ArticleMicrobiology spectrum2021
Adaptation to Fluconazole via Aneuploidy Enables Cross-Adaptation to Amphotericin B and Flucytosine in Cryptococcus neoformans.
Article in Microbiology spectrum, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Beyond antifungal susceptibility: molecular mechanisms, detection, and clinical implications of fungal heteroresistance.Molecular biology reports · 2026Review
- Aneuploidy promotes transient stress adaptation and metabolic flexibility in the human fungal pathogen Aspergillus fumigatus.Current biology : CB · 2026Article
- Variable ectopic heterochromatin islands provide an alternative route to antifungal heteroresistance inbioRxiv : the preprint server for biology · 2026Article
- Emerging evidence for a multitude of mechanisms and factors that determine amphotericin B resistance in pathogenic fungi.Cell surface (Amsterdam, Netherlands) · 2026Review
- Article
- Whole-chromosome duplications drive antimicrobial resistance inbioRxiv : the preprint server for biology · 2025Article
- Investigation of voriconazole heteroresistance in clinical isolates ofMicrobiology spectrum · 2025Article
- Disruption of the ATP-dependent unfoldase ClpX reverses antifungal resistance in Cryptococcus neoformans.Nature communications · 2025Article
- Cryptococcus.Current biology : CB · 2025Review
- Calcineurin controls the cytokinesis machinery during thermal stress inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance.Journal of fungi (Basel, Switzerland) · 2025Review
- Induction of pan-azole resistance inFrontiers in cellular and infection microbiology · 2025Article
- Advancing cryptococcal treatment: The role of nanoparticles in mitigating antifungal resistance.Current research in microbial sciences · 2025Review
- The role of gene copy number variation in antimicrobial resistance in human fungal pathogens.npj antimicrobials and resistance · 2025Review
- Article
- Conserved signalling functions for Mps1, Mad1 and Mad2 in the Cryptococcus neoformans spindle checkpoint.PLoS genetics · 2024Article
- Beyond resistance: antifungal heteroresistance and antifungal tolerance in fungal pathogens.Current opinion in microbiology · 2024Review
- Aneuploidy underlies brefeldin A-induced antifungal drug resistance inFrontiers in cellular and infection microbiology · 2024Article
- Ketoconazole induces reversible antifungal drug tolerance mediated by trisomy of chromosome R inFrontiers in microbiology · 2024Article
- Unveiling genome plasticity as a mechanism of non-antifungal-induced antifungal resistance inFrontiers in microbiology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The high morbidity and mortality of cryptococcal meningitis is due to the limited range of therapeutic options: only three classes of antifungal drugs are available (polyenes [amphotericin B], azoles [fluconazole], and pyrimidine analogues [flucytosine]). Fluconazole is the most widely used antifungal drug in sub-Saharan Africa, where cryptococcal meningitis is a major cause of death in patients infected with HIV. In this study, we found that exposure to fluconazole, even for short times (48 h) at subinhibitory concentrations, drove rapid adaptation of Cryptococcus neoformans serotype A strain H99 via the acquisition of different aneuploid chromosomes. These aneuploidies conferred heteroresistance to fluconazole. Importantly, most of the adaptors were cross-tolerant to flucytosine. Some of the aneuploid adaptors were not heteroresistant to fluconazole but were tolerant to amphotericin B. Thus, exposure to one antifungal drug class can promote adaptation to two antifungal drug classes, highlighting the plasticity of the C. neoformans genome and raising concerns about the rapid reduction in the range of treatment options for cryptococcal infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.