ArticleInfection and immunity2017
Arginase Is Essential for Survival of Leishmania donovani Promastigotes but Not Intracellular Amastigotes.
Article in Infection and immunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 79 citations in OpenAlex.
- From Forest Floor to Therapeutic Candidate: Amanita princeps Corner & Bas, 1962 Counters Visceral Leishmaniasis via the NO-Arginase Axis and Mitochondrial Pathway.Cell biochemistry and biophysics · 2026Article
- The arginase-polyamine signaling axis in immune cells: Implications for immune modulation and host-pathogen interactions.iScience · 2026Review
- Putrescine Depletion inPathogens (Basel, Switzerland) · 2025Article
- Article
- Molecular Characterization of Sterol C4-Methyl Oxidase inInternational journal of molecular sciences · 2024Article
- Polyamine Metabolism for Drug Intervention in Trypanosomatids.Pathogens (Basel, Switzerland) · 2024Review
- Early Leishmania infectivity depends on miR-372/373/520d family-mediated reprogramming of polyamines metabolism in THP-1-derived macrophages.Scientific reports · 2024Article
- State-of-the-art Review on the Antiparasitic Activity of Benzimidazolebased Derivatives: Facing Malaria, Leishmaniasis, and Trypanosomiasis.Current medicinal chemistry · 2024Review
- Selene-Ethylenelacticamides andPathogens (Basel, Switzerland) · 2023Article
- Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps.Research and reports in tropical medicine · 2023Review
- Unwinding the mechanism of macrophage repolarization potential ofFrontiers in cellular and infection microbiology · 2023Article
- Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection.PloS one · 2023Article
- The pathogenicity and virulence of Leishmania - interplay of virulence factors with host defenses.Virulence · 2022Review
- Metabolic Pathways ofPharmaceutics · 2022Review
- Anti-leishmanial activity ofParasite epidemiology and control · 2022Article
- Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022Review
- Immunogenic properties of empty pcDNA3 plasmid against zoonotic cutaneous leishmaniasis in mice.PloS one · 2022Article
- Ku80 is involved in telomere maintenance but dispensable for genomic stability in Leishmania mexicana.PLoS neglected tropical diseases · 2021Article
- Hide-and-Seek: A Game Played between Parasitic Protists and Their Hosts.Microorganisms · 2021Review
- Metabolomic Reprogramming of C57BL/6-Macrophages during Early Infection withInternational journal of molecular sciences · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Studies of Leishmania donovani have shown that both ornithine decarboxylase and spermidine synthase, two enzymes of the polyamine biosynthetic pathway, are critical for promastigote proliferation and required for maximum infection in mice. However, the importance of arginase (ARG), the first enzyme of the polyamine pathway in Leishmania, has not been analyzed in L. donovani To test ARG function in intact parasites, we generated Δarg null mutants in L. donovani and evaluated their ability to proliferate in vitro and trigger infections in mice. The Δarg knockout was incapable of growth in the absence of polyamine supplementation, but the auxotrophic phenotype could be bypassed by addition of either millimolar concentrations of ornithine or micromolar concentrations of putrescine or by complementation with either glycosomal or cytosolic versions of ARG. Spermidine supplementation of the medium did not circumvent the polyamine auxotrophy of the Δarg line. Although ARG was found to be essential for ornithine and polyamine synthesis, ornithine decarboxylase appeared to be the rate-limiting enzyme for polyamine production. Mouse infectivity studies revealed that the Δarg lesion reduced parasite burdens in livers by an order of magnitude but had little impact on the numbers of parasites recovered from spleens. Thus, ARG is essential for proliferation of promastigotes but not intracellular amastigotes. Coupled with previous studies, these data support a model in which L. donovani amastigotes readily salvage ornithine and have some access to host spermidine pools, while host putrescine appears to be unavailable for salvage by the parasite.
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Registered trials
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