Wang_2026_Pestic.Biochem.Physiol_218_106932

The sustained application of insecticides has led to the development of resistance. Carboxylesterases (CarEs) play important roles in the resistance and synergism of chlorantraniliprole and carbaryl. In this study, the key Spodoptera frugiperda CarEs gene, SfCarE, was identified. SfCarE was highly expressed at the 4th instar and in the midgut of the 6th instar larvae. Knockdown of SfCarE resulted in significant decrease in CarE activity and an increase in susceptibility to chlorantraniliprole, as well as to the mixture of chlorantraniliprole and carbaryl. Metabolic assays demonstrated that the SfCarE protein can metabolize both carbaryl and chlorantraniliprole, while carbaryl can effectively slow down the metabolism of chlorantraniliprole, thereby increasing its retention and insecticidal effect. Molecular docking and molecular dynamics simulation indicated that the predominant modes of interaction between SfCarE and the compounds were hydrogen bonds and van der Waals forces. Additionally, carbaryl exhibited a higher degree of stability in binding with SfCarE than chlorantraniliprole. Therefore, carbaryl was preferentially metabolized by SfCarE, which protecting chlorantraniliprole from metabolism. In summary, this study preliminarily reveals a synergistic mechanism in which the metabolic rate of chlorantraniliprole is reduced when combined with carbaryl. This research demonstrated that the SfCarE-mediated metabolic and synergistic interactions between chlorantraniliprole and carbaryl may provide valuable insights for the development of novel insecticidal combinations for integrated resistance management (IRM).