| Autor: |
Fatima Zohra Delma, Dong-Hoon Yang, Alfredo Cabrera-Orefice, Jordy Coolen, Abdullah M. S. Al-Hatmi, Sarah A. Ahmed, Willem J. G. Melchers, Yun C. Chang, Kyung J. Kwon-Chung, Sybren de Hoog, Paul E. Verweij, Jochem B. Buil |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
npj Antimicrobials and Resistance, Vol 2, Iss 1, Pp 1-8 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2731-8745 |
| DOI: |
10.1038/s44259-024-00041-8 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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