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.

Highlights

  • Management of insect pests predominately relies on synthetic chemical insecticides.Due to their widespread use, there has been a selective effect on insects, leading to the development of insecticide resistance

  • CYP9J32 showed the highest resistance to deltamethrin and cypermethrin in Thailand, Mexico, and Vietnam, CYP9J24 and CYP9J26 had the highest resistance to pyrethroids in Latin

  • Signalling pathway could reduce the expression of PKA and the resistant P450 genes after interference, resulting in an increase in the sensitivity of Cx. quinquefasciatus to permethrin, and revealing that the G protein-coupled receptors (GPCRs)/Gαs/AC/cAMP- PKA-mediated regulatory pathways control P450 gene expression in Cx. quinquefasciatus [135]. This regulatory pathway has been identified in field collected and laboratory-susceptible Cx. quinquefasciatus, indicating the general role of the GPCR regulatory cascade in the susceptibility of Cx. quinquefasciatus to insecticides, and its influence on the development of resistance through P450-mediated detoxification [136]. These results demonstrate the universal regulatory role of GPCR/Gαs/AC/PKA in insecticide resistance by showing that GPCR/Gαs/AC/PKA can regulate the expression of P450 genes related to insecticide resistance in insects such as Cx

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Summary

Introduction

Management of insect pests predominately relies on synthetic chemical insecticides. Due to their widespread use, there has been a selective effect on insects, leading to the development of insecticide resistance. Genes in members of these clans are involved in insect development, growth, and metabolism [4]. P450s are involved in the production of secondary metabolites that act as chemical defences, mitochondrial clans Many members of this enzyme family play important roles in while insect P450s metabolise the same to avoid toxicity. P450s provide a defensive role against xenobiotics, by participating in or interfering metabolites that act as chemical defences, while insect P450s metabolise the same with the specific activation of insecticide precursors, affecting insecticide selectivity [11]. Due to the development of molecular and bioinformatics reviews the characteristics and molecular mechanisms of P450s in mediating insecticide technologies, progress has been that made in the the identifying of ofP450 genes resistance, withsignificant a focus on the cascade reaction regulates expression. Sects and has been reported for many insecticides [12], such as pyrethroids [13], neoni-

P450-Mediated Insecticide Resistance
Cross Resistance
Evolutionary Adaptability
Molecular Mechanisms of P450-Mediated Insecticide Resistance
Upregulation of Enzyme Expression
Changes of Enzyme Functions
GPCRs Pathway
MAPK Pathway
PI3K Pathway
CncC Pathway
Nuclear Receptors
Management of P450-Mediated Insecticide Resistance
Findings
Summary and Prospects
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