ArticleMolecular biology and evolution2023
Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans.
Article in Molecular biology and evolution, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 47 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
- 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
- Species-Specific Susceptibility of Planktonic and Biofilm Forming Candida Strains to Cyclodextrin-Encapsulated Essential Oils.Pharmaceutics · 2026Article
- Recurrent mutations in the stress regulator Cap1 reveal a trade-off between azole resistance and oxidative stress response in Candida albicans.PLoS biology · 2026Article
- Persistence and spread of fluconazole-resistantMicrobial genomics · 2026Article
- Experimental Evolution of PathogenicMicroorganisms · 2026Review
- Development of a predictive model using automated machine learning for Carbapenem-resistant Organisms (CRO) infections in hospitalized patients.Frontiers in microbiology · 2026Article
- Stress-driven emergence of heritable non-genetic drug resistance.Research square · 2025Article
- Does the use of topical azoles have an impact on antifungal resistance?The Journal of antimicrobial chemotherapy · 2025Article
- Aneuploidy, polyploidy, and loss of heterozygosity distinguish serial bloodstream isolates ofbioRxiv : the preprint server for biology · 2025Article
- Heterogeneity ofMicrobiology spectrum · 2025Article
- Tolerance and heteroresistance to echinocandins inmSphere · 2025Review
- Article
- Antifungal effects of Metformin against Candida albicans by autophagy regulation.Journal of microbiology (Seoul, Korea) · 2025Article
- 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
- Uncovering the connection between tunicamycin-induced respiratory deficiency and reduced fluconazole tolerance inFrontiers in microbiology · 2025Article
- Understanding adaptation to fluconazole: comparative insights into tolerance and resistance inFrontiers in cellular and infection microbiology · 2025Article
- Impact of inter-species hybridisation on antifungal drug response in the Saccharomyces genus.BMC genomics · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Invasive fungal infections are a leading global cause of human mortality. Only three major classes of antifungal drugs are widely used, and resistance to all three classes can arise rapidly. The most widely prescribed antifungal drug, fluconazole, disseminates rapidly and reaches a wide range of concentrations throughout the body. The impact of drug concentration on the spectrum and effect of mutations acquired during adaptation is not known for any fungal pathogen, and how the specific level of a given stress influences the distribution of beneficial mutations has been poorly explored in general. We evolved 144 lineages from three genetically distinct clinical isolates of Candida albicans to four concentrations of fluconazole (0, 1, 8, and 64 μg/ml) and performed comprehensive phenotypic and genomic comparisons of ancestral and evolved populations. Adaptation to different fluconazole concentrations resulted in distinct adaptive trajectories. In general, lineages evolved to drug concentrations close to their MIC50 (the level of drug that reduces growth by 50% in the ancestor) tended to rapidly evolve an increased MIC50 and acquired distinct segmental aneuploidies and copy number variations. By contrast, lineages evolved to drug concentrations above their ancestral MIC50 tended to acquire a different suite of mutational changes and increased in drug tolerance (the ability of a subpopulation of cells to grow slowly above their MIC50). This is the first evidence that different concentrations of drug can select for different genotypic and phenotypic outcomes in vitro and may explain observed in vivo drug response variation.
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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.