Ravaynia, Paolo S. and Lombardo, Flavio C. and Biendl, Stefan and Dupuch, Matthias A. and Keiser, Jennifer and Hierlemann, Andreas and Modena, Mario M.. (2020) Parallelized impedance-based platform for continuous dose-response characterization of antischistosomal drugs. Advanced biosystems, 4 (7). e1900304.
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Official URL: https://edoc.unibas.ch/78488/
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Abstract
Schistosomiasis is an acute and chronic disease caused by tropical parasitic worms of the genus Schistosoma, which parasitizes annually over 200 million people worldwide. Screening of antischistosomal compounds is hampered by the low throughput and potential subjectivity of the visual evaluation of the parasite phenotypes, which affects the current drug assays. Here, an impedance-based platform, capable of assessing the viability of Schistosoma mansoni schistosomula exposed to drugs, is presented. This automated and parallelized platform enables unbiased and continuous measurements of dose-response relationships for more than 48 h. The platform performance is established by exposure of schistosomula to three test compounds, praziquantel, oxethazaine, and mefloquine, which are known to affect the larvae phenotypes. The system is thereafter used to investigate the response of schistosomula to methiothepine, an antipsychotic compound, which causes complex drug-induced effects. Continuous monitoring of the parasites reveals transient behavioral phenotypes and allows for extracting temporal characteristics of dose-response curves, which are essential for selecting drugs that feature high activity and fast kinetics of action. These measurements demonstrate that impedance-based detection provides a wealth of information for the in vitro characterization of candidate antischistosomals and, represents a promising tool for the identification of new lead compounds.
Faculties and Departments: | 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Helminth Drug Development (Keiser) |
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UniBasel Contributors: | Lombardo, Flavio and Biendl, Stefan and Keiser, Jennifer |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
ISSN: | 2366-7478 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Identification Number: |
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Last Modified: | 16 Dec 2022 11:39 |
Deposited On: | 16 Dec 2022 11:39 |
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