ArticleInternational journal for parasitology. Drugs and drug resistance2017
Transcriptome profiling identifies genes/pathways associated with experimental resistance to paromomycin in Leishmania donovani.
Article in International journal for parasitology. Drugs and drug resistance, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Unravelling drug resistance in leishmaniasis: genomic adaptations and emerging therapies.Frontiers in molecular biosciences · 2025Review
- Molecular Mechanisms of Drug Resistance inPathogens (Basel, Switzerland) · 2024Review
- Translational reprogramming as a driver of antimony-drug resistance in Leishmania.Nature communications · 2023Article
- Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani.Parasitology research · 2022Article
- Transcriptome Analysis of Intracellular Amastigotes of ClinicalMicroorganisms · 2022Article
- Identification of 2-arylquinazolines with alkyl-polyamine motifs as potent antileishmanial agents: synthesis and biological evaluation studies.RSC medicinal chemistry · 2022Article
- Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony.Parasites & vectors · 2021Article
- Experimental Selection of Paromomycin Resistance inMicroorganisms · 2021Article
- Involvement ofFrontiers in cellular and infection microbiology · 2021Review
- Article
- High Throughput Approaches to Unravel the Mechanism of Action of a New Vanadium-Based Compound againstBioinorganic chemistry and applications · 2020Article
- Identifying miltefosine-resistant key genes in protein-protein interactions network and experimental verification in Iranian Leishmania major.Molecular biology reports · 2019Article
- Artemisinin-resistant Leishmania parasite modulates host cell defense mechanism and exhibits altered expression of unfolded protein response genes.Parasitology research · 2019Article
- Complete assembly of the Leishmania donovani (HU3 strain) genome and transcriptome annotation.Scientific reports · 2019Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Widespread resistance towards antimony and reports of relapses following miltefosine treatment has severely affected the management of visceral leishmaniasis (VL) in the Indian subcontinent. Paromomycin (PMM), an aminoglycoside antibiotic, has been licensed for VL treatment in India in 2007. Although its use is still restricted in the field, unraveling the molecular mechanism of resistance towards PMM is the key to preserve the drug. In this study, PMM resistant lines were selected up to 100 μM of PMM in three distinct field isolates of Leishmania donovani at promastigote stage. The resistance induced at promastigote level was also evident in amastigotes which showed 6 fold decreases in PMM susceptibility. Comparative transcriptome profiling of PMM resistant (PMM-R) and the corresponding PMM sensitive (PMM-S) parasites revealed modulated expression of 500 genes (1.5 fold cut off) in PMM-R parasites. Selected genes were validated for their modulated expression by quantitative real-time PCR. Functional classification and pathway analysis of modulated genes indicated probable adaptations in drug resistant lines which included a) reduced oxidative phosphorylation; b) increased glycosomal succinate fermentation and substrate level phosphorylation; c) dependency on lipids and amino acids for energy generation; d) reduced DNA synthesis and increased DNA damage repair and e) decreased protein synthesis and degradation. Interestingly, PMM-R parasites showed a marked increase in PMM susceptibility in presence of verapamil and amlodipine, antagonists of Ca
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