ArticlePLoS neglected tropical diseases2013
Gene amplification and point mutations in pyrimidine metabolic genes in 5-fluorouracil resistant Leishmania infantum.
Article in PLoS neglected tropical diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
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- Decreased glutamate transport in acivicin resistant Leishmania tarentolae.PLoS neglected tropical diseases · 2021Article
- Three different mutations in the DNA topoisomerase 1B in Leishmania infantum contribute to resistance to antitumor drug topotecan.Parasites & vectors · 2021Article
- Combined gene deletion of dihydrofolate reductase-thymidylate synthase and pteridine reductase in Leishmania infantum.PLoS neglected tropical diseases · 2021Article
- MRPA-independent mechanisms of antimony resistance in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2020Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Comparative lipidomics of 5-Fluorouracil-sensitive and -resistant colorectal cancer cells reveals altered sphingomyelin and ceramide controlled by acid sphingomyelinase (SMPD1).Scientific reports · 2020Article
- The mutational footprints of cancer therapies.Nature genetics · 2019Article
- Resistance of Leishmania infantum to allopurinol is associated with chromosome and gene copy number variations including decrease in the S-adenosylmethionine synthetase (METK) gene copy number.International journal for parasitology. Drugs and drug resistance · 2018Article
- Fresh insights into the pyrimidine metabolism in the trypanosomatids.Parasites & vectors · 2018Review
- Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy.International journal for parasitology. Drugs and drug resistance · 2017Article
- Comparative genomics of Tunisian Leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2017Article
- Different Mutations in a P-type ATPase Transporter in Leishmania Parasites are Associated with Cross-resistance to Two Leading Drugs by Distinct Mechanisms.PLoS neglected tropical diseases · 2016Article
- Plasticity of theF1000Research · 2016Review
- Drug resistance analysis by next generation sequencing in Leishmania.International journal for parasitology. Drugs and drug resistance · 2015Review
- Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis.PLoS neglected tropical diseases · 2015Article
- Quantitative proteomic analysis of amphotericin B resistance in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe human protozoan parasites Leishmania are prototrophic for pyrimidines with the ability of both de novo biosynthesis and uptake of pyrimidines. METHODOLOGY/PRINCIPAL
findingsFive independent L. infantum mutants were selected for resistance to the pyrimidine analogue 5-fluorouracil (5-FU) in the hope to better understand the metabolism of pyrimidine in Leishmania. Analysis of the 5-FU mutants by comparative genomic hybridization and whole genome sequencing revealed in selected mutants the amplification of DHFR-TS and a deletion of part of chromosome 10. Point mutations in uracil phosphorybosyl transferase (UPRT), thymidine kinase (TK) and uridine phosphorylase (UP) were also observed in three individual resistant mutants. Transfection experiments confirmed that these point mutations were responsible for 5-FU resistance. Transport studies revealed that one resistant mutant was defective for uracil and 5-FU import. CONCLUSION/SIGNIFICANCE: This study provided further insights in pyrimidine metabolism in Leishmania and confirmed that multiple mutations can co-exist and lead to resistance in Leishmania.
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