Knockdown of CYP9A9 increases the susceptibility to lufenuron, methoxyfenozide and a mixture of both in Spodoptera exigua

Lufenuron (LUF) and Methoxyfenozide (MET) as Insect Growth Regulators (IGRs) contribute to the current control of the catastrophic crop pest, Spodoptera exigua (Lepidoptera, Noctuidae). Yet S. exigua has evolved resistance to LUF and MET, which is possibly mediated by cytochrome P450 monooxygenases (P450s), particularly from the CYP3 clade family, as it plays a key role in the detoxification of insecticides. However, a mixture of LUF and MET (MML) (optimal ratio: 6:4) remains highly insecticidal. Here, we analysed the response of S. exigua to sublethal concentrations of LUF, MET, and MML via transcriptomics. Twelve differentially expressed genes (DEGs) encoding CYP3 clade members were observed in transcriptomes and CYP9A9 was significantly upregulated after treatment with LUF, MET, and MML. Further, CYP9A9 was most highly expressed in the midgut of L4 S. exigua larvae. RNAi-mediated knockdown of CYP9A9 reduced the activity of CYP450 and increased the susceptibility of S. exigua larvae to LUF, MET, and MML. Thus, CYP9A9 plays a key role in the detoxification of LUF, MET, and MML in S. exigua. These findings provide new insights into insecticidal actions of IGRs, which can be applied to the establishment of novel pest management strategies.