Beyond resistance: antifungal heteroresistance and antifungal tolerance in fungal pathogens
Open accessAbstract
Fungal infections are increasing globally, causing alarmingly high mortality and economic burden. In addition to antifungal resistance, other more subtle drug responses appear to increase the likelihood of treatment failures. These responses include heteroresistance and tolerance, terms that are more well-defined for antibacterial drugs, but are also evident in pathogenic fungi. Here, we compare these antifungal responses with similarly named antibacterial responses, and we review recent advances in how we understand the routes by which antifungal heteroresistance and tolerance emerge.
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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 [150]
The Antifungal drug resistance section reports aneuploidy-associated heteroresistance in C. neoformans, and the Conclusions call aneuploidy a clear route to heteroresistance. The review also notes heteroresistant isolates without detectable aneuploidy; it does not establish that aneuploidy is a common heritable mechanism or identify an aneuploidy-driven form as the most widely studied. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn multiple murine infection models, heteroresistant strains lead to increased fungal burden and reduced treatment efficacy.
“In multiple murine infection models, Heteroresistant strains can lead to increased fungal burden and reduced treatment efficacy [28,29].”
From Antifungal persistence: Clinical relevance and mechanisms (2025) · cites this paper as [29]
The review’s ‘Antifungal drug resistance’ section reports that fluconazole heteroresistance was associated with greater persistence of C. glabrata infection in one mouse model, and it links heteroresistance to breakthrough infections and possible treatment failure. It does not report increased fungal burden and reduced treatment efficacy across multiple murine infection models; the claim overstates the model-specific evidence. (LLM, conf=0.85)
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Research works printed but not linked: 1
- [6]Zhai B Liao C Jaggavarapu S Rolling T Bergin SA Gjonbalaj M Miranda E Babady NE Butler G Taur Y Echinocandin heteroresistance causes prophylaxis failure and facilitates breakthrough Candida parapsilosis infection medRxiv 2022 2022.2005.2029.22275734 ●● This work demonstrates prophylaxis failure of micafungin is due to heteroresistance 10.1038/s41591-024-03183-4 39095599 PMC11840754 · DOI · Paper page
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- Authors
- Yang, F., & Berman, J.
- Affiliations
- Tongji University (CN)
- Tel Aviv University (IL)
- Corresponding author
- Berman, Judith
- Venue
- Current Opinion in Microbiology
- Publisher
- Elsevier BV
- Published
- 2024-04
- Volume
- 78
- Pages
- 102439
- ISSN
- 1369-5274 (ISSN-L)
- PMC
- PMC7616270
- OpenAlex
- W4392119611
- Cited by
- 42
- References
- 41
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 9
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Current Opinion in Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-sa)
- PubMed Central (acceptedVersion)
- Funders
- Horizon 2020 Framework Programme (951475)
- Israel Science Foundation
- European Research Council
- Horizon 2020
- Natural Science Foundation of Shanghai Municipality (23ZR1449500)
- 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
- antifungal tolerance, antifungal resistance, fungal pathogens, fungal infection, drug response, treatment failure
- MeSH terms
- Anti-Bacterial Agents, Antifungal Agents, Humans, Drug Resistance, Fungal
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