ABSTRACT
Nematode parasites of humans, livestock and crops pose a significant burden on human health and welfare. Alarmingly, parasitic nematodes of animals have rapidly evolved resistance to anthelmintic drugs, and traditional nematicides that protect crops are facing increasing restrictions because of poor phylogenetic selectivity. Here, we present a pipeline that exploits multiple motor outputs of the model nematode C. elegans for nematicide discovery. This pipeline yielded a compound, which we call Nementin, that selectively immobilizes diverse nematode parasites. We find that Nementin induces convulsions by agonizing neuronal dense core vesicle release, which in turn agonizes cholinergic signaling. Consequently, Nementin synergistically enhances the potency of acetylcholinesterase inhibitors that are restricted agrochemicals. Nementin therefore represents a novel candidate nematicide that may improve the selectivity of broad-acting pesticides.
One-Sentence Summary A C. elegans-based screening pipeline identifies a selective nematicide that potentiates acetylcholinesterase inhibitors.
Competing Interest Statement
Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. USDA is an equal opportunity provider and employer. S.H., J.K., A.R.B., K-L.C., J.P., M.L. and P.J.R. have patents pending related to Nementin.
