ArticleParasitology research2014
Comparative transcript expression analysis of miltefosine-sensitive and miltefosine-resistant Leishmania donovani.
Article in Parasitology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Miltefosine and emerging Leishmania (Mundinia) in Southeast Asia: Molecular insights, therapeutic challenges, and future strategic implementation.PLoS neglected tropical diseases · 2026Review
- Putrescine Depletion inPathogens (Basel, Switzerland) · 2025Article
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Article
- 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
- Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022Review
- Article
- Modeling and simulation study to identify threonine synthase as possible drug target in Leishmania major.Molecular diversity · 2021Article
- Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Identifying miltefosine-resistant key genes in protein-protein interactions network and experimental verification in Iranian Leishmania major.Molecular biology reports · 2019Article
- Lipase Precursor-Like Protein Promotes Miltefosine Tolerance in Leishmania donovani by Enhancing Parasite Infectivity and Eliciting Anti-inflammatory Responses in Host Macrophages.Antimicrobial agents and chemotherapy · 2018Article
- Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.PLoS neglected tropical diseases · 2017Review
- Transcriptome profiling identifies genes/pathways associated with experimental resistance to paromomycin in Leishmania donovani.International journal for parasitology. Drugs and drug resistance · 2017Article
- Mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets in the antileishmanial and anticancer activities of ether lipid edelfosine.PLoS neglected tropical diseases · 2017Article
- Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress.PLoS neglected tropical diseases · 2017Article
- Laboratory confirmed miltefosine resistant cases of visceral leishmaniasis from India.Parasites & vectors · 2017Article
- Drug resistance in eukaryotic microorganisms.Nature microbiology · 2016Review
- In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterization.Molecular microbiology · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania donovani is the causative agent of anthroponotic visceral leishmaniasis in the Indian subcontinent. Oral miltefosine therapy has recently replaced antimonials in endemic areas. However, the drug is at risk of emergence of resistance due to unrestricted use, and, already, there are indications towards decline in treatment efficacy. Hence, understanding the mechanism of miltefosine resistance in the parasite is crucial. We employed genomic microarray analysis to compare the gene expression patterns of miltefosine-resistant and miltefosine-sensitive L. donovani. Three hundred eleven genes, representing ∼3.9% of the total Leishmania genome, belonging to various functional categories including metabolic pathways, transporters, and cellular components, were differentially expressed in miltefosine-resistant parasite. Results in the present study highlighted the probable mechanisms by which the parasite sustains miltefosine pressure including (1) compromised DNA replication/repair mechanism, (2) reduced protein synthesis and degradation, (3) altered energy utilization via increased lipid degradation, (4) increased ABC 1-mediated drug efflux, and (5) increased antioxidant defense mechanism via elevated trypanothione metabolism. The study provided the comprehensive insight into the underlying mechanism of miltefosine resistance in L. donovani that may be useful to design strategies to increase lifespan of this important oral antileishmanial drug.
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