Genetic mutations in Cryptococcus neoformans pyrimidine salvage pathway enzymes contribute to reduced susceptibility against 5-fluorocytosine.

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 t

SUBMITTER: Delma FZ 

PROVIDER: S-EPMC11721657 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature