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Inhibitory Effect of Fluralaner on GABA Receptor Subunit RDL of Bactrocera dorsalis

Xiangyi Zhou,Guoxing Chen,Keying Chen,Zhanyi Xu,Jiali Qian,Ru Yan,Bosheng Chen,Huiming Wu,Mengli Chen

Simple SummaryBactrocera dorsalis(Hendel) (Diptera: Tephritidae), a highly invasive pest with high transmissibility and adaptability, causes severe damage to various commercial vegetables and fruits. RDL, as the homomeric subunit of γ-aminobutyric acid (GABA) receptors, is the target of several insecticides. In this study, we found thatBdRdlwas highly expressed in the pupae and heads of male and female adult insects. Also, BdRDL was functionally characterized inXenopus oocytesby two-electrode voltage clamping and we found that fluralaner worked as an antagonist of BdRDL. Furthermore, we found that fluralaner exhibited a comparable insecticidal activity to avermectin againstB. dorsalisadults. Finally, the modeling and molecular docking predicted that fluralaner interacted with BdRDL via hydrogen bonds. These results suggested that fluralaner, as an antagonist of BdRDL, could be used to controlB. dorsalis.Bactrocera dorsalis(Hendel) (Diptera: Tephritidae), a highly destructive pest, affects fruits and vegetables globally, leading to significant economic losses. As a homomeric subunit of γ-aminobutyric acid (GABA) receptors, RDL plays a crucial role in various physiological activities in insects. However, functional characterization of RDL fromB. dorsalishas not yet been elucidated. Here, we cloned theRdlgene fromB. dorsalis,BdRdl, and investigated the expression pattern ofBdRdl. The results showed thatBdRdlwas highly expressed in pupae and the heads of male and female adults. Also, we characterized the BdRDL inXenopus oocytesthrough two-electrode voltage clamping. It turned out that the inward current of BdRDL induced by GABA was followed in a dose-dependent manner with a median effective concentration (EC50) of 2.4 × 10−4M. Additionally, we determined the mode action of fluralaner, a new insecticide, on BdRDL in oocytes. We found that fluralaner significantly inhibited the currents induced by GABA, suggesting that fluralaner worked as an antagonist of BdRDL. Furthermore, we found that fluralaner exhibited a comparable insecticidal activity to avermectin againstB. dorsalisadults. Lastly, the modeling and molecular docking predicted that fluralaner interacted with RDL via hydrogen bonds. Our results not only characterized the RDL ofB. dorsalis, but also revealed that fluralaner works as an antagonist of BdRDL and could be used as an effective strategy forB. dorsaliscontrol.