ArticleAntimicrobial agents and chemotherapy2016
A Telomeric Cluster of Antimony Resistance Genes on Chromosome 34 of Leishmania infantum.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- 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
- 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
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania.Nature communications · 2019Article
- Genomewide Analysis of Mode of Action of themSystems · 2019Article
- 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
- High-throughput Cos-Seq screen with intracellular Leishmania infantum for the discovery of novel drug-resistance mechanisms.International journal for parasitology. Drugs and drug resistance · 2018Article
- Reverse Epidemiology: An Experimental Framework to DriveFrontiers in cellular and infection microbiology · 2018Review
- Extracellular Vesicle-Mediated Communication Within Host-Parasite Interactions.Frontiers in immunology · 2018Review
- Hsp90 inhibitors radicicol and geldanamycin have opposing effects on Leishmania Aha1-dependent proliferation.Cell stress & chaperones · 2017Article
- Biophysical and Pharmacological Characterization of Energy-Dependent Efflux of Sb in Laboratory-Selected Resistant Strains ofFrontiers in cell and developmental biology · 2017Article
- Plasticity of theF1000Research · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms underlying the drug resistance of Leishmania spp. are manifold and not completely identified. Apart from the highly conserved multidrug resistance gene family known from higher eukaryotes, Leishmania spp. also possess genus-specific resistance marker genes. One of them, ARM58, was first identified in Leishmania braziliensis using a functional cloning approach, and its domain structure was characterized in L. infantum Here we report that L. infantum ARM58 is part of a gene cluster at the telomeric end of chromosome 34 also comprising the neighboring genes ARM56 and HSP23. We show that overexpression of all three genes can confer antimony resistance to intracellular amastigotes. Upon overexpression in L. donovani, ARM58 and ARM56 are secreted via exosomes, suggesting a scavenger/secretion mechanism of action. Using a combination of functional cloning and next-generation sequencing, we found that the gene cluster was selected only under antimonyl tartrate challenge and weakly under Cu(2+) challenge but not under sodium arsenite, Cd(2+), or miltefosine challenge. The selective advantage is less pronounced in intracellular amastigotes treated with the sodium stibogluconate, possibly due to the known macrophage-stimulatory activity of this drug, against which these resistance markers may not be active. Our data point to the specificity of these three genes for antimony resistance.
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