ArticlePloS one2013
Role of efflux pumps and intracellular thiols in natural antimony resistant isolates of Leishmania donovani.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Visceral leishmaniasis: an integrated review of resistance mechanisms, host immunometabolism, and next generation therapeutics.Inflammopharmacology · 2026Review
- Cutaneous and Mucocutaneous Leishmaniasis: Perspectives on Immunity, Virulence, and Treatment.Biomedicines · 2025Review
- Upregulation of antioxidant genes in antimony-resistant Leishmania tropica clinical isolates.Molecular biology reports · 2025Article
- Identification of CβS and ODC antimony resistance markers in anthroponotic cutaneous leishmaniasis field isolates by gene expression profiling.Parasite epidemiology and control · 2025Article
- Possibility of re-purposing antifungal drugs posaconazole & isavuconazole against promastigote form of Leishmania major.The Indian journal of medical research · 2024Article
- Antimony resistance and gene expression inParasitology · 2024Review
- Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host.Pathogens (Basel, Switzerland) · 2023Review
- Knockout of Tyrosine Aminotransferase Gene by Homologous Recombination Arrests Growth and Disrupts Redox Homeostasis in Leishmania Parasite.Parasitology research · 2022Article
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Simvastatin Resistance ofMicroorganisms · 2022Article
- Antileishmanial Drug Discovery and Development: Time to Reset the Model?Microorganisms · 2021Review
- Treatment failure to sodium stibogluconate in cutaneous leishmaniasis: A challenge to infection control and disease elimination.PloS one · 2021Article
- A Novel Bioimpedance-Based Detection of Miltefosine Susceptibility Among ClinicalFrontiers in cellular and infection microbiology · 2021Article
- Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance.Antimicrobial agents and chemotherapy · 2020Article
- Comparative mitochondrial proteomics of Leishmania tropica clinical isolates resistant and sensitive to meglumine antimoniate.Parasitology research · 2020Article
- Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil.Memorias do Instituto Oswaldo Cruz · 2018Article
- Biophysical and Pharmacological Characterization of Energy-Dependent Efflux of Sb in Laboratory-Selected Resistant Strains ofFrontiers in cell and developmental biology · 2017Article
- Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2016Article
- The LABCG2 Transporter from the Protozoan Parasite Leishmania Is Involved in Antimony Resistance.Antimicrobial agents and chemotherapy · 2016Article
- 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
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn view of the recent upsurge in the phenomenon of therapeutic failure, drug resistance in Leishmania, developed under natural field conditions, has become a great concern yet little understood. Accordingly, the study of determinants of antimony resistance is urgently warranted. Efflux transporters have been reported in Leishmania but their role in clinical resistance is still unknown. The present study was designed to elucidate the mechanism of natural antimony resistance in L. donovani field isolates by analyzing the functionality of efflux pump(s) and expression profiles of known genes involved in transport and thiol based redox metabolism. METHODOLOGY/PRINCIPAL
findingsWe selected 7 clinical isolates (2 sensitive and 5 resistant) in addition to laboratory sensitive reference and SbIII resistant mutant strains for the present study. Functional characterization using flow cytometry identified efflux pumps that transported substrates of both P-gp and MRPA and were inhibited by the calmodulin antagonist trifluoperazine. For the first time, verapamil sensitive efflux pumps for rhodamine 123 were observed in L. donovani that were differentially active in resistant isolates. RT-PCR confirmed the over-expression of MRPA in isolates with high resistance index only. Resistant isolates also exhibited consistent down regulation of AQP1 and elevated intracellular thiol levels which were accompanied with increased expression of ODC and TR genes. Interestingly, γ-GCS is not implicated in clinical resistance in L. donovani isolates. CONCLUSIONS/SIGNIFICANCE: Here we demonstrate for the first time, the role of P-gp type plasma membrane efflux transporter(s) in antimony resistance in L. donovani field isolates. Further, decreased levels of AQP1 and elevated thiols levels have emerged as biomarkers for clinical resistance.
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