ArticleMolecular microbiology2016
In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterization.
Article in Molecular microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
- Miltefosine and emerging Leishmania (Mundinia) in Southeast Asia: Molecular insights, therapeutic challenges, and future strategic implementation.PLoS neglected tropical diseases · 2026Review
- Multi-drug tolerance in Leishmania persister-like cells.Communications biology · 2026Article
- Genome analyses of amphotericin B-susceptible and -resistant strains ofCurrent research in parasitology & vector-borne diseases · 2025Article
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Article
- The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress.EMBO reports · 2023Article
- 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
- Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment ofInternational journal of molecular sciences · 2023Article
- New insights in photodynamic inactivation of Leishmania amazonensis: A focus on lipidomics and resistance.PloS one · 2023Article
- Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani.Parasitology research · 2022Article
- Selective Anti-Leishmanial Strathclyde Minor Groove Binders Using an N-Oxide Tail-Group Modification.International journal of molecular sciences · 2022Article
- Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response.PLoS neglected tropical diseases · 2022Article
- Article
- High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy in Leishmania donovani.Nucleic acids research · 2022Article
- Genome deletions to overcome the directed loss of gene function inFrontiers in cellular and infection microbiology · 2022Article
- Article
- Metabolite Biomarkers ofCells · 2021Article
- Ros3 (Lem3p/CDC50) Gene Dosage Is Implicated in Miltefosine Susceptibility inACS infectious diseases · 2021Article
- Drug-Induced Lipid Remodeling inMicroorganisms · 2021Article
- Tryp-ing Up Metabolism: Role of Metabolic Adaptations in Kinetoplastid Disease Pathogenesis.Infection and immunity · 2021Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
Abstract
In this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (MIL) resistance in two clinically derived Leishmania donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain Sb-S; and antimony resistant Sb-R). MIL-R was easily induced in both strains using the promastigote-stage, but a significant increase in MIL-R in the intracellular amastigote compared to the corresponding wild-type did not occur until promastigotes had adapted to 12.2 μM MIL. A variety of common and strain-specific genetic changes were discovered in MIL-adapted parasites, including deletions at the LdMT transporter gene, single-base mutations and changes in somy. The most obvious lipid changes in MIL-R promastigotes occurred to phosphatidylcholines and lysophosphatidylcholines and results indicate that the Kennedy pathway is involved in MIL resistance. The inherent Sb resistance of the parasite had an impact on the changes that occurred in MIL-R parasites, with more genetic changes occurring in Sb-R compared with Sb-S parasites. Initial interpretation of the changes identified in this study does not support synergies with Sb-R in the mechanisms of MIL resistance, though this requires an enhanced understanding of the parasite's biochemical pathways and how they are genetically regulated to be verified fully.
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