ArticleCurrent genetics2009
PTR1-dependent synthesis of tetrahydrobiopterin contributes to oxidant susceptibility in the trypanosomatid protozoan parasite Leishmania major.
Article in Current genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Comparative metabolism of conjugated and unconjugated pterins in Crithidia, Leishmania and African trypanosomes.PLoS neglected tropical diseases · 2025Article
- Oxidative Stress and Survival ofExpert reviews in molecular medicine · 2025Review
- Design and Synthesis of New Anthranyl Phenylhydrazides: Antileishmanial Activity and Structure-Activity Relationship.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Translational reprogramming as a driver of antimony-drug resistance in Leishmania.Nature communications · 2023Article
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Combined gene deletion of dihydrofolate reductase-thymidylate synthase and pteridine reductase in Leishmania infantum.PLoS neglected tropical diseases · 2021Article
- The potential therapeutic role of PTR1 gene in non-healing anthroponotic cutaneous leishmaniasis due to Leishmania tropica.Journal of clinical laboratory analysis · 2021Article
- Antileishmanial activity evaluation of thiazolidine-2,4-dione against Leishmania infantum and Leishmania braziliensis.Parasitology research · 2020Article
- Leishmaniasis in humans: drug or vaccine therapy?Drug design, development and therapy · 2018Review
- LM14 defined medium enables continuous growth of Trypanosoma cruzi.BMC microbiology · 2014Article
- Deception and manipulation: the arms of leishmania, a successful parasite.Frontiers in immunology · 2014Review
- Article
- Dissecting the metabolic roles of pteridine reductase 1 in Trypanosoma brucei and Leishmania major.The Journal of biological chemistry · 2011Article
- State of the art in African trypanosome drug discovery.Current topics in medicinal chemistry · 2011Review
- Phenylalanine hydroxylase (PAH) from the lower eukaryote Leishmania major.Molecular and biochemical parasitology · 2011Article
- Trypanosoma brucei pteridine reductase 1 is essential for survival in vitro and for virulence in mice.Molecular microbiology · 2010Article
- Structure-based design of pteridine reductase inhibitors targeting African sleeping sickness and the leishmaniases.Journal of medicinal chemistry · 2010Article
- FolX and FolM are essential for tetrahydromonapterin synthesis in Escherichia coli and Pseudomonas aeruginosa.Journal of bacteriology · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Leishmania must survive oxidative stress, but lack many classical antioxidant enzymes and rely heavily on trypanothione-dependent pathways. We used forward genetic screens to recover loci mediating oxidant resistance via overexpression in Leishmania major, which identified pteridine reductase 1 (PTR1). Comparisons of isogenic lines showed ptr1 (-) null mutants were 18-fold more sensitive to H(2)O(2) than PTR1-overproducing lines, and significant three- to fivefold differences were seen with a broad panel of oxidant-inducing agents. The toxicities of simple nitric oxide generators and other drug classes (except antifolates) were unaffected by PTR1 levels. H(2)O(2) susceptibility could be modulated by exogenous biopterin but not folate, in a PTR1- but not dihydrofolate reductase-dependent manner, implicating H(4)B metabolism specifically. Neither H(2)O(2) consumption nor the level of intracellular oxidative stress was affected by PTR1 levels. Coupled with the fact that reduced pteridines are at least 100-fold less abundant than cellular thiols, these data argue strongly that reduced pteridines act through a mechanism other than scavenging. The ability of unconjugated pteridines to counter oxidative stress has implications to infectivity and response to chemotherapy. Since the intracellular pteridine levels of Leishmania can be readily manipulated, these organisms offer a powerful setting for the dissection of pteridine-dependent oxidant susceptibility in higher eukaryotes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.