Articlenpj antimicrobials and resistance2024
Genetic mutations in Cryptococcus neoformans pyrimidine salvage pathway enzymes contribute to reduced susceptibility against 5-fluorocytosine.
Article in npj antimicrobials and resistance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- The shape of fitness functions and the distribution of mutational effect sizes jointly limit adaptation by regulatory mutations.Nature ecology & evolution · 2026Article
- Genomic Characterization ofVeterinary sciences · 2025Article
- New Ground in Antifungal Discovery and Therapy for Invasive Fungal Infections: Innovations, Challenges, and Future Directions.Journal of fungi (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cryptococcal meningitis is a high-mortality infection. Adding 5-fluorocytosine (5-FC) to its treatment improves outcomes, but resistance to 5-FC presents a significant challenge. We conducted whole-genome sequencing on seven C. neoformans isolates with varying 5-FC susceptibility, along with proteomic and in silico analyses. Our findings indicate that mutations in genes of the pyrimidine salvage pathway are responsible for 5-FC resistance. Specifically, we identified an E64G missense mutation in the FUR1 gene, a large deletion in the FCY1 gene, and a point mutation in FCY1 leading to a truncated protein. The proteomic data indicated that these mutations resulted in the absence or reduction of crucial enzymes in resistant isolates. Genetic transformations confirmed the association between these mutations and 5-FC resistance. Resistance to 5-FC can develop during treatment and is closely tied to mutations in key metabolic enzymes. Understanding in vivo resistance development is crucial for combating resistance and enhancing patient outcomes.
Identifiers
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Registered trials
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