P450 gene CYP6a13 is responsible for cross‐resistance of insecticides in field populations of Spodoptera frugiperda.

Continuous and long‐term use of traditional and new pesticides can result in cross‐resistance among pest populations in different fields. Study on the mechanism of cross‐resistance and related genes will help resistance management and field pest control. In this study, the pesticide‐resistance mechanism in <italic>Spodoptera frugiperda</italic> (FAW) was studied with field populations in 3 locations of South China. Field FAW populations were highly resistant to traditional insecticides, chlorpyrifos (organophosphate) and deltamethrin (pyrethroid), and had higher levels of cytochrome P450 activity than a non‐resistant laboratory strain. Inhibition of P450 activity by piperonyl butoxide significantly increased the sensitivity of resistant FAW in 3 locations to chlorpyrifos, deltamethrin and chlorantraniliprole (amide), a new type of insecticide, suggesting that P450 detoxification is a critical factor for insecticide resistance in field FAW populations. Transcriptomic analysis indicated that 18 P450 genes were upregulated in the field FAW populations collected in 3 regions and in 2 consecutive years, with <italic>CYP6a13</italic>, the most significantly upregulated one. Knockdown of <italic>CYP6a13</italic> messenger RNA by RNA interference resulted in an increased sensitivity to the 3 tested insecticides in the field FAW. Enzyme activity and molecular docking analyses indicated that CYP6a13 enzyme was able to metabolize the 3 tested insecticides and interact with 8 other types of insecticides, confirming that <italic>CYP6a13</italic> is a key cross‐resistance gene with a wide range of substrates in the field FAW populations across the different regions and can be used as a biomarker and target for management of FAW insecticide resistance in fields. [ABSTRACT FROM AUTHOR]