Overexpression of Cytochrome P450 CYP12A2 Contributes to Pyridalyl Resistance in Plutella xylostella

Pyridalyl is a novel insecticide with a unique mode of action, but resistance in Plutella xylostella is a significant challenge. To elucidate the resistance mechanism, we compared transcriptomes of susceptible (XY-PS) and laboratory-selected resistant (XY-PR) strains. The mitochondrial cytochrome P450 gene CYP12A2 emerged as a key candidate. RT-qPCR confirmed CYP12A2 was upregulated approximately 8-fold in XY-PR and 9-fold in a field-collected resistant strain (ZL-PR). Furthermore, RNA interference (RNAi) targeting CYP12A2 significantly increased larval susceptibility to pyridalyl. Recombinant CYP12A2 expressed in Sf9 cells specifically metabolized pyridalyl, producing a distinct hydroxylated metabolite identified via UPLC-MS/MS. These findings represent direct evidence of P450-mediated metabolic detoxification of pyridalyl. Ultimately, this unveils a novel biochemical adaptation in P. xylostella, establishing CYP12A2 as a critical biomarker for field resistance monitoring and a promising target for integrated insecticide resistance management (IRM) strategies.