ArticleInternational journal for parasitology. Drugs and drug resistance2014
Untargeted metabolomic analysis of miltefosine action in Leishmania infantum reveals changes to the internal lipid metabolism.
Article in International journal for parasitology. Drugs and drug resistance, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 81 citations in OpenAlex.
- Miltefosine and emerging Leishmania (Mundinia) in Southeast Asia: Molecular insights, therapeutic challenges, and future strategic implementation.PLoS neglected tropical diseases · 2026Review
- CRISPR-Cas13b mediated gene knockdowns in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2025Article
- Interventions for Neglected Diseases Caused by Kinetoplastid Parasites: A One Health Approach to Drug Discovery, Development, and Deployment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Metabolomics analysis of visceral leishmaniasis based on urine of golden hamsters.Parasites & vectors · 2023Article
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- The Antileishmanial Activity of Eugenol Associated with Lipid Storage Reduction Rather Than Membrane Properties Alterations.Molecules (Basel, Switzerland) · 2023Article
- Effect of Clindamycin on Intestinal Microbiome and Miltefosine Pharmacology in Hamsters Infected withAntibiotics (Basel, Switzerland) · 2023Article
- New insights in photodynamic inactivation of Leishmania amazonensis: A focus on lipidomics and resistance.PloS one · 2023Article
- Exploring direct and indirect targets of current antileishmanial drugs using a novel thermal proteomics profiling approach.Frontiers in cellular and infection microbiology · 2022Article
- The lipidome ofFrontiers in cellular and infection microbiology · 2022Article
- Editorial: Signaling in stress sensing and resistance in parasitic protozoa.Frontiers in cellular and infection microbiology · 2022Article
- Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused byPathogens (Basel, Switzerland) · 2021Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Sex-specific hippocampal metabolic signatures at the onset of systemic inflammation with lipopolysaccharide in the APPswe/PS1dE9 mouse model of Alzheimer's disease.Brain, behavior, and immunity · 2020Article
- Synthesis of a novel brominated vinylic fatty acid with antileishmanial activity that effectively inhibits thePure and applied chemistry. Chimie pure et appliquee · 2019Article
- Synergistic combination of alkylphosphocholines with peptaibols in targeting Leishmania infantum in vitro.International journal for parasitology. Drugs and drug resistance · 2018Article
- High-throughput Cos-Seq screen with intracellular Leishmania infantum for the discovery of novel drug-resistance mechanisms.International journal for parasitology. Drugs and drug resistance · 2018Article
- Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine.Antimicrobial agents and chemotherapy · 2018Article
- Comparative mass spectrometry-based metabolomics strategies for the investigation of microbial secondary metabolites.Natural product reports · 2017Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
There are many theories as to the mode of action of miltefosine against Leishmania including alterations to the membrane lipid content, induction of apoptosis and modulation of macrophage responses. Here we perform untargeted metabolomics to elucidate the metabolic changes involved in miltefosine action. Over 800 metabolites were detected, 10% of which were significantly altered after 3.75 h. Many of the changes related to an increase in alkane fragment and sugar release. Fragment release is synchronised with reactive oxygen species production, but native membrane phospholipids remain intact. Signs of DNA damage were also detected as were changes to the levels of some thiols and polyamines. After 5 h of miltefosine treatment the cells showed depleted levels of most metabolites, indicating that the cells' outer membrane integrity had become compromised and internal metabolites were escaping upon cell death. In miltefosine resistant cells, the drug was not internalised and the changes to the internal metabolite levels were not seen. In contrast, cells resistant to antimony (SbIII) had similar corresponding alterations to the levels of internal metabolites as wild-type cells. A detailed knowledge of the mode of action of miltefosine will be important to inform the design of combination therapies to combat leishmaniasis, something that the research community should be prioritising in the coming years.
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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.