Nrf2 Drives Deltamethrin Resistance of <i>Spodoptera frugiperda</i> by Directly Upregulating Multiple Detoxification Enzyme Genes

Chemical insecticides remain the most effective strategy for controlling agricultural pests; however, complex resistance in field pests has undermined pest management efforts. Identifying the key regulatory factors of resistance genes is crucial to effective resistance management. In this study, the expression mechanism of upregulated genes in deltamethrin-resistant <i>Spodoptera frugiperda</i> was studied. A total of 15 upregulated phase I and II detoxification enzymes were identified. RNAi of the antioxidative stress factor <i>Nrf2</i> significantly increased the sensitivity of the resistant larvae to deltamethrin by downregulating 13 genes, including the key cross-resistance gene <i>CYP321A8</i> previously demonstrated in field populations. The expression of these genes was directly promoted by Nrf2, as demonstrated by luciferase activity and binding assays, thereby enhancing the metabolic ability of <i>S. frugiperda</i> toward deltamethrin. Therefore, Nrf2 drives <i>S. frugiperda</i> resistance to deltamethrin by upregulating resistance genes, highlighting its potential as a target for resistance management in field <i>S. frugiperda</i>.