ArticleNature ecology & evolution2022
Asymmetrical dose responses shape the evolutionary trade-off between antifungal resistance and nutrient use.
Article in Nature ecology & evolution, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Mutational landscape and molecular bases of echinocandin resistance in Saccharomyces cerevisiae.Genetics · 2026Article
- Predicting antifolate resistance in the unculturable fungal pathogen Pneumocystis jirovecii.PLoS genetics · 2026Article
- Uncovering actionable trade-offs of antifungal resistance in a yeast pathogen.Molecular systems biology · 2026Article
- Phenotypic dominance emerges from activity fitness functions and molecular interactions.Genetics · 2026Article
- A cost-effective and scalable barcoded library construction method for deep mutational scanning studies.PLoS biology · 2026Article
- Article
- FungAMR: a comprehensive database for investigating fungal mutations associated with antimicrobial resistance.Nature microbiology · 2025Article
- Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network.Nature communications · 2025Article
- New antifungal strategies and drug development against WHO critical priority fungal pathogens.Frontiers in cellular and infection microbiology · 2025Review
- Unlocking the potential of experimental evolution to study drug resistance in pathogenic fungi.npj antimicrobials and resistance · 2024Review
- Acquired amphotericin B resistance leads to fitness trade-offs that can be mitigated by compensatory evolution in Candida auris.Nature microbiology · 2024Article
- Hybrid adaptation is hampered by Haldane's sieve.Nature communications · 2024Article
- Most azole resistance mutations in the Candida albicans drug target confer cross-resistance without intrinsic fitness cost.Nature microbiology · 2024Article
- Collateral sensitivity counteracts the evolution of antifungal drug resistance in Candida auris.Nature microbiology · 2024Article
- New approaches to tackle a rising problem: Large-scale methods to study antifungal resistance.PLoS pathogens · 2024Review
- Article
- Shaping of microbial phenotypes by trade-offs.Nature communications · 2024Review
- Article
- Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Antimicrobial resistance is an emerging threat for public health. The success of resistance mutations depends on the trade-off between the benefits and costs they incur. This trade-off is largely unknown and uncharacterized for antifungals. Here, we systematically measure the effect of all amino acid substitutions in the yeast cytosine deaminase Fcy1, the target of the antifungal 5-fluorocytosine (5-FC, flucytosine). We identify over 900 missense mutations granting resistance to 5-FC, a large fraction of which appear to act through destabilization of the protein. The relationship between 5-FC resistance and growth sustained by cytosine deamination is characterized by a sharp trade-off, such that small gains in resistance universally lead to large losses in canonical enzyme function. We show that this steep relationship can be explained by differences in the dose-response functions of 5-FC and cytosine. Finally, we observe the same trade-off shape for the orthologue of FCY1 in Cryptoccocus neoformans, a human pathogen. Our results provide a powerful resource and platform for interpreting drug target variants in fungal pathogens as well as unprecedented insights into resistance-function trade-offs.
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