An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes

Research output: Contribution to journalArticle

  • External authors:
  • Frederick A Partridge
  • Anwen E Brown
  • Steven D Buckingham
  • Nicky J Willis
  • Graham M Wynne
  • Alison A Morrison
  • Jacqueline B Matthews
  • Angela J Russell
  • David A Lomas
  • David B Sattelle

Abstract

Parasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and parasitic nematodes: Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, and Trichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified compounds already known to have anthelmintic or anti-parasitic activity, including tolfenpyrad, auranofin, and mebendazole; and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics.

Bibliographical metadata

Original languageEnglish
Pages (from-to)8-21
Number of pages14
JournalInternational journal for parasitology. Drugs and drug resistance
Volume8
Issue number1
Early online date2 Dec 2017
DOIs
Publication statusPublished - Apr 2018