ArticleAntimicrobial agents and chemotherapy2003
Leishmania donovani resistance to miltefosine involves a defective inward translocation of the drug.
Article in Antimicrobial agents and chemotherapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed.
- Peptide-Enabled Nanoplatforms for Malaria and Leishmaniasis: From Intracellular Targeting to Translational Diagnostic Perspectives.ChemMedChem · 2026Review
- Dicentrine, an Aporphine Alkaloid From Ocotea langsdorffii, Induces Mitochondrial Dysfunction and Oxidative Stress in Leishmania (L.) infantum.Chemistry & biodiversity · 2026Article
- Crusted, Chronic, and Confusing.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- CRISPR-Cas13b mediated gene knockdowns in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2025Article
- Repositioning of moxidectin: a promising approach in cutaneous leishmaniasis therapy.Parasite (Paris, France) · 2025Article
- Evaluation of Beauvericin's activity and mode of action against all life stages ofFrontiers in cellular and infection microbiology · 2025Article
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- Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host.Pathogens (Basel, Switzerland) · 2023Review
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- Antileishmanial Drug Discovery and Development: Time to Reset the Model?Microorganisms · 2021Review
- Miltefosine enhances infectivity of a miltefosine-resistant Leishmania infantum strain by attenuating its innate immune recognition.PLoS neglected tropical diseases · 2021Article
- Ros3 (Lem3p/CDC50) Gene Dosage Is Implicated in Miltefosine Susceptibility inACS infectious diseases · 2021Article
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- Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance.Antimicrobial agents and chemotherapy · 2020Article
- Drug combinations as effective anti-leishmanials against drug resistantRSC medicinal chemistry · 2020Article
- Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection.Parasites & vectors · 2020Article
- Investigation of the pathways related to intrinsic miltefosine tolerance in Leishmania (Viannia) braziliensis clinical isolates reveals differences in drug uptake.International journal for parasitology. Drugs and drug resistance · 2019Article
- Immunosuppression of Syrian golden hamsters accelerates relapse but not the emergence of resistance in Leishmania infantum following recurrent miltefosine pressure.International journal for parasitology. Drugs and drug resistance · 2019Article
- P-type transport ATPases in Leishmania and Trypanosoma.Parasite (Paris, France) · 2019Review
11 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
Miltefosine (hexadecylphosphocholine [HePC]) is the first drug approved for the oral treatment of visceral leishmaniasis. As part of a study on the mechanisms of action of this drug and on the rates of resistance to this drug, we have been working in vitro with an Leishmania donovani line that was previously shown to be 15-fold more resistant to HePC. We have studied the accumulation of [(14)C]HePC by L. donovani promastigotes and have found a drastic reduction (>95%) in the ability of the resistant line to internalize the drug. Binding of HePC to the plasma membrane and drug efflux from preloaded cells were similar in both drug-sensitive and -resistant lines, and no [(14)C]HePC metabolism was evident in either line. Resistant parasites were also unable to take up other short-chain phospholipid analogs, independently of their polar head group, even though endocytosis remained unaltered. Finally, HePC uptake was temperature and energy dependent and sensitive to the thiol-reactive agent N-ethylmaleimide. We propose that inward translocation of a short-chain phospholipid across the plasma membrane may exist in Leishmania promastigotes and that such activity is defective in the resistant line.
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