PT  - JOURNAL ARTICLE
AU  - Sean Harrington
AU  - Jessica J. Knox
AU  - Andrew R. Burns
AU  - Ken-Loon Choo
AU  - Aaron Au
AU  - Megan Kitner
AU  - Cecile Haeberli
AU  - Jacob Pyche
AU  - Cassandra D’Amata
AU  - Yong- Hyun Kim
AU  - Jonathan R. Volpatti
AU  - Maximillano Guiliani
AU  - Jamie Snider
AU  - Victoria Wong
AU  - Bruna M. Palmeira
AU  - Elizabeth M. Redman
AU  - Aditya S. Vaidya
AU  - John Gilleard
AU  - Igor Stagljar
AU  - Sean R. Cutler
AU  - Daniel Kulke
AU  - James J. Dowling
AU  - Christopher M. Yip
AU  - Jennifer Keiser
AU  - Inga Zasada
AU  - Mark Lautens
AU  - Peter J. Roy
TI  - A Nematode-Selective Potentiator of Organophosphate and Carbamate Agrochemicals
AID  - 10.1101/2022.03.12.484074
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.12.484074
4099  - http://biorxiv.org/content/early/2022/03/14/2022.03.12.484074.short
4100  - http://biorxiv.org/content/early/2022/03/14/2022.03.12.484074.full
AB  - 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 StatementMention 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.