ArticlePLoS neglected tropical diseases2012
Leishmania donovani develops resistance to drug combinations.
Article in PLoS neglected tropical diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Differentially modulated proteins associated with Leishmaniasis-a systematic review of in-vivo and in-vitro studies.Molecular biology reports · 2020Pooled it
- Synthesis and preliminary evaluation of novel compounds that demonstrate broad host-directed anti-leishmanial activity.PLoS neglected tropical diseases · 2026Article
- Leishmaniasis: pathogenesis, host immunity, and the evolving landscape of immunotherapy and immunochemotherapy.Frontiers in microbiology · 2026Review
- Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area.Parasites & vectors · 2025Article
- Discovery of Host-Directed Small Molecules with Broad Anti-Leishmanial Efficacy.bioRxiv : the preprint server for biology · 2025Article
- Antitrypanosomal and Antileishmanial Activities ofMolecules (Basel, Switzerland) · 2025Article
- Leishmaniases: Strategies in treatment development.Parasite (Paris, France) · 2025Review
- Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions.PLoS neglected tropical diseases · 2024Article
- A molecular signature for IL-10-producing Th1 cells in protozoan parasitic diseases.JCI insight · 2023Article
- Article
- Amphotericin B resistance correlates with increased fitnessFrontiers in microbiology · 2023Article
- Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B.Tropical medicine and infectious disease · 2022Article
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Impact of Genetic Diversity and Genome Plasticity ofFrontiers in cellular and infection microbiology · 2022Review
- The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.Frontiers in cellular and infection microbiology · 2022Article
- Article
- A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among ClinicalFrontiers in cellular and infection microbiology · 2021Article
- Evaluation of the Pharmacophoric Role of the O-O Bond in Synthetic Antileishmanial Compounds: Comparison between 1,2-Dioxanes and Tetrahydropyrans.Journal of medicinal chemistry · 2020Article
- Drug combinations as effective anti-leishmanials against drug resistantRSC medicinal chemistry · 2020Article
- In-depth comparison of cell-based methodological approaches to determine drug susceptibility of visceral Leishmania isolates.PLoS neglected tropical diseases · 2019Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug combinations for the treatment of leishmaniasis represent a promising and challenging chemotherapeutic strategy that has recently been implemented in different endemic areas. However, the vast majority of studies undertaken to date have ignored the potential risk that Leishmania parasites could develop resistance to the different drugs used in such combinations. As a result, this study was designed to elucidate the ability of Leishmania donovani to develop experimental resistance to anti-leishmanial drug combinations. The induction of resistance to amphotericin B/miltefosine, amphotericin B/paromomycin, amphotericin B/Sb(III), miltefosine/paromomycin, and Sb(III)/paromomycin was determined using a step-wise adaptation process to increasing drug concentrations. Intracellular amastigotes resistant to these drug combinations were obtained from resistant L. donovani promastigote forms, and the thiol and ATP levels and the mitochondrial membrane potential of the resistant lines were analysed. Resistance to drug combinations was obtained after 10 weeks and remained in the intracellular amastigotes. Additionally, this resistance proved to be unstable. More importantly, we observed that promastigotes/amastigotes resistant to one drug combination showed a marked cross-resistant profile to other anti-leishmanial drugs. Additionally, the thiol levels increased in resistant lines that remained protected against the drug-induced loss of ATP and mitochondrial membrane potential. We have therefore demonstrated that different resistance patterns can be obtained in L. donovani depending upon the drug combinations used. Resistance to the combinations miltefosine/paromomycin and Sb(III)/paromomycin is easily obtained experimentally. These results have been validated in intracellular amastigotes, and have important relevance for ensuring the long-term efficacy of drug combinations.
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Registered trials
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