Overexpression of cytochrome P450 gene CYP402C18 contributes to the detoxification of dimpropyridaz, one novel pyridazine pyrazolecarboxamide insecticide, in the whitefly Bemisia tabaci Mediterranean cryptic species.

Bemisia tabaci is a major agricultural pest, and its widespread resistance to multiple insecticides poses a significant challenge for effective control. Dimpropyridaz, a new pyridazine-pyrazolecarboxamide insecticide, demonstrates high toxicity against sap-sucking pests, including those resistant to other class insecticides. However, the mechanisms underlying B. tabaci detoxification of dimpropyridaz remain unclear. In this study, transcriptome sequencing was performed on B. tabaci adults exposed to a lethal dose of dimpropyridaz for 48 h, identifying 973 differentially expressed genes (DEGs). GO and KEGG enrichment analyses revealed significant involvement of cytochrome P450 monooxygenases (P450s) in the detoxification pathway. Among the DEGs, a novel P450 gene, CYP402C18, was upregulated by 4.05-fold in response to dimpropyridaz and classified within the Clan3 CYP6 subfamily. Expression profiling revealed that CYP402C18 expression peaked in adults, with thoracic and head tissues exhibiting 5.18- and 1.64-fold higher levels, respectively, compared to the abdomen. Silencing CYP402C18 via dsRNA feeding significantly increased B. tabaci mortality to dimpropyridaz by 11.8 %. Molecular docking and dynamic simulations indicated stable binding between dimpropyridaz and CYP402C18, with a binding free energy of -35.89 kcal/mol. Notably, the alanine scanning results demonstrated that mutating the residues of Phe502 and Thr116 to alanine in CYP402C18 significantly reduced the binding energy with dimpropyridaz, indicating that these amino acids play a crucial role in the interaction with dimpropyridaz. These findings demonstrate that CYP402C18 contributes to dimpropyridaz detoxification and may be involved in resistance development, providing a theoretical basis for more targeted and sustainable use of dimpropyridaz in field management.