Development of a movement-based in vitro screening assay for the identification of new anti-cestodal compounds

PLoS Neglected Tropical Diseases
Dominic RitlerBritta Lundström-Stadelmann

Abstract

Intestinal cestodes are infecting millions of people and livestock worldwide, but treatment is mainly based on one drug: praziquantel. The identification of new anti-cestodal compounds is hampered by the lack of suitable screening assays. It is difficult, or even impossible, to evaluate drugs against adult cestodes in vitro due to the fact that these parasites cannot be cultured in microwell plates, and adult and larval stages in most cases represent different organisms in terms of size, morphology, and metabolic requirements. We here present an in vitro-drug screening assay based on Echinococcus multilocularis protoscoleces, which represent precursors of the scolex (hence the anterior part) of the adult tapeworm. This movement-based assay can serve as a model for an adult cestode screen. Protoscoleces are produced in large numbers in Mongolian gerbils and mice, their movement is measured and quantified by image analysis, and active compounds are directly assessed in terms of morphological effects. The use of the 384-well format minimizes the amount of parasites and compounds needed and allows rapid screening of a large number of chemicals. Standard drugs showed the expected dose-dependent effect on movement and morphology of t...Continue Reading

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Citations

Mar 14, 2020·Medicinal Research Reviews·Daniel Sepúlveda-CrespoMaría Martínez-Valladares
Apr 9, 2020·Frontiers in Cellular and Infection Microbiology·Congshan LiuHaobing Zhang
Jun 20, 2020·Beilstein Journal of Organic Chemistry·Frederick A PartridgeDavid B Sattelle
Feb 26, 2020·Food and Waterborne Parasitology·Britta Lundström-StadelmannAndrew Hemphill
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Abdelhalim B MahmoudPascal Mäser
Sep 23, 2021·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Mohaddeseh Abouhosseini TabariGiulia Bonacucina

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Methods Mentioned

BETA
FCS
motility assay
scanning electron microscopy

Software Mentioned

R
WormScan
NIS Elements
MolView
Parallel Worm Tracker
Adobe Illustrator
Worminator
Excel
JOBS
ImageJ

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