PUBLICATION
Caenorhabditis elegans is a useful model for anthelmintic discovery
- Authors
- Burns, A.R., Luciani, G.M., Musso, G., Bagg, R., Yeo, M., Zhang, Y., Rajendran, L., Glavin, J., Hunter, R., Redman, E., Stasiuk, S., Schertzberg, M., Angus McQuibban, G., Caffrey, C.R., Cutler, S.R., Tyers, M., Giaever, G., Nislow, C., Fraser, A.G., MacRae, C.A., Gilleard, J., Roy, P.J.
- ID
- ZDB-PUB-150626-12
- Date
- 2015
- Source
- Nature communications 6: 7485 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Anthelmintics/chemistry
- Anthelmintics/pharmacology*
- Caenorhabditis elegans/drug effects*
- Caenorhabditis elegans/genetics
- Caenorhabditis elegans Proteins/genetics
- Caenorhabditis elegans Proteins/metabolism
- Drug Resistance/genetics
- Electron Transport Complex II/antagonists & inhibitors
- Electron Transport Complex II/metabolism
- HEK293 Cells
- Humans
- Models, Molecular
- Molecular Structure
- Phylogeny
- Protein Conformation
- Species Specificity
- Structure-Activity Relationship
- Zebrafish
- PubMed
- 26108372 Full text @ Nat. Commun.
Citation
Burns, A.R., Luciani, G.M., Musso, G., Bagg, R., Yeo, M., Zhang, Y., Rajendran, L., Glavin, J., Hunter, R., Redman, E., Stasiuk, S., Schertzberg, M., Angus McQuibban, G., Caffrey, C.R., Cutler, S.R., Tyers, M., Giaever, G., Nislow, C., Fraser, A.G., MacRae, C.A., Gilleard, J., Roy, P.J. (2015) Caenorhabditis elegans is a useful model for anthelmintic discovery. Nature communications. 6:7485.
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.
Errata / Notes
This article is corrected by ZDB-PUB-220906-210 .
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping