ArticleParasites & vectors2011
Gene expression study using real-time PCR identifies an NTR gene as a major marker of resistance to benzonidazole in Trypanosoma cruzi.
Article in Parasites & vectors, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- Interventions for Neglected Diseases Caused by Kinetoplastid Parasites: A One Health Approach to Drug Discovery, Development, and Deployment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- TrypPROTACs Unlocking New Therapeutic Strategies for Chagas Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Expression Analysis of Thirteen Genes in Response to Nifurtimox and Benznidazole in Mexican Isolates of Trypanosoma cruzi by Digital PCR.Acta parasitologica · 2025Article
- Transcriptomic analysis of benznidazole-resistant Trypanosoma cruzi clone reveals nitroreductase I-independent resistance mechanisms.PloS one · 2025Article
- Transcriptomic analysis of benznidazole-resistant and susceptible Trypanosoma cruzi populations.Parasites & vectors · 2023Article
- Molecular Characterization of Four Mexican Isolates of Trypanosoma cruzi and Their Profile Susceptibility to Nifurtimox.Acta parasitologica · 2022Article
- Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi.PLoS neglected tropical diseases · 2022Article
- Congenital transmission of Mexican strains ofParasitology · 2022Article
- Synthesis and biological evaluation in vitro and in silico of N-propionyl-N'-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi.Molecular diversity · 2022Article
- Intrinsic and Chemotherapeutic Stressors Modulate ABCC-Like Transport inMolecules (Basel, Switzerland) · 2021Article
- Correlation of NHR-48 Transcriptional Modulator Expression with Selected CYP Genes' Expression during Thiabendazole Treatment ofPathogens (Basel, Switzerland) · 2020Article
- In vitro susceptibility to benznidazole, nifurtimox and posaconazole of Trypanosoma cruzi isolates from ParaguayBiomedica : revista del Instituto Nacional de Salud · 2020Article
- Prostaglandin F2α synthase inRoyal Society open science · 2017Article
- Trypanosoma cruzi antioxidant enzymes as virulence factors in Chagas disease.Antioxidants & redox signaling · 2013Review
- P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance.Parasitology research · 2013Article
- Microsatellite and mini-exon analysis of Mexican human DTU I Trypanosoma cruzi strains and their susceptibility to nifurtimox and benznidazole.Vector borne and zoonotic diseases (Larchmont, N.Y.) · 2013Article
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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
backgroundChagas disease is a neglected illness, with limited treatments, caused by the parasite Trypanosoma cruzi. Two drugs are prescribed to treat the disease, nifurtimox and benznidazole, which have been previously reported to have limited efficacy and the appearance of resistance by T. cruzi. Acquisition of drug-resistant phenotypes is a complex physiological process based on single or multiple changes of the genes involved, probably in its mechanisms of action.
resultsThe differential genes expression of a sensitive Trypanosoma cruzi strain and its induced in vitro benznidazole-resistant phenotypes was studied. The stepwise increasing concentration of BZ in the parental strain generated five different resistant populations assessed by the IC(50) ranging from 10.49 to 93.7 μM. The resistant populations maintained their phenotype when the BZ was depleted from the culture for many passages. Additionally, the benznidazole-resistant phenotypes presented a cross-resistance to nifurtimox but not to G418 sulfate. On the other hand, four of the five phenotypes resistant to different concentrations of drugs had different expression levels for the 12 genes evaluated by real-time PCR. However, in the most resistant phenotype (TcR5x), the levels of mRNA from these 12 genes and seven more were similar to the parental strain but not for NTR and OYE genes, which were down-regulated and over-expressed, respectively. The number of copies for these two genes was evaluated for the parental strain and the TcR5x phenotype, revealing that the NTR gene had lost a copy in this last phenotype. No changes were found in the enzyme activity of CPR and SOD in the most resistant population. Finally, there was no variability of genetic profiles among all the parasite populations evaluated by performing low-stringency single-specific primer PCR (LSSP-PCR) and random amplified polymorphic DNA RAPD techniques, indicating that no clonal selection or drastic genetic changes had occurred for the exposure to BZ.
conclusionHere, we propose NTR as the major marker of the appearance of resistance to BZ.
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