Cytochrome P450\nCYP6AE70 Confers Resistance to Multiple\nInsecticides in a Lepidopteran Pest, Spodoptera exigua

Cytochrome P450 monooxygenases are associated with the\ndetoxification\nof xenobiotics, and overexpression of P450 genes has been proven to\nbe associated with insecticide resistance in insect species. Our previous\nstudy has revealed that multiple CYP6AE genes were significantly overexpressed\nin a resistant strain of Spodoptera exigua, and among these genes, <i>CYP6AE70</i> was particularly\nhighly expressed. However, the functional roles of the <i>CYP6AE</i> genes in insecticide resistance remain unknown in this pest. Here,\nwe investigate the relationship between the CYP6AE genes and insecticide\nresistance by focusing on <i>CYP6AE70</i>. The expression\nof <i>CYP6AE70</i> was increased after exposure to chlorpyrifos,\ncypermethrin, and deltamethrin. Ectopic overexpression of P450 in\ntransgenic flies by the GAL4/UAS system dramatically enhanced the\ntolerance to these three insecticides. Furthermore, the recombinant\nCYP6AE70 was functionally expressed in Sf9 cells, and metabolic assays\nrevealed that the recombinant P450 protein could efficiently metabolize\nchlorpyrifos, cypermethrin, and deltamethrin. Finally, molecular modeling\nand docking also showed that this P450 protein were tightly bound\nto the three insecticides. These results determine that the upregulation\nof <i>CYP6AE genes</i> results in resistance to multiple\ninsecticides in S. exigua. This study\nimproves our understanding of P450-mediated insecticide resistance\nand will help us to design more effective resistance management for\npest control.