ArticleAntimicrobial agents and chemotherapy2005
Alteration of fatty acid and sterol metabolism in miltefosine-resistant Leishmania donovani promastigotes and consequences for drug-membrane interactions.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- Pooled it
- Miltefosine and emerging Leishmania (Mundinia) in Southeast Asia: Molecular insights, therapeutic challenges, and future strategic implementation.PLoS neglected tropical diseases · 2026Review
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Synergistic Effects of Artesunate in Combination with Amphotericin B and Miltefosine againstAntibiotics (Basel, Switzerland) · 2024Article
- Computational and Experimental Approaches Towards Understanding the Role of ATG8 in Autophagy: A Therapeutic Paradigm in Leishmaniasis.The protein journal · 2024Article
- Treatment and Healing of Leishmaniasis in a Wolf in Semi-Captivity Regime from an Educational Center of Zamora Province (Spain).Animals : an open access journal from MDPI · 2024Article
- Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular CaBiomolecules · 2024Review
- AnSoft matter · 2023Article
- Fatty Acid Composition and Metabolism inInternational journal of molecular sciences · 2023Review
- New insights in photodynamic inactivation of Leishmania amazonensis: A focus on lipidomics and resistance.PloS one · 2023Article
- Fatty Acid Profiles ofPathogens (Basel, Switzerland) · 2022Article
- Miltefosine enhances infectivity of a miltefosine-resistant Leishmania infantum strain by attenuating its innate immune recognition.PLoS neglected tropical diseases · 2021Article
- Article
- Drug combinations as effective anti-leishmanials against drug resistantRSC medicinal chemistry · 2020Article
- Structure and Antiparasitic Activity Relationship of Alkylphosphocholine Analogues againstMicroorganisms · 2020Article
- Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites.PLoS neglected tropical diseases · 2020Article
- Lipid profile of Trichinella papuae muscle-stage larvae.Scientific reports · 2020Article
- Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania.Nature communications · 2019Article
- Impaired development of a miltefosine-resistant Leishmania infantum strain in the sand fly vectors Phlebotomus perniciosus and Lutzomyia longipalpis.International journal for parasitology. Drugs and drug resistance · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active drug approved for the treatment of visceral leishmaniasis. In order to investigate the biochemical modifications occurring in HePC-resistant (HePC-R) Leishmania donovani promastigotes, taking into account the lipid nature of HePC, we investigated their fatty acid and sterol metabolisms. We found that the content of unsaturated phospholipid alkyl chains was lower in HePC-R parasite plasma membranes than in those of the wild type, suggesting a lower fluidity of HePC-R parasite membranes. We also demonstrated that HePC insertion within an external monolayer was more difficult when the proportion of unsaturated phospholipids decreased, rendering the HePC interaction with the external monolayer of HePC-R parasites more difficult. Furthermore, HePC-R parasite membranes displayed a higher content of short alkyl chain fatty acids, suggesting a partial inactivation of the fatty acid elongation enzyme system in HePC-R parasites. Sterol biosynthesis was found to be modified in HePC-R parasites, since the 24-alkylated sterol content was halved in HePC-R parasites; however, this modification was not related to HePC sensitivity. In conclusion, HePC resistance affects three lipid biochemical pathways: fatty acid elongation, the desaturase system responsible for fatty acid alkyl chain unsaturation, and the C-24-alkylation of sterols.
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Registered trials
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.