The Role of Insect Cytochrome P450s in Mediating Insecticide Resistance

Abstract

In many organisms, cytochrome P450 enzymes are the primary detoxifying enzymes. Enhanced P450 activity can be mediated by the emergence of new genes, increased transcription due to mutations in the promoter regions, changes in enzyme structures and functions due to mutations in protein-coding regions, or changes in post-translational modifications; all of these changes are subject to insecticide selection pressure. Multiple signalling pathways and key effector molecules are involved in the regulation of insect P450s. Increased P450 activity is a key mechanism inducing insect resistance. Hence, downregulation of selected P450s is a promising strategy to overcome this resistance. Insect P450 inhibitors that act as insecticide synergists, RNA interference to induce P450 gene silencing, and the use of transgenic insects and crops are examples of strategies utilized to overcome resistance. This article reviews the latest advances in studies related to insect P450s-mediated agrochemical resistance, with focuses on the regulatory mechanisms and associated pest management strategies. Future investigations on the comprehensive regulatory pathways of P450-mediated detoxification, identification of key effectors, and downregulation strategies for P450s will ecologically, economically, and practically improve pest management.

The insecticidal effect of the botanical insecticide chlorogenic acid on Mythimna separata (Walker) is related to changes in MsCYP450 gene expression

“…CYP450 genes play a significant role in detoxification in insects, and insecticide resistance largely depends on the metabolism of exogenous toxic substances by CYP450s (Nauen et al, 2021;Lu et al, 2020). Increased P450 activity is a key mechanism inducing insect resistance (Ye et al, 2022). Wang et al demonstrated that AmCYP9q1 plays an important role in the metabolic detoxification of imidacloprid by Apis mellifera larvae .…”

Detection of chlorfenapyr resistance in the malaria vector Anopheles gambiae contrasts with full susceptibility in Anopheles funestus across Africa

“…Metabolic detoxi cation is very common in mosquitoes and considered to be more likely to cause control failure 9 . The rst phase of metabolic resistance involves the cytochrome P450 (CYP) enzyme system and other detoxifying metabolic enzymes that catalyse the oxidation reaction of insecticides; the second stage involves uridine diphosphate (UDP) glucosyltransferases (UGTs), which form various conjugated metabolites through conjugation; nally, in the third phase, the ATP-binding cassette transporters (ABC transporters) are involved in eliminating the second-stage metabolites from cells 10 . In An funestus, metabolic resistance to pyrethroids is mainly driven by CYP6s and CYP9s genes family such as CYP6P9a, CYP6P9b, CYP6K1, CYP4M7, CYP325A, CYP9J11, CYP9K1, CYP6P5, CYP6P4a/b and GSTs such as GSTe2 [11][12][13][14] .…”

Detection of a reduced susceptibility to chlorfenapyr in the malaria vector Anopheles gambiae contrasts with full susceptibility in Anopheles funestus across Africa

“…Compared to target-site resistance, metabolic detoxification is very common in mosquitoes and considered to be more likely to cause control failure 9 . The first phase of metabolic resistance involves the cytochrome P450 (CYP) enzyme system and other detoxifying metabolic enzymes that catalyse the oxidation reaction of insecticides; the second stage involves uridine diphosphate (UDP) glucosyltransferases (UGTs), which form various conjugated metabolites through conjugation; finally, in the third phase, the ATP-binding cassette transporters (ABC transporters) are involved in eliminating the second-stage metabolites from the cells 10 . In An.…”