ArticlePLoS neglected tropical diseases2012
Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background.
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 52 papers.
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Who cites it
52 citing papers in PubMed, 95 citations in OpenAlex.
- Visceral leishmaniasis: an integrated review of resistance mechanisms, host immunometabolism, and next generation therapeutics.Inflammopharmacology · 2026Review
- Peptides as a Therapeutic Alternative Against Leishmaniasis: A Scoping Review.Chemical biology & drug design · 2026Article
- Identification of CβS and ODC antimony resistance markers in anthroponotic cutaneous leishmaniasis field isolates by gene expression profiling.Parasite epidemiology and control · 2025Article
- Potential selection of antimony and methotrexate cross-resistance in Leishmania infantum circulating strains.PLoS neglected tropical diseases · 2024Article
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- Potent Inhibitory Activity of Natural Product Anaephene B and Analogues againstMolecules (Basel, Switzerland) · 2023Article
- The paradigm of intracellular parasite survival and drug resistance in leishmanial parasite through genome plasticity and epigenetics: Perception and future perspective.Frontiers in cellular and infection microbiology · 2023Review
- Impact of collaborative actions ofParasitology · 2022Article
- The role of ATP-binding cassette transporter genes expression in treatment failure cutaneous leishmaniasis.AMB Express · 2022Article
- Treatment of Cutaneous Leishmaniasis and Insights into Species-Specific Responses: A Narrative Review.Infectious diseases and therapy · 2022Review
- Impact of Genetic Diversity and Genome Plasticity ofFrontiers in cellular and infection microbiology · 2022Review
- Antimony resistance mechanism in genetically different clinical isolates of Indian Kala-azar patients.Frontiers in cellular and infection microbiology · 2022Article
- Single-cell genome sequencing of protozoan parasites.Trends in parasitology · 2021Review
- Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony.Parasites & vectors · 2021Article
- Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony.Scientific reports · 2021Article
- Leishmanicidal Activity of Betulin Derivatives inMicroorganisms · 2021Article
- A Multi-Species Phenotypic Screening Assay for Leishmaniasis Drug Discovery Shows That Active Compounds Display a High Degree of Species-Specificity.Molecules (Basel, Switzerland) · 2020Article
- The Genetic Background Modulates the Evolution of Fluoroquinolone-Resistance in Mycobacterium tuberculosis.Molecular biology and evolution · 2020Article
- Review
- Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains.Antimicrobial agents and chemotherapy · 2019Article
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability.
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