The green peach aphid, Myzus persicae, is a notorious pest worldwide. We collected a field population of the pest (FZQ-F) that exhibited high resistance to neonicotinoids. Exposure to neonicotinoids can induce oxidative damage in animals; however, it remains unclear whether antioxidant enzymes contribute to the innate immune response of neonicotinoid-resistant pests against high doses of insecticides. Treatment with sublethal doses of thiacloprid (LC10 and LC25) for 3, 6, 12, 24, 48, and 72 h resulted in significantly increased reactive oxygen species (ROS), including H2O2 content, in FZQ-F adults, indicating insecticide-induced oxidative stress. Additionally, the peroxidase activity in FZQ-F adults increased after thiacloprid exposure. Using comparative genomics, we identified 31 heme peroxidases in M. persicae with a typical “2Cys” structure, and phylogenetic analyses divided them into five groups. Comparative transcriptomes revealed that MpPxd2 and MpPxd4 were significantly upregulated in thiacloprid-treated aphids. Thiacloprid exposure significantly induced MpPxd2 and MpPxd4 expression levels, consistent with high H2O2 content and peroxidase activity. The knockdown of MpPxd2 or MpPxd4 in FZQ-F increased their susceptibility to imidacloprid, thiacloprid, and thiamethoxam, verifying the protective role of the heme peroxidases against neonicotinoids in aphids. The knockdown of MpPxd2 or MpPxd4 also led to shorter longevity and a low fecundity of adult aphids at 31 °C compared to controls. The results show that MpPxd2 or MpPxd4 is important in how cells respond to oxidative stress and may help resistant M. persicae pests to handle neonicotinoids.
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