ArticleMolecular biology and evolution2019
Aneuploidy Enables Cross-Adaptation to Unrelated Drugs.
Article in Molecular biology and evolution, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 106 citations in OpenAlex.
- A multiplex droplet digital PCR assay for chromosome copy-number determination in Candida albicans.G3 (Bethesda, Md.) · 2026Article
- CRISPR-activation reveals key resistance genes and vulnerabilities of copy number variants inbioRxiv : the preprint server for biology · 2026Article
- Antifungal resistance: from classical mechanisms to the expanding role of acetyltransferases.Journal of biomedical science · 2026Review
- Multi-drug tolerance in Leishmania persister-like cells.Communications biology · 2026Article
- Lipid-Based Drug Delivery Systems as Emerging Tools to Overcome Antifungal Resistance.International journal of molecular sciences · 2026Review
- Review
- Blood Cultures Contain Populations of Genetically Diverse Candida albicans Strains that May Differ in Echinocandin Tolerance and Fitness.The Journal of infectious diseases · 2026Article
- Aneuploidy, polyploidy, and loss of heterozygosity distinguish serial bloodstream isolates ofbioRxiv : the preprint server for biology · 2025Article
- Transcriptomic and Cytogenetic Analysis of Oxaliplatin-Resistant Colorectal Adenocarcinoma HCT116 Cells to Identify Markers Associated with Platinum Resistance.International journal of molecular sciences · 2025Article
- Genome restructuring and lineage diversification of Cryptococcus neoformans during chronic infection of human hosts.Cell reports · 2025Article
- Patterns and mechanisms of fungal genome plasticity.Current biology : CB · 2025Review
- Aneuploidy confers a unique transcriptional and phenotypic profile to Candida albicans.Nature communications · 2025Article
- Induction of Antifungal Tolerance Reveals Genetic and Phenotypic Changes inJournal of fungi (Basel, Switzerland) · 2025Article
- Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance.Journal of fungi (Basel, Switzerland) · 2025Review
- Aneuploidy enables adaptation to brefeldin A inFrontiers in cellular and infection microbiology · 2025Article
- Caspofungin paradoxical growth inFrontiers in cellular and infection microbiology · 2025Article
- The role of gene copy number variation in antimicrobial resistance in human fungal pathogens.npj antimicrobials and resistance · 2025Review
- Resistance Mechanisms of Plant Pathogenic Fungi to Fungicide, Environmental Impacts of Fungicides, and Sustainable Solutions.Plants (Basel, Switzerland) · 2024Review
- Evolution and strain diversity advance exploration ofmSphere · 2024Review
- Chromosome-Level Assembly Reveals a Fifteen-Chromosome Aneuploid Genome and Environmental Adaptation Strategy of Chinese Traditional Medical FungusInternational journal of molecular sciences · 2024Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Aneuploidy is common both in tumor cells responding to chemotherapeutic agents and in fungal cells adapting to antifungal drugs. Because aneuploidy simultaneously affects many genes, it has the potential to confer multiple phenotypes to the same cells. Here, we analyzed the mechanisms by which Candida albicans, the most prevalent human fungal pathogen, acquires the ability to survive both chemotherapeutic agents and antifungal drugs. Strikingly, adaptation to both types of drugs was accompanied by the acquisition of specific whole-chromosome aneuploidies, with some aneuploid karyotypes recovered independently and repeatedly from very different drug conditions. Specifically, strains selected for survival in hydroxyurea, an anticancer drug, acquired cross-adaptation to caspofungin, a first-line antifungal drug, and both acquired traits were attributable to trisomy of the same chromosome: loss of trisomy was accompanied by loss of adaptation to both drugs. Mechanistically, aneuploidy simultaneously altered the copy number of most genes on chromosome 2, yet survival in hydroxyurea or caspofungin required different genes and stress response pathways. Similarly, chromosome 5 monosomy conferred increased tolerance to both fluconazole and to caspofungin, antifungals with different mechanisms of action. Thus, the potential for cross-adaptation is not a feature of aneuploidy per se; rather, it is dependent on specific genes harbored on given aneuploid chromosomes. Furthermore, pre-exposure to hydroxyurea increased the frequency of appearance of caspofungin survivors, and hydroxyurea-adapted C. albicans cells were refractory to antifungal drug treatment in a mouse model of systemic candidiasis. This highlights the potential clinical consequences for the management of cancer chemotherapy patients at risk of fungal infections.
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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.