ArticleInternational journal for parasitology. Drugs and drug resistance2017
Genomic analysis of Isometamidium Chloride resistance in Trypanosoma congolense.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- A cell surface transporter mediates phenanthridine resistance in African trypanosomes.npj antimicrobials and resistance · 2026Article
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Identification of Potential Vectors and Species Density of Tsetse Fly, Prevalence, and Genetic Diversity of Drug-Resistant Trypanosomes in Kenya.Pathogens (Basel, Switzerland) · 2025Article
- Drug resistance in animal trypanosomiases: Epidemiology, mechanisms and control strategies.International journal for parasitology. Drugs and drug resistance · 2024Review
- Tractable Quinolone Hydrazides Exhibiting Sub-Micromolar and Broad Spectrum Antitrypanosomal Activities.ChemMedChem · 2024Article
- Effects of Synthetic Ligustrazine-Based Chalcone Derivatives onMolecules (Basel, Switzerland) · 2023Article
- Trypanosoma Congolense Resistant to Trypanocidal Drugs Homidium and Diminazene and their Molecular Characterization in Lambwe, Kenya.Acta parasitologica · 2023Article
- Four layer multi-omics reveals molecular responses to aneuploidy in Leishmania.PLoS pathogens · 2022Article
- Current Treatments to Control African Trypanosomiasis and One Health Perspective.Microorganisms · 2022Review
- Investigation on Prevalence of Canine Trypanosomiasis in the Conservation Areas of Bwindi-Mgahinga and Queen Elizabeth in Western Uganda.Journal of parasitology research · 2022Article
- rKOMICS: an R package for processing mitochondrial minicircle assemblies in population-scale genome projects.BMC bioinformatics · 2021Article
- Revisiting the heterogeneous global genomic population structure ofMicrobial genomics · 2021Article
- Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition.PLoS pathogens · 2021Article
- Reliable, scalable functional genetics in bloodstream-form Trypanosoma congolense in vitro and in vivo.PLoS pathogens · 2021Article
- An African Canine Trypanosomosis Case Import: Is There a Possibility of Creating a Secondary Focus ofPathogens (Basel, Switzerland) · 2020Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Article
- Genomic Diversification, Structural Plasticity, and Hybridization inFrontiers in cellular and infection microbiology · 2020Article
- Characterization and phylogenetic analysis of multidrug-resistant protein - encoding genes inVeterinary world · 2019Article
- Major changes in chromosomal somy, gene expression and gene dosage driven by SbScientific reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Isometamidium Chloride (ISM) is one of the principal drugs used to counteract Trypanosoma congolense infection in livestock, both as a prophylactic as well as a curative treatment. However, numerous cases of ISM resistance have been reported in different African regions, representing a significant constraint in the battle against Animal African Trypanosomiasis. In order to identify genetic signatures associated with ISM resistance in T. congolense, the sensitive strain MSOROM7 was selected for induction of ISM resistance in a murine host. Administered ISM concentrations in immune-suppressed mice were gradually increased from 0.001 mg/kg to 1 mg/kg, the maximal dose used in livestock. As a result, three independent MSOROM7 lines acquired full resistance to this concentration after five months of induction, and retained this full resistant phenotype following a six months period without drug pressure. In contrast, parasites did not acquire ISM resistance in immune-competent animals, even after more than two years under ISM pressure, suggesting that the development of full ISM resistance is strongly enhanced when the host immune response is compromised. Genomic analyses comparing the ISM resistant lines with the parental sensitive line identified shifts in read depth at heterozygous loci in genes coding for different transporters and transmembrane products, and several of these shifts were also found within natural ISM resistant isolates. These findings suggested that the transport and accumulation of ISM inside the resistant parasites may be modified, which was confirmed by flow cytometry and ex vivo ISM uptake assays that showed a decrease in the accumulation of ISM in the resistant parasites.
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