ArticleAntimicrobial agents and chemotherapy2001
Alkyl-lysophospholipid resistance in multidrug-resistant Leishmania tropica and chemosensitization by a novel P-glycoprotein-like transporter modulator.
Article in Antimicrobial agents and chemotherapy, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 116 citations in OpenAlex.
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- In-Depth Quantitative Proteomics Characterization of In Vitro Selected Miltefosine Resistance inProteomes · 2022Article
- Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania.Nature communications · 2019Article
- A Leishmania infantum genetic marker associated with miltefosine treatment failure for visceral leishmaniasis.EBioMedicine · 2018Article
- Genomic and transcriptomic alterations in Leishmania donovani lines experimentally resistant to antileishmanial drugs.International journal for parasitology. Drugs and drug resistance · 2018Article
- Functional Characterization of ABCC Proteins fromFrontiers in microbiology · 2018Article
- Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.PLoS neglected tropical diseases · 2017Review
- Miltefosine Resistant Field Isolate From Indian Kala-Azar Patient Shows Similar Phenotype in Experimental Infection.Scientific reports · 2017Article
- Genomic Appraisal of the Multifactorial Basis for In Vitro Acquisition of Miltefosine Resistance in Leishmania donovani.Antimicrobial agents and chemotherapy · 2016Article
- Drug resistance in eukaryotic microorganisms.Nature microbiology · 2016Review
- Attenuation and Production of the Amphotericin B-Resistant Leishmania tropica Strain.Jundishapur journal of microbiology · 2016Article
- A New Antileishmanial Preparation of Combined Solamargine and Solasonine Heals Cutaneous Leishmaniasis through Different Immunochemical Pathways.Antimicrobial agents and chemotherapy · 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
- Case Report: No Response to Liposomal Daunorubicin in a Patient with Drug-Resistant HIV-Associated Visceral Leishmaniasis.PLoS neglected tropical diseases · 2015Article
- Antimony resistant Leishmania donovani but not sensitive ones drives greater frequency of potent T-regulatory cells upon interaction with human PBMCs: role of IL-10 and TGF-β in early immune response.PLoS neglected tropical diseases · 2014Article
- Antimony transport mechanisms in resistant leishmania parasites.Biophysical reviews · 2014Review
- A new ABC half-transporter in Leishmania major is involved in resistance to antimony.Antimicrobial agents and chemotherapy · 2013Article
- LABCG2, a new ABC transporter implicated in phosphatidylserine exposure, is involved in the infectivity and pathogenicity of Leishmania.PLoS neglected tropical diseases · 2013Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance has emerged as a major impediment in the treatment of leishmaniasis. Alkyl-lysophospholipids (ALP), originally developed as anticancer drugs, are considered to be the most promising antileishmanial agents. In order to anticipate probable clinical failure in the near future, we have investigated possible mechanisms of resistance to these drugs in Leishmania spp. The results presented here support the involvement of a member of the ATP-binding cassette (ABC) superfamily, the Leishmania P-glycoprotein-like transporter, in the resistance to ALP. (i) First, a multidrug resistance (MDR) Leishmania tropica line overexpressing a P-glycoprotein-like transporter displays significant cross-resistance to the ALP miltefosine and edelfosine, with resistant indices of 9.2- and 7.1-fold, respectively. (ii) Reduced expression of P-glycoprotein in the MDR line correlates with a significant decrease in ALP resistance. (iii) The ALP were able to modulate the P-glycoprotein-mediated resistance to daunomycin in the MDR line. (iv) We have found a new inhibitor of this transporter, the sesquiterpene C-3, that completely sensitizes MDR parasites to ALP. (v) Finally, the MDR line exhibits a lower accumulation than the wild-type line of bodipy-C(5)-PC, a fluorescent analogue of phosphatidylcholine that has a structure resembling that of edelfosine. Also, C-3 significantly increases the accumulation of the fluorescent analogue to levels similar to those of wild-type parasites. The involvement of the Leishmania P-glycoprotein-like transporter in resistance to drugs used in the treatment of leishmaniasis also supports the importance of developing new specific inhibitors of this ABC transporter.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.