, primarily by large decrease in susceptibilities. Our data suggest that either distinct or common mechanisms can govern adaptation to different ECNs.
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C. albicans heteroresistance to echinocandins is also related to chr5, as chr5 aneuploidy after caspofungin exposure gave cross-resistance to caspofungin, micafungin and anidulafungin.
“It is also related to chr5, as chr5 aneuploidy after caspofungin exposure gave cross-resistance to caspofungin, micafungin and anidulafungin [133].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [133]
Section 3.2 reports that mutants evolved from Ch5-aneuploid parents under further caspofungin exposure showed increased MICs to caspofungin, micafungin, and anidulafungin. But Section 3.1 says the initial Ch5-aneuploid mutants were more susceptible to micafungin and anidulafungin. The claim omits the essential further-exposure step and calls the resulting tolerance cross-resistance. (LLM, conf=0.88)
Experimental — accuracy not yet measuredC. albicans chr5 aneuploidy caused by caspofungin exposure can result in cross-resistance to caspofungin, micafungin and anidulafungin.
“For example, C. albicans chr5 aneuploidy caused by caspofungin exposure can result in cross-resistance to caspofungin, micafungin and anidulafungin [133]”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [133]
The Conclusions report that C. albicans mutants with chromosome 5 aneuploidy predominantly acquired high tolerance to all three echinocandins after further caspofungin exposure. But Section 3.1 says the initially adapted aneuploid mutants were more susceptible to micafungin and anidulafungin. The claim omits the further-exposure condition and calls the observed tolerance cross-resistance, which the paper distinguishes from clinical resistance. (LLM, conf=0.88)
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- Authors
- Husain, F., Yadav, A., Sah, S. K., Hayes, J. J., & Rustchenko, E.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Rustchenko, Elena
- Venue
- Microorganisms
- Publisher
- MDPI AG
- Published
- 2022-12-21
- Volume
- 11
- Issue
- 1
- Pages
- 23
- ISSN
- 2076-2607 (ISSN-L)
- PMC
- PMC9866909
- OpenAlex
- W4313574148
- Cited by
- 10
- References
- 26
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 3
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Microorganisms (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (R01AI141884, R01GM052426)
- 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
- Candida albicans, caspofungin, echinocandin resistance, aneuploidy, chromosome 5, FKS1 mutations, micafungin, anidulafungin, antifungal resistance, drug tolerance, fungal adaptation, antifungal susceptibility
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