ArticleParasitology research2013
P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance.
Article in Parasitology research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- In vitro susceptibility of Trypanosoma cruzi discrete typing units (DTUs) to benznidazole: A systematic review and meta-analysis.PLoS neglected tropical diseases · 2021Pooled it
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Discovery of pyrazole-based analogs as CDK2 inhibitors with apoptotic-inducing activity: design, synthesis and molecular dynamics study.RSC advances · 2024Article
- Role of Divalent Cations in Infections in Host-Pathogen Interaction.International journal of molecular sciences · 2024Review
- Bio-Guided Assay ofMolecules (Basel, Switzerland) · 2023Article
- Transcriptomic analysis of benznidazole-resistant and susceptible Trypanosoma cruzi populations.Parasites & vectors · 2023Article
- Genomic surveillance: a potential shortcut for effective Chagas disease management.Memorias do Instituto Oswaldo Cruz · 2023Article
- The History of the ABC Proteins in Human Trypanosomiasis Pathogens.Pathogens (Basel, Switzerland) · 2022Review
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.Frontiers in cellular and infection microbiology · 2022Article
- Promises and Pitfalls of Parasite Patch-clamp.Trends in parasitology · 2021Review
- Evaluation of the anti-Trypanosoma cruzi activity in vitro and in vivo of silibinin and silibinin in association to benznidazole.Parasitology research · 2021Article
- In vitro susceptibility to benznidazole, nifurtimox and posaconazole of Trypanosoma cruzi isolates from ParaguayBiomedica : revista del Instituto Nacional de Salud · 2020Article
- Review
- Amlodipine Increases the Therapeutic Potential of Ravuconazole upon Trypanosoma cruzi Infection.Antimicrobial agents and chemotherapy · 2020Article
- Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate.Parasites & vectors · 2019Article
- Drug transporter and oxidative stress gene expression in human macrophages infected with benznidazole-sensitive and naturally benznidazole-resistant Trypanosoma cruzi parasites treated with benznidazole.Parasites & vectors · 2019Article
- Functional Characterization of ABCC Proteins fromFrontiers in microbiology · 2018Article
- Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole.Scientific reports · 2017Article
- New Approaches to Overcome Transport Related Drug Resistance in Trypanosomatid Parasites.Frontiers in pharmacology · 2016Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance in protozoan parasites has been associated with the P-glycoprotein (Pgp), an energy-dependent efflux pump that transports substances across the membrane. Interestingly, the genes TcPGP1 and TcPGP2 have been described in Trypanosoma cruzi, although the function of these genes has not been fully elucidated. The main goal of this work was to investigate Pgp efflux pump activity and expression in T. cruzi lines submitted to in vitro induced resistance to the compounds 4-N-(2-methoxy styryl)-thiosemicarbazone (2-Meotio) and benznidazole (Bz) and to verify the stability of the resistant phenotypes during the parasite life cycle. We observed that the EC50 values for the treatment of epimastigotes with 2-Meotio or Bz were increased at least 4.7-fold in resistant lines, and this phenotype was maintained in metacyclic trypomastigotes, cell-derived trypomastigotes, and intracellular amastigotes. However, in epimastigotes, 2-Meotio resistance is reversible, but Bz resistance is irreversible. When compared with the parental line, the resistant lines exhibited higher Pgp efflux activity, reversion of the resistant phenotypes in the presence of Pgp inhibitors, cross-resistance with Pgp modulators, higher basal Pgp ATPase activity, and overexpression of the genes TcPGP1 and TcPGP2. In conclusion, the resistance induced in T. cruzi by the compounds 2-Meotio and Bz is maintained during the entire parasite life cycle. Furthermore, our data suggest the participation of the Pgp efflux pump in T. cruzi drug resistance.
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