PXD044249-1

PXD044249 is an original dataset announced via ProteomeXchange.

Title	Novel genetic mutations in pyrimidine salvage pathway enzymes from Cryptococcus neoformans contribute to reduced susceptibility against 5-fluorocytosine
Description	The most common cause of cryptococcal meningitis is Cryptococcus neoformans. The addition of 5-fluorocytosine to the treatment of patient with this potentially fatal infection significantly improves disease outcome. However, developing resistance to this drug is a serious problem in patient management. In this study, we investigated the molecular mechanisms causing 5-FC resistance in three clinical isolates of C. neoformans using genomic and proteomic approaches. Our findings show that genetic alterations in genes involved in the pyrimidine salvage pathway caused 5-FC resistance in these isolates. Specifically, one isolate had a missense mutation (E64G) in the uracil phosphoribosyl transferase gene (FUR1), another isolate had a large deletion spanning the cytosine deaminase gene (FCY1), and the third isolate had a point mutation in the same gene leading to a truncated protein at amino acid 164 (STOPW164*). Proteomic data confirmed that the genetic changes led to the absence or decreased the amount of the enzymes in the 5-FC resistant isolates. Transformation experiments confirmed that the genetic changes ultimately affected 5-FC susceptibility, providing further evidence of the effect of the genetic changes on 5-FC susceptibility.
HostingRepository	PRIDE
AnnounceDate	2024-07-30
AnnouncementXML	Submission_2024-07-29_17:29:22.358.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alfredo Cabrera-Orefice
SpeciesList	scientific name: Cryptococcus neoformans var. grubii; NCBI TaxID: 178876; scientific name: Cryptococcus neoformans var. neoformans; NCBI TaxID: 40410;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-31 22:24:17	ID requested
⏵ 1	2024-07-29 17:29:22	announced
2	2024-10-22 06:51:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: pyrimidine salvage pathway, proteomics,Cryptococcus neoformans, resistance, 5-fluorocytosine

Paul Verweij
contact affiliation	Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands
contact email	Paul.Verweij@radboudumc.nl
lab head
Alfredo Cabrera-Orefice
contact affiliation	Goethe University Frankfurt
contact email	alfredbiomed@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044249
     1. Label: PRIDE project
     2. Name: Novel genetic mutations in pyrimidine salvage pathway enzymes from Cryptococcus neoformans contribute to reduced susceptibility against 5-fluorocytosine