ArticlePloS one2015
New Mechanisms of Flucytosine Resistance in C. glabrata Unveiled by a Chemogenomics Analysis in S. cerevisiae.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Natural Product-Inspired Antifungal Drugs Introduced for Human Use from 1872 to August 2026.Antibiotics (Basel, Switzerland) · 2026Review
- Antifungal-induced DNA dynamics and chitin remodelling across Cryptococcus spp. and the novel broad-spectrum anti-cryptococcal candidate CPTH2.Scientific reports · 2026Article
- A novel lncRNA YIL163C enhances genomic stability and antifungal resistance via the DNA damage response inFrontiers in microbiology · 2025Article
- Proteasome inhibition as a therapeutic target for the fungal pathogenMicrobiology spectrum · 2023Article
- Cross-feeding affects the target of resistance evolution to an antifungal drug.PLoS genetics · 2023Article
- Vulvovaginal Candidiasis in Pregnancy-Between Sensitivity and Resistance to Antimycotics.Journal of xenobiotics · 2023Article
- Metabolic heterogeneity and cross-feeding within isogenic yeast populations captured by DILAC.Nature microbiology · 2023Article
- Factors Influencing the Nitrogen-Source Dependent Flucytosine Resistance in Cryptococcus Species.mBio · 2023Article
- The fungal expel of 5-fluorocytosine derived fluoropyrimidines mitigates its antifungal activity and generates a cytotoxic environment.PLoS pathogens · 2022Article
- Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications.The Journal of antimicrobial chemotherapy · 2022Review
- Fungal Infections as an Uprising Threat to Human Health: Chemosensitization of Fungal Pathogens With AFP FromFrontiers in cellular and infection microbiology · 2022Review
- Moderate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci.Nature communications · 2021Article
- Candidemia: Evolution of Drug Resistance and Novel Therapeutic Approaches.Infection and drug resistance · 2021Review
- Raman Imaging of PathogenicFrontiers in microbiology · 2021Article
- Review
- Antifungal Resistance inAntibiotics (Basel, Switzerland) · 2020Review
- Antifungal Drugs.Metabolites · 2020Review
- An Overview on Conventional and Non-Conventional Therapeutic Approaches for the Treatment of Candidiasis and Underlying Resistance Mechanisms in Clinical Strains.Journal of fungi (Basel, Switzerland) · 2020Review
- Article
- Microevolution of the pathogenic yeastsMicrobial cell (Graz, Austria) · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Flucytosine is currently used as an antifungal drug in combination therapy, but fungal pathogens are rapidly able to develop resistance against this drug, compromising its therapeutic action. The understanding of the underlying resistance mechanisms is crucial to deal with this problem. In this work, the S. cerevisiae deletion mutant collection was screened for increased resistance to flucytosine. Through this chemogenomics analysis, 183 genes were found to confer resistance to this antifungal agent. Consistent with its known effect in DNA, RNA and protein synthesis, the most significant Gene Ontology terms over-represented in the list of 5-flucytosine resistance determinants are related to DNA repair, RNA and protein metabolism. Additional functional classes include carbohydrate and nitrogen-particularly arginine-metabolism, lipid metabolism and cell wall remodeling. Based on the results obtained for S. cerevisiae as a model system, further studies were conducted in the pathogenic yeast Candida glabrata. Arginine supplementation was found to relieve the inhibitory effect exerted by 5-flucytosine in C. glabrata. Lyticase susceptibility was found to increase within the first 30min of 5-flucytosine exposure, suggesting this antifungal drug to act as a cell wall damaging agent. Upon exponential growth resumption in the presence of 5-flucytosine, the cell wall exhibited higher resistance to lyticase, suggesting that cell wall remodeling occurs in response to 5-flucytosine. Additionally, the aquaglyceroporin encoding genes CgFPS1 and CgFPS2, from C. glabrata, were identified as determinants of 5-flucytosine resistance. CgFPS1 and CgFPS2 were found to mediate 5-flucytosine resistance, by decreasing 5-flucytosine accumulation in C. glabrata cells.
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