ArticlePloS one2011
Paromomycin affects translation and vesicle-mediated trafficking as revealed by proteomics of paromomycin -susceptible -resistant Leishmania donovani.
Article in PloS one, 2011. 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, 111 citations in OpenAlex.
- Article
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- Multi-drug tolerance in Leishmania persister-like cells.Communications biology · 2026Article
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- CRISPR-Cas13b mediated gene knockdowns in Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2025Article
- Leishmaniases: Strategies in treatment development.Parasite (Paris, France) · 2025Review
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Antiprotozoal Natural Products from Endophytic Fungi Associated with Cacao and Coffee.Metabolites · 2024Article
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Synergistic Effects of Artesunate in Combination with Amphotericin B and Miltefosine againstAntibiotics (Basel, Switzerland) · 2024Article
- 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
- Unveiling drug-tolerant and persister-like cells inFrontiers in cellular and infection microbiology · 2023Article
- Treatment of Cutaneous Leishmaniasis and Insights into Species-Specific Responses: A Narrative Review.Infectious diseases and therapy · 2022Review
- Engineering and functional analysis of yeast with a monotypic 40S ribosome subunit.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Experimental Selection of Paromomycin Resistance inMicroorganisms · 2021Article
- SCRaMbLE: A Study of Its Robustness and Challenges through Enhancement of Hygromycin B Resistance in a Semi-Synthetic Yeast.Bioengineering (Basel, Switzerland) · 2021Article
- Activity of paromomycin against Leishmania amazonensis: Direct correlation between susceptibility in vitro and the treatment outcome in vivo.International journal for parasitology. Drugs and drug resistance · 2020Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Comparative mitochondrial proteomics of Leishmania tropica clinical isolates resistant and sensitive to meglumine antimoniate.Parasitology research · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis (VL) and is responsible for significant mortality and morbidity. Increasing resistance towards antimonial drugs poses a great challenge in chemotherapy of VL. Paromomycin is an aminoglycosidic antibiotic and is one of the drugs currently being used in the chemotherapy of cutaneous and visceral leishmaniasis. To understand the mode of action of this antibiotic at the molecular level, we have investigated the global proteome differences between the wild type AG83 strain and a paromomycin resistant (PRr) strain of L. donovani. Stable isotope labeling of amino acids in cell culture (SILAC) followed by quantitative mass spectrometry of the wild type AG83 strain and the paromomycin resistant (PRr) strain identified a total of 226 proteins at ≥ 95% confidence. Data analysis revealed upregulation of 29 proteins and down-regulation of 21 proteins in the PRr strain. Comparative proteomic analysis of the wild type and the paromomycin resistant strains showed upregulation of the ribosomal proteins in the resistant strain indicating role in translation. Elevated levels of glycolytic enzymes and stress proteins were also observed in the PRr strain. Most importantly, we observed upregulation of proteins that may have a role in intracellular survival and vesicular trafficking in the PRr strain. Furthermore, ultra-structural analysis by electron microscopy demonstrated increased number of vesicular vacuoles in PRr strain when compared to the wild-type strain. Drug affinity pull-down assay followed by mass spectrometery identified proteins in L. donovani wild type strain that were specifically and covalently bound to paromomycin. These results provide the first comprehensive insight into the mode of action and underlying mechanism of resistance to paromomycin in Leishmania donovani.
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