ArticleNature communications2021
Moderate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 45 citations in OpenAlex.
- Natural Product-Inspired Antifungal Drugs Introduced for Human Use from 1872 to August 2026.Antibiotics (Basel, Switzerland) · 2026Review
- Current and emerging therapies for fungal biofilms and systemic infections.Critical reviews in microbiology · 2026Review
- Encapsulation of Flucytosine into nanoliposomes for enhanced antifungal activity against Candida glabrata and Candida albicans.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025Article
- In vitro and in vivo efficacy of the antimycobacterial molecule SQ109 against the human pathogenic fungus, Cryptococcus neoformans.PLoS neglected tropical diseases · 2025Article
- Next-Generation Sequencing for Bloodstream Infections: Shaping the Future of Rapid Diagnostics and Precision Medicine.Diagnostics (Basel, Switzerland) · 2025Review
- Role ofMicroorganisms · 2025Article
- 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
- Aneuploidy enables adaptation to brefeldin A inFrontiers in cellular and infection microbiology · 2025Article
- Multifocal Intracranial Cryptococcoma with Treatment Resistance, Recurrence, and Mortality: A Case Report and Literature Review.NMC case report journal · 2025Article
- New antifungal strategies and drug development against WHO critical priority fungal pathogens.Frontiers in cellular and infection microbiology · 2025Review
- Genomics insights of candidiasis: mechanisms of pathogenicity and drug resistance.Frontiers in microbiology · 2025Review
- Induction of pan-azole resistance inFrontiers in cellular and infection microbiology · 2025Article
- Multi-Locus Sequence Typing-Based Genetic Analysis, Antifungal Resistance, and Clinical Prognosis of Cryptococcus neoformans Infections in HIV-Infected Patients in Northern China.The American journal of tropical medicine and hygiene · 2024Article
- Distinct evolutionary trajectories following loss of RNA interference inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Distinct evolutionary trajectories following loss of RNA interference inbioRxiv : the preprint server for biology · 2024Article
- Genetic mutations in Cryptococcus neoformans pyrimidine salvage pathway enzymes contribute to reduced susceptibility against 5-fluorocytosine.npj antimicrobials and resistance · 2024Article
- ResFungi: A Novel Protein Database of Antifungal Drug Resistance Genes Using a Hidden Markov Model Profile.ACS omega · 2024Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The antifungal agent 5-fluorocytosine (5-FC) is used for the treatment of several mycoses, but is unsuitable for monotherapy due to the rapid development of resistance. Here, we show that cryptococci develop resistance to 5-FC at a high frequency when exposed to concentrations several fold above the minimal inhibitory concentration. The genomes of resistant clones contain alterations in genes relevant as well as irrelevant for 5-FC resistance, suggesting that 5-FC may be mutagenic at moderate concentrations. Mutations in FCY2 (encoding a known permease for 5-FC uptake), FCY1, FUR1, UXS1 (encoding an enzyme that converts UDP-glucuronic acid to UDP-xylose) and URA6 contribute to 5-FC resistance. The uxs1 mutants accumulate UDP-glucuronic acid, which appears to down-regulate expression of permease FCY2 and reduce cellular uptake of the drug. Additional mutations in genes known to be required for UDP-glucuronic acid synthesis (UGD1) or a transcriptional factor NRG1 suppress UDP-glucuronic acid accumulation and 5-FC resistance in the uxs1 mutants.
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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.