{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Billmyre RB"],"funding":["U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","NIAID NIH HHS"],"pagination":["127"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6949227"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_abstract":["Patients infected with the fungal pathogen Cryptococcus are most effectively treated with a combination of 5-fluorocytosine (5FC) and amphotericin B. 5FC acts as a prodrug, which is converted into toxic 5-fluorouracil (5FU) upon uptake into fungal cells. However, the pathogen frequently develops resistance through unclear mechanisms. Here we show that resistance to 5FC in Cryptococcus deuterogattii is acquired more frequently in isolates with defects in DNA mismatch repair that confer an elevated mutation rate. We use whole genome sequencing of 16 independent isolates to identify mutations associated with 5FC resistance in vitro. We find mutations in known resistance genes (FUR1 and FCY2) and in a gene UXS1, previously shown to encode an enzyme that converts UDP-glucuronic acid to UDP-xylo"],"journal":["Nature communications"],"pubmed_title":["5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus."],"pmcid":["PMC6949227"],"funding_grant_id":["R37 AI039115","AI112595-04","AI39115-21","AI104533-05","AI120339","AI109623","R21 AI109623","AI50113-15","R01 AI135012","R01 AI050113"],"pubmed_authors":["Li LX","Billmyre RB","Applen Clancey S","Heitman J","Doering TL"],"additional_accession":[]},"is_claimable":false,"name":"5-fluorocytosine resistance is associated with hypermutation and alterations in capsule biosynthesis in Cryptococcus.","description":"Patients infected with the fungal pathogen Cryptococcus are most effectively treated with a combination of 5-fluorocytosine (5FC) and amphotericin B. 5FC acts as a prodrug, which is converted into toxic 5-fluorouracil (5FU) upon uptake into fungal cells. However, the pathogen frequently develops resistance through unclear mechanisms. Here we show that resistance to 5FC in Cryptococcus deuterogattii is acquired more frequently in isolates with defects in DNA mismatch repair that confer an elevated mutation rate. We use whole genome sequencing of 16 independent isolates to identify mutations associated with 5FC resistance in vitro. We find mutations in known resistance genes (FUR1 and FCY2) and in a gene UXS1, previously shown to encode an enzyme that converts UDP-glucuronic acid to UDP-xylo","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2026-04-12T23:50:01.223Z","creation":"2020-05-22T07:32:32Z"},"accession":"S-EPMC6949227","cross_references":{"pubmed":["31913284"],"doi":["10.1038/s41467-019-13890-z"]}}