ArticleThe Journal of infectious diseases2012
Benznidazole-resistance in Trypanosoma cruzi is a readily acquired trait that can arise independently in a single population.
Article in The Journal of infectious diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- In vitro susceptibility of Trypanosoma cruzi discrete typing units (DTUs) to benznidazole: A systematic review and meta-analysis.PLoS neglected tropical diseases · 2021Pooled it
- Glycocalyx-Driven Immunomodulation in Trypanosoma cruzi: Structures, Host Responses, Diagnostic and Therapeutic Targeting.Parasite immunology · 2026Review
- Multitarget Therapeutic Strategies for Chagas Disease: Natural Compounds, Antimicrobial Peptides, and Cell-Based Immunomodulation.Infectious disease reports · 2026Review
- ExploringAntimicrobial agents and chemotherapy · 2026Article
- A Single-Cell Methodology for Energy Metabolism Analysis in Parasitic Protozoa.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Trypanosomatid parasites, translational research in a One Health, One World environment.Frontiers in chemistry · 2026Review
- Synthesis and In Vitro Activity of Hypofuran B and Analogs Against Plasmodium Falciparum and Trypanosoma Cruzi.ChemMedChem · 2026Article
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Cytosporone B Affects ATP Production ofACS omega · 2025Article
- Intermittent suppressive posaconazole therapy is ineffective at mitigating cardiac and digestive tract pathologies in an experimental model of chronic Chagas disease.Antimicrobial agents and chemotherapy · 2025Article
- Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases.Tropical medicine and infectious disease · 2025Review
- Efficient constitution of a library of rotenoid analogs active againstRSC advances · 2025Article
- Repositioning FDA-Approved Sulfonamide-Based Drugs as Potential Carbonic Anhydrase Inhibitors inPharmaceuticals (Basel, Switzerland) · 2025Article
- 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
- A Computational Approach Using α-Carbonic Anhydrase to Find Anti-Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- Transcriptomic analysis of benznidazole-resistant Trypanosoma cruzi clone reveals nitroreductase I-independent resistance mechanisms.PloS one · 2025Article
- PUF3 RNA binding protein ofHeliyon · 2024Article
- A panel of phenotypically and genotypically diverse bioluminescent:fluorescent Trypanosoma cruzi strains as a resource for Chagas disease research.PLoS neglected tropical diseases · 2024Article
- Hybrid-Capture Target Enrichment in Human Pathogens: Identification, Evolution, Biosurveillance, and Genomic Epidemiology.Pathogens (Basel, Switzerland) · 2024Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Benznidazole is the frontline drug used against Trypanosoma cruzi, the causative agent of Chagas disease. However, treatment failures are often reported. Here, we demonstrate that independently acquired mutations in the gene encoding a mitochondrial nitroreductase (TcNTR) can give rise to distinct drug-resistant clones within a single population. Following selection of benznidazole-resistant parasites, all clones examined had lost one of the chromosomes containing the TcNTR gene. Sequence analysis of the remaining TcNTR allele revealed 3 distinct mutant genes in different resistant clones. Expression studies showed that these mutant proteins were unable to activate benznidazole. This correlated with loss of flavin mononucleotide binding. The drug-resistant phenotype could be reversed by transfection with wild-type TcNTR. These results identify TcNTR as a central player in acquired resistance to benznidazole. They also demonstrate that T. cruzi has a propensity to undergo genetic changes that can lead to drug resistance, a finding that has implications for future therapeutic strategies.
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Registered trials
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.