Azole heteroresistance in Cryptococcus neoformans: Emergence of resistant clones with chromosomal disomy in the mouse brain during fluconazole treatment
Open accessAbstract
We have previously reported that Cryptococcus neoformans strains are innately heteroresistant to fluconazole in vitro , producing minor, highly resistant subpopulations due to adaptive formation of disomic chromosomes. Using a mouse model, we assessed the emergence of heteroresistant clones in the brain during fluconazole treatment and found that the occurrence of heteroresistant clones in vivo with chromosomal disomy is strain dependent. Interestingly, emergence of heteroresistant clones in vivo was unrelated to the strain's MIC to fluconazole.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
High-level heteroresistant strains in brain-infected mice, if untreated, have a 20-day mortality rate that can reach 100%.
“As for high-level heteroresistant strains in brain-infected mice, if untreated their 20-day mortality rate can reach 100% [160].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [160]
Strains with chr1 disomy can be isolated from mouse brain during treatment with fluconazole.
“Strains with chr1 disomy can also be isolated from mouse brain during treatment with fluconazole [160].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [160]
The primary HR mechanism in C. glabrata distinguishes itself from models in C. albicans and C. neoformans, where aneuploidy is a common driver.
“Mechanistically, the primary HR mechanism in C. glabrata distinguishes itself from models in C. albicans and C. neoformans, where aneuploidy is a common driver [27, 42, 43].”
From Calcineurin‐Dependent Stress Adaptation Enables Caspofungin Heteroresistance Leading to Stable Resistance in <i>Candida Glabrata</i> (2026) · cites this paper as [43]
Heteroresistance primarily occurs through the formation of aneuploid cells, both in vitro and in vivo.
“Heteroresistance primarily occurs through the formation of aneuploid cells, both in vitro and in vivo17,22,24 (Fig. 1)”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [24]
The citation lists haven’t been fetched yet
References 12 · Cited by 112
- Authors
- Sionov, E., Chang, Y. C., & Kwon-Chung, K. J.
- Affiliations
- National Institutes of Health (US)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2013-10
- Volume
- 57
- Issue
- 10
- Pages
- 5127-5130
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3811407
- OpenAlex
- W2134087230
- Cited by
- 112
- References
- 12
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 9 · 2023: 4 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 9 · 2018: 7 · 2017: 15 · 2016: 5 · 2015: 7 · 2014: 9
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Cryptococcus neoformans, fluconazole, resistant clones, mouse brain infection, antifungal therapy, strain-dependent resistance, minimum inhibitory concentration
- MeSH terms
- Animals, Antifungal Agents, Azoles, Brain, Cryptococcosis, Cryptococcus neoformans, Female, Fungal Proteins, Mice, Inbred BALB C, Microbial Sensitivity Tests, Fluconazole, Chromosomes, Fungal, Gene Dosage, Drug Resistance, Fungal, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
