ArticleNature communications2020
5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus.
Article in Nature communications, 2020. 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, 111 citations in OpenAlex.
- De novo or Salvage? Nucleotide Availability as a Driver of Bacterial Adaptation and Virulence.MicrobiologyOpen · 2026Review
- Antifungal-induced DNA dynamics and chitin remodelling across Cryptococcus spp. and the novel broad-spectrum anti-cryptococcal candidate CPTH2.Scientific reports · 2026Article
- Current and emerging therapies for fungal biofilms and systemic infections.Critical reviews in microbiology · 2026Review
- Butyrolactol A enhances caspofungin efficacy via flippase inhibition in drug-resistant fungi.Cell · 2026Article
- Advances in cryptococcal infections-associated immunopathology and potential therapeutic strategies.Frontiers in pharmacology · 2026Review
- Butyrolactol A potentiates caspofungin efficacy against resistant fungi via phospholipid flippase inhibition.bioRxiv : the preprint server for biology · 2025Article
- Article
- The emerging fungal pathogen Cryptococcus gattii: Epidemiology, pathogenesis, immunomodulatory attributes, and drug susceptibility.PLoS neglected tropical diseases · 2025Review
- Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans.PLoS biology · 2025Article
- RapidmSphere · 2025Article
- Elevated UDP-glucuronic acid levels mend drug resistance and stress responses via a protease and a transporter 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
- The genome of the polyextremophilic yeast, Naganishia friedmannii, reveals adaptations involved in stress response pathways, carbohydrate metabolism expansion, and a limited DNA repair repertoire.FEMS yeast research · 2025Article
- New antifungal strategies and drug development against WHO critical priority fungal pathogens.Frontiers in cellular and infection microbiology · 2025Review
- A novel lncRNA YIL163C enhances genomic stability and antifungal resistance via the DNA damage response inFrontiers in microbiology · 2025Article
- Genomics insights of candidiasis: mechanisms of pathogenicity and drug resistance.Frontiers in microbiology · 2025Review
- Predicting patient outcomes with gene-expression biomarkers from colorectal cancer organoids and cell lines.Frontiers in molecular biosciences · 2025Article
- Advancing cryptococcal treatment: The role of nanoparticles in mitigating antifungal resistance.Current research in microbial sciences · 2025Review
- Transposon load and RNAi loss synergize to drive intraspecies diversity inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Elevated mutation rates in multi-azole resistant Aspergillus fumigatus drive rapid evolution of antifungal resistance.Nature communications · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Patients infected with the fungal pathogen Cryptococcus are most effectively treated with a combination of 5-fluorocytosine (5FC) and amphotericin B. 5FC acts as a prodrug, which is converted into toxic 5-fluorouracil (5FU) upon uptake into fungal cells. However, the pathogen frequently develops resistance through unclear mechanisms. Here we show that resistance to 5FC in Cryptococcus deuterogattii is acquired more frequently in isolates with defects in DNA mismatch repair that confer an elevated mutation rate. We use whole genome sequencing of 16 independent isolates to identify mutations associated with 5FC resistance in vitro. We find mutations in known resistance genes (FUR1 and FCY2) and in a gene UXS1, previously shown to encode an enzyme that converts UDP-glucuronic acid to UDP-xylose for capsule biosynthesis, but not known to play a role in 5FC metabolism. Mutations in UXS1 lead to accumulation of UDP-glucuronic acid and alterations in nucleotide metabolism, which appear to suppress toxicity of both 5FC and its toxic derivative 5FU.
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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.