ArticleAntimicrobial agents and chemotherapy2008
Inhibition of ABC transporters abolishes antimony resistance in Leishmania Infection.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 95 citations in OpenAlex.
- Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis.PLoS neglected tropical diseases · 2024Article
- Supramolecular assemblies from antimony(V) complexes for the treatment of leishmaniasis.Biophysical reviews · 2023Review
- Translational reprogramming as a driver of antimony-drug resistance in Leishmania.Nature communications · 2023Article
- Macrophage metallothioneins participate in the antileishmanial activity of antimonials.Frontiers in parasitology · 2023Article
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Transcriptomic Analysis in Human Macrophages Infected with Therapeutic Failure Clinical Isolates ofACS infectious diseases · 2022Article
- Metabolite Biomarkers ofCells · 2021Article
- Drug-Induced Lipid Remodeling inMicroorganisms · 2021Article
- Inductively coupled plasma mass spectrometry method for plasma and intracellular antimony quantification applied to pharmacokinetics of meglumine antimoniate.Bioanalysis · 2021Article
- A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among ClinicalFrontiers in cellular and infection microbiology · 2021Article
- Nucleic acid sensing activates the innate cytosolic surveillance pathway and promotes parasite survival in visceral leishmaniasis.Scientific reports · 2019Article
- 2'-Hydroxyflavanone activity in vitro and in vivo against wild-type and antimony-resistant Leishmania amazonensis.PLoS neglected tropical diseases · 2018Article
- Topical Treatment for Cutaneous Leishmaniasis: Dermato-Pharmacokinetic Lead Optimization of Benzoxaboroles.Antimicrobial agents and chemotherapy · 2018Article
- Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs.Clinical pharmacokinetics · 2018Review
- Functional Involvement of Leishmania donovani Tryparedoxin Peroxidases during Infection and Drug Treatment.Antimicrobial agents and chemotherapy · 2018Article
- Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility.Acta tropica · 2017Article
- Snapshot Profiling of the Antileishmanial Potency of Lead Compounds and Drug Candidates against Intracellular Leishmania donovani Amastigotes, with a Focus on Human-Derived Host Cells.Antimicrobial agents and chemotherapy · 2017Article
- Geographical Distribution of MDR1 Expression in Leishmania Isolates, from Greece and Cyprus, Measured by the Rhodamine-123 Efflux Potential of the Isolates, Using Flow Cytometry.The American journal of tropical medicine and hygiene · 2016Article
- Functional Validation of ABCA3 as a Miltefosine Transporter in Human Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA) PANAMENSIS.The Journal of biological chemistry · 2016Article
- New Approaches to Overcome Transport Related Drug Resistance in Trypanosomatid Parasites.Frontiers in pharmacology · 2016Review
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of antimony (Sb) resistance has jeopardized the treatment of visceral leishmaniasis in various countries. Previous studies have considered the part played by leishmanial parasites in antimony resistance, but the involvement of host factors in the clinical scenario remained to be investigated. Here we show that unlike infection with Sb-sensitive (Sbs) Leishmania donovani, infection with Sb-resistant (Sb r) L. donovani induces the upregulation of multidrug resistance-associated protein 1 (MRP1) and permeability glycoprotein (P-gp) in host cells, resulting in a nonaccumulation of intracellular Sb following treatment with sodium antimony gluconate (SAG) favoring parasite replication. The inhibition of MRP1 and P-gp with resistance-modifying agents such as lovastatin allows Sb accumulation and parasite killing within macrophages and offers protection in an animal model in which infection with Sb r L. donovani is otherwise lethal. The occurrence of a similar scenario in clinical cases is supported by the findings that unlike monocytes from SAG-sensitive kala-azar (KA) patients, monocytes from SAG-unresponsive KA patients overexpress P-gp and MRP1 and fail to accumulate Sb following in vitro SAG treatment unless pretreated with inhibitors of ABC transporters. Thus, the expression status of MRP1 and P-gp in blood monocytes may be used as a diagnostic marker for Sb resistance and the treatment strategy can be designed accordingly. Our results also indicate that lovastatin, which can inhibit both P-gp and MRP1, might be beneficial for reverting Sb resistance in leishmaniasis as well as drug resistance in other clinical situations, including cancer.
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