Enantioselective Neurotoxic Risk of Ethiprole Exposure to Honeybees: Prediction of Multidimensional Mechanisms

Abstract Limited research on the sublethal effects and mechanisms of chiral pesticides, particularly ethiprole, on honeybee neurobehavior at the enantiomeric level has obscured our understanding of the survival risks facing honeybees. We used transcriptomic sequencing, behavioral assay, correlation analysis, and molecular modeling to investigate the enantioselective neurotoxic risk of ethiprole on honeybees and predict potential molecular mechanisms. Our findings indicate that S-ethiprole poses a significant neurotoxicity hazard by markedly disrupting multiple signaling pathways and altering the expression of more genes, primarily by targeting the Rho subfamily of the small GTPase superfamily. This disruption likely accounts for the impairment of the gustatory response behavior in honeybees. Furthermore, Rac protein emerges as a potential molecular target through which S-ethiprole influences signal transduction in honeybees, correlating with decreased Snodgrassella abundance and the accumulation of N-benzoyl-N′-(2-chlorophenyl)thiourea induced by S-ethiprole. These results contribute to understanding the enantioselective neurotoxic risks and mechanisms of chiral ethiprole on honeybees.