ArticlePLoS biology2014
A tetraploid intermediate precedes aneuploid formation in yeasts exposed to fluconazole.
Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 182 citations in OpenAlex.
- Beyond antifungal susceptibility: molecular mechanisms, detection, and clinical implications of fungal heteroresistance.Molecular biology reports · 2026Review
- Evolutionary adaptation proceeds through a small number of phenotypic modules.Molecular biology and evolution · 2026Article
- Growth under pressure: The pros and cons of polyploidy induced by stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Review
- Genetic and environmental control of parasexual reproduction in the pathogenicMicrobiology and molecular biology reviews : MMBR · 2025Review
- Stress-driven emergence of heritable non-genetic drug resistance.Research square · 2025Article
- Aneuploidy, polyploidy, and loss of heterozygosity distinguish serial bloodstream isolates ofbioRxiv : the preprint server for biology · 2025Article
- Expansion of the functional genomics GRACE library reveals genes relevant for temperature-dependent fitness in Candida albicans.PLoS biology · 2025Article
- Understanding the mechanisms of resistance to azole antifungals inJAC-antimicrobial resistance · 2025Review
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- Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans.Nature communications · 2025Article
- An agricultural triazole induces genomic instability and haploid cell formation in the human fungal pathogen Candida tropicalis.PLoS biology · 2025Article
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- Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance.Journal of fungi (Basel, Switzerland) · 2025Review
- The impact of phenotypic heterogeneity on fungal pathogenicity and drug resistance.FEMS microbiology reviews · 2025Review
- The role of gene copy number variation in antimicrobial resistance in human fungal pathogens.npj antimicrobials and resistance · 2025Review
- Recent Advances in Antimicrobial Resistance: Insights fromMicroorganisms · 2024Review
- Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans.Nature microbiology · 2024Article
- Adaptation of Candida albicans to specific host environments by gain-of-function mutations in transcription factors.PLoS pathogens · 2024Review
- Evolution and strain diversity advance exploration ofmSphere · 2024Review
- Whole-genome duplication in the Multicellularity Long Term Evolution Experiment.bioRxiv : the preprint server for biology · 2024Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Candida albicans, the most prevalent human fungal pathogen, is generally diploid. However, 50% of isolates that are resistant to fluconazole (FLC), the most widely used antifungal, are aneuploid and some aneuploidies can confer FLC resistance. To ask if FLC exposure causes or only selects for aneuploidy, we analyzed diploid strains during exposure to FLC using flow cytometry and epifluorescence microscopy. FLC exposure caused a consistent deviation from normal cell cycle regulation: nuclear and spindle cycles initiated prior to bud emergence, leading to "trimeras," three connected cells composed of a mother, daughter, and granddaughter bud. Initially binucleate, trimeras underwent coordinated nuclear division yielding four daughter nuclei, two of which underwent mitotic collapse to form a tetraploid cell with extra spindle components. In subsequent cell cycles, the abnormal number of spindles resulted in unequal DNA segregation and viable aneuploid progeny. The process of aneuploid formation in C. albicans is highly reminiscent of early stages in human tumorigenesis in that aneuploidy arises through a tetraploid intermediate and subsequent unequal DNA segregation driven by multiple spindles coupled with a subsequent selective advantage conferred by at least some aneuploidies during growth under stress. Finally, trimera formation was detected in response to other azole antifungals, in related Candida species, and in an in vivo model for Candida infection, suggesting that aneuploids arise due to azole treatment of several pathogenic yeasts and that this can occur during the infection process.
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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.