ArticleInternational journal for parasitology. Drugs and drug resistance2014
A novel marker, ARM58, confers antimony resistance to Leishmania spp.
Article in International journal for parasitology. Drugs and drug resistance, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 29 citations in OpenAlex.
- Monoclonal antibodies: From magic bullet to precision weapon.Molecular biomedicine · 2024Review
- Unlocking the power of AI models: exploring protein folding prediction through comparative analysis.Journal of integrative bioinformatics · 2024Article
- Antimony resistance and gene expression inParasitology · 2024Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- High Content Analysis of Macrophage-TargetingMicroorganisms · 2021Article
- Monoclonal Antibodies for Protozoan Infections: A Future Reality or a Utopic Idea?Frontiers in medicine · 2021Review
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- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
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- Antimony resistance in Leishmania (Viannia) braziliensis clinical isolates from atypical lesions associates with increased ARM56/ARM58 transcripts and reduced drug uptake.Memorias do Instituto Oswaldo Cruz · 2019Article
- Molecular Preadaptation to Antimony Resistance in Leishmania donovani on the Indian Subcontinent.mSphere · 2018Article
- Selective human inhibitors of ATR and ATM render Leishmania major promastigotes sensitive to oxidative damage.PloS one · 2018Article
- Reverse Epidemiology: An Experimental Framework to DriveFrontiers in cellular and infection microbiology · 2018Review
- Biophysical and Pharmacological Characterization of Energy-Dependent Efflux of Sb in Laboratory-Selected Resistant Strains ofFrontiers in cell and developmental biology · 2017Article
- A Telomeric Cluster of Antimony Resistance Genes on Chromosome 34 of Leishmania infantum.Antimicrobial agents and chemotherapy · 2016Article
- Cos-Seq for high-throughput identification of drug target and resistance mechanisms in the protozoan parasite Leishmania.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The elements of life and medicines.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2015Article
- Intrachromosomal amplification, locus deletion and point mutation in the aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis.PLoS neglected tropical diseases · 2015Article
- Comparative Fitness of a Parent Leishmania donovani Clinical Isolate and Its Experimentally Derived Paromomycin-Resistant Strain.PloS one · 2015Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protozoa of the Leishmania genus cause a variety of disease forms that rank at the top of the list of neglected tropical diseases. Anti-leishmanial drugs based on pentavalent antimony have been the mainstay of therapy for over 60 years and resistance against them is increasingly encountered in the field. The biochemical basis for this is poorly understood and likely diverse. No stringent correlation between genetic markers and antimony resistance has so far been shown, prompting us to use a functional cloning approach to identify markers of resistance. Using gene libraries derived from drug-resistant and drug-sensitive Leishmania braziliensis clinical isolates in a functional cloning strategy, we repeatedly selected one gene locus located on chromosome 20 whose amplification confers increased antimony (III) resistance in vitro to an otherwise sensitive L. braziliensis clone. The gene responsible for the effect encodes a previously hypothetical protein that we dubbed LbrARM58. It comprises four repeats of a domain of unknown function, DUF1935, one of them harbouring a potential trans-membrane domain. The gene is so far unique to the Leishmania genus, while a structurally related gene without antimony resistance functionality is also found in Trypanosoma spp. Overexpression of LbrARM58 also confers antimony resistance to promastigotes and intracellular amastigotes of the related species Leishmania infantum, indicating a conserved function in Old World and New World Leishmania species. Our results also show that in spite of their RNAi system, L. braziliensis promastigotes can serve as acceptor cells for episomally propagated cosmid libraries, at least for the initial stages of functional cloning efforts.
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