ArticleMolecular and biochemical parasitology2014
Benznidazole-resistance in Trypanosoma cruzi: evidence that distinct mechanisms can act in concert.
Article in Molecular and biochemical parasitology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 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
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- Synthesis and evaluation of nitroheterocyclic aromatic adamantane amides with trypanocidal activity. Part II.RSC medicinal chemistry · 2026Article
- A Single-Cell Methodology for Energy Metabolism Analysis in Parasitic Protozoa.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Transcriptomic and ultrastructural responses to Amiodarone-Itraconazole in naturally benznidazole-resistant and -susceptible Trypanosoma cruzi strains.PLoS neglected tropical diseases · 2026Article
- New insights for an old drug: difluoromethylornithine boosts the trypanocidal action of benznidazole onFrontiers in cellular and infection microbiology · 2026Article
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases.Tropical medicine and infectious disease · 2025Review
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- Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease.PLoS pathogens · 2024Review
- Advances in the Development of Carbonic Anhydrase Inhibitors as New Antiprotozoal Agents.Current medicinal chemistry · 2024Review
- Fifteen Years after the Definition ofLife (Basel, Switzerland) · 2023Review
- Repurposing of rabeprazole as an anti-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Benznidazole treatment leads to DNA damage in Trypanosoma cruzi and the persistence of rare widely dispersed non-replicative amastigotes in mice.PLoS pathogens · 2023Article
- Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?Biomolecules · 2023Review
- Genomic surveillance: a potential shortcut for effective Chagas disease management.Memorias do Instituto Oswaldo Cruz · 2023Article
- In silico investigation of cytochrome bc1 molecular inhibition mechanism against Trypanosoma cruzi.PLoS neglected tropical diseases · 2023Article
- Advances in the preclinical characterization of the antimicrobial peptide AS-48.Frontiers in microbiology · 2023Review
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Benznidazole is the main drug used to treat Trypanosoma cruzi infections. However, frequent instances of treatment failure have been reported. To better understand potential resistance mechanisms, we analysed three clones isolated from a single parasite population that had undergone benznidazole-selection. These clones exhibited differing levels of benznidazole-resistance (varying between 9 and 26-fold), and displayed cross-resistance to nifurtimox (2 to 4-fold). Each clone had acquired a stop-codon-generating mutation in the gene which encodes the nitroreductase (TcNTR) that is responsible for activating nitroheterocyclic pro-drugs. In addition, one clone had lost a copy of the chromosome containing TcNTR. However, these processes alone are insufficient to account for the extent and diversity of benznidazole-resistance. It is implicit from our results that additional mechanisms must also operate and that T. cruzi has an intrinsic ability to develop drug-resistance by independent sequential steps, even within a single population. This has important implications for drug development strategies.
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Registered trials
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