RRC ID 51361
Author Burns AR, Bagg R, Yeo M, Luciani GM, Schertzberg M, Fraser AG, Roy PJ.
Title The novel nematicide wact-86 interacts with aldicarb to kill nematodes.
Journal PLoS Negl Trop Dis
Abstract Parasitic nematodes negatively impact human and animal health worldwide. The market withdrawal of nematicidal agents due to unfavourable toxicities has limited the available treatment options. In principle, co-administering nematicides at lower doses along with molecules that potentiate their activity could mitigate adverse toxicities without compromising efficacy. Here, we screened for new small molecules that interact with aldicarb, which is a highly effective treatment for plant-parasitic nematodes whose toxicity hampers its utility. From our collection of 638 worm-bioactive compounds, we identified 20 molecules that interact positively with aldicarb to either kill or arrest the growth of the model nematode Caenorhabditis elegans. We investigated the mechanism of interaction between aldicarb and one of these novel nematicides called wact-86. We found that the carboxylesterase enzyme GES-1 hydrolyzes wact-86, and that the interaction is manifested by aldicarb's inhibition of wact-86's metabolism by GES-1. This work demonstrates the utility of C. elegans as a platform to search for new molecules that can positively interact with industrial nematicides, and provides proof-of-concept for prospective discovery efforts.
Volume 11(4)
Pages e0005502
Published 2017-4-1
DOI 10.1371/journal.pntd.0005502
PII PNTD-D-16-01935
PMID 28379972
PMC PMC5393889
MeSH Aldicarb / pharmacology* Amino Acid Sequence Animals Antinematodal Agents / chemistry Antinematodal Agents / pharmacology* Benzamides / pharmacology* Benzofurans / pharmacology* Caenorhabditis elegans / drug effects* Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics* Carboxylic Ester Hydrolases / antagonists & inhibitors Carboxylic Ester Hydrolases / genetics* Mutation Nematoda / drug effects* Sequence Alignment
IF 3.885
Times Cited 6
C.elegans tm4694