ArticleAntimicrobial agents and chemotherapy2010
Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas' disease.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity.Memorias do Instituto Oswaldo Cruz · 2014Guideline
- Revisiting cysteine protease function inMicrobiology spectrum · 2026Article
- Induced pluripotent stem cell-derived human macrophages as an infection model for Trypanosoma cruzi.PLoS neglected tropical diseases · 2025Article
- Oral Pyronaridine Tetraphosphate Reduces Tissue Presence of Parasites in a Mouse Model of Chagas Disease.ACS omega · 2024Article
- Impact of Laboratory-Adapted IntracellularMicroorganisms · 2023Article
- State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation.Research and reports in tropical medicine · 2023Review
- Drug Repurposing in Chagas Disease: Chloroquine Potentiates Benznidazole Activity against Trypanosoma cruziAntimicrobial agents and chemotherapy · 2022Article
- Past and future of trypanosomatids high-throughput phenotypic screening.Memorias do Instituto Oswaldo Cruz · 2022Article
- The translational challenge in Chagas disease drug development.Memorias do Instituto Oswaldo Cruz · 2022Review
- Optimization and biological validation of anBiology methods & protocols · 2021Article
- Biospektrum : Zeitschrift der Gesellschaft fur Biologishe Chemie (GBCH) und der Vereinigung fur Allgemeine und Angewandte Mikrobiologie (VAAM) · 2021Review
- Repurposing Carvedilol as a Novel Inhibitor of theFrontiers in cellular and infection microbiology · 2021Article
- Non-invasive monitoring of drug action: A new live in vitro assay design for Chagas' disease drug discovery.PLoS neglected tropical diseases · 2020Article
- Of Drugs and Trypanosomatids: New Tools and Knowledge to Reduce Bottlenecks in Drug Discovery.Genes · 2020Review
- ImageJ for Partially and Fully Automated Analysis of Trypanosome Micrographs.Methods in molecular biology (Clifton, N.J.) · 2020Article
- In Vitro Image-Based Assay for Trypanosoma cruzi Intracellular Forms.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Drug Discovery for Chagas Disease: Impact of Different Host Cell Lines on Assay Performance and Hit Compound Selection.Tropical medicine and infectious disease · 2019Article
- Drug repurposing for antimicrobial discovery.Nature microbiology · 2019Review
- Innovation in neglected tropical disease drug discovery and development.Infectious diseases of poverty · 2018Review
- Identification of Anti-Trypanosoma cruzi Lead Compounds with Putative Immunomodulatory Activity.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Chagas' disease, caused by infection with the parasite Trypanosoma cruzi, is the major cause of heart failure in Latin America. Classic clinical manifestations result from the infection of heart muscle cells leading to progressive cardiomyopathy. To ameliorate disease, chemotherapy must eradicate the parasite. Current drugs are ineffective and toxic, and new therapy is a critical need. To expedite drug screening for this neglected disease, we have developed and validated a cell-based, high-throughput assay that can be used with a variety of untransfected T. cruzi isolates and host cells and that simultaneously measures efficacy against the intracellular amastigote stage and toxicity to host cells. T. cruzi-infected muscle cells were incubated in 96-well plates with test compounds. Assay plates were automatically imaged and analyzed based on size differences between the DAPI (4',6-diamidino-2-phenylindole)-stained host cell nuclei and parasite kinetoplasts. A reduction in the ratio of T. cruzi per host cell provided a quantitative measure of parasite growth inhibition, while a decrease in count of the host nuclei indicated compound toxicity. The assay was used to screen a library of clinically approved drugs and identified 55 compounds with activity against T. cruzi. The flexible assay design allows the use of various parasite strains, including clinical isolates with different biological characteristics (e.g., tissue tropism and drug sensitivity), and a broad range of host cells and may even be adapted to screen for inhibitors against other intracellular pathogens. This high-throughput assay will have an important impact in antiparasitic drug discovery.
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