ArticleAntimicrobial agents and chemotherapy2014
Elucidation of cellular mechanisms involved in experimental paromomycin resistance in Leishmania donovani.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 70 citations in OpenAlex.
- Insights into drug resistance inADMET & DMPK · 2026Review
- Deciphering Host-Parasite Interplay inACS infectious diseases · 2024Article
- Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.ACS omega · 2024Review
- Antimony resistance and gene expression inParasitology · 2024Review
- Label-Free Mass Spectrometry Proteomics Reveals Different Pathways Modulated in THP-1 Cells Infected with Therapeutic Failure and Drug ResistanceACS infectious diseases · 2023Article
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Antileishmanial Drug Discovery and Development: Time to Reset the Model?Microorganisms · 2021Review
- Experimental Selection of Paromomycin Resistance inMicroorganisms · 2021Article
- Perspectives From Systems Biology to Improve Knowledge ofFrontiers in cellular and infection microbiology · 2021Article
- A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among ClinicalFrontiers in cellular and infection microbiology · 2021Article
- Involvement ofFrontiers in cellular and infection microbiology · 2021Review
- Article
- LmjF.22.0810 fromBiomedicines · 2020Article
- MicroRNA exporter HuR clears the internalized pathogens by promoting pro-inflammatory response in infected macrophages.EMBO molecular medicine · 2020Article
- Molecular docking analysis of an isoflavone derivative with the protein phosphatase 1 from Leishmania donovani.Bioinformation · 2020Article
- Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains.Antimicrobial agents and chemotherapy · 2019Article
- Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania.Nature communications · 2019Article
- In-depth comparison of cell-based methodological approaches to determine drug susceptibility of visceral Leishmania isolates.PLoS neglected tropical diseases · 2019Article
- An Overview of Drug Resistance in Protozoal Diseases.International journal of molecular sciences · 2019Review
- The Novel Serine/Threonine Protein Kinase LmjF.22.0810 fromBiomolecules · 2019Article
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania donovani is the causative agent of the potentially fatal disease visceral leishmaniasis (VL). Chemotherapeutic options available to treat VL are limited and often face parasite resistance, inconsistent efficacy, and toxic side effects. Paromomycin (PMM) was recently introduced to treat VL as a monotherapy and in combination therapy. It is vital to understand the mechanisms of PMM resistance to safeguard the drug. In the present study, we utilized experimentally generated PMM-resistant L. donovani to elucidate the mechanisms of resistance and parasite biology. We found increased membrane fluidity accompanied by decreased intracellular drug accumulation in the PMM-resistant parasites. There were marked increases in gene expression of ATP-binding cassette (ABC) transporters (MDR1 and MRPA) and protein phosphatase 2A that evince increased drug efflux. Further, evaluation of parasite tolerance toward host leishmanicidal mechanisms revealed PMM-resistant parasites as being more tolerant to nitrosative stress at the promastigote and amastigote stages. The PMM-resistant parasites also predicted a better survival capacity, as indicated by resistance to complement-mediated lysis and increased stimulation of host interleukin-10 (IL-10) expression. The susceptibilities of PMM-resistant isolates to other antileishmanial agents (sodium antimony gluconate and miltefosine) remained unchanged. The data implicated the roles of altered membrane fluidity, decreased drug accumulation, increased expression of ABC transporters, and greater tolerance of parasites to host defense mechanisms in conferring PMM resistance in Leishmania.
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