Caenorhabditis elegans is a useful model for anthelmintic discovery

Andrew R. Burns, Genna M. Luciani, Gabriel Musso, Rachel Bagg, May Yeo, Yuqian Zhang, Luckshika Rajendran, John Glavin, Robert Hunter, Elizabeth Redman, Susan Stasiuk, Michael Schertzberg, G. Angus McQuibban, Conor R. Caffrey, Sean R. Cutler, Mike Tyers, Guri Giaever, Corey Nislow, Andy G. Fraser, Calum A. MacRae, John Gilleard and Peter J. Roy ()
Additional contact information
Andrew R. Burns: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Genna M. Luciani: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Gabriel Musso: Brigham and Women’s Hospital, Harvard Medical School, and Harvard Stem Cell Institute
Rachel Bagg: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
May Yeo: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Yuqian Zhang: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Luckshika Rajendran: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
John Glavin: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Robert Hunter: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Elizabeth Redman: Faculty of Veterinary Medicine, University of Calgary
Susan Stasiuk: Faculty of Veterinary Medicine, University of Calgary
Michael Schertzberg: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
G. Angus McQuibban: University of Toronto, 1 King's College Circle
Conor R. Caffrey: University of California
Sean R. Cutler: Center for Plant Cell Biology, University of California
Mike Tyers: Institute for Research in Immunology and Cancer, University of Montreal
Guri Giaever: University of British Columbia
Corey Nislow: University of British Columbia
Andy G. Fraser: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Calum A. MacRae: Brigham and Women’s Hospital, Harvard Medical School, and Harvard Stem Cell Institute
John Gilleard: Faculty of Veterinary Medicine, University of Calgary
Peter J. Roy: The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Parasitic nematodes infect one quarter of the world’s population and impact all humans through widespread infection of crops and livestock. Resistance to current anthelmintics has prompted the search for new drugs. Traditional screens that rely on parasitic worms are costly and labour intensive and target-based approaches have failed to yield novel anthelmintics. Here, we present our screen of 67,012 compounds to identify those that kill the non-parasitic nematode Caenorhabditis elegans. We then rescreen our hits in two parasitic nematode species and two vertebrate models (HEK293 cells and zebrafish), and identify 30 structurally distinct anthelmintic lead molecules. Genetic screens of 19 million C. elegans mutants reveal those nematicides for which the generation of resistance is and is not likely. We identify the target of one lead with nematode specificity and nanomolar potency as complex II of the electron transport chain. This work establishes C. elegans as an effective and cost-efficient model system for anthelmintic discovery.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8485

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DOI: 10.1038/ncomms8485

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