Changes in both trans- and cis-regulatory elements mediate insecticide resistance in a lepidopteron pest, Spodoptera exigua

The evolution of insect resistance to insecticides is frequently associated with overexpression of one or more cytochrome P450 enzyme genes. Although overexpression of CYP450 genes is a well-known mechanism of insecticide resistance, the underlying regulatory mechanisms are poorly understood. Here w...

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Bibliographic Details
Published in:PLoS genetics 2021-03, Vol.17 (3), p.e1009403
Main Authors: Hu, Bo, Huang, He, Hu, Songzhu, Ren, Miaomiao, Wei, Qi, Tian, Xiangrui, Esmail Abdalla Elzaki, Mohammed, Bass, Chris, Su, Jianya, Reddy Palli, Subba
Format: Article
Language:English
Subjects:
Binding sites
Bioassays
Biology and Life Sciences
Cytochrome
DNA
Enzymatic activity
Enzymes
Gene regulation
Genes
Genetic aspects
Insecticide resistance
Insecticides
Insects
Lepidoptera
Metabolism
Molecular modelling
Mortality
Mutation
Natural history
Pesticide resistance
Physiological aspects
Proteins
Regulatory sequences
Research and Analysis Methods
Transcription factors
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Summary:The evolution of insect resistance to insecticides is frequently associated with overexpression of one or more cytochrome P450 enzyme genes. Although overexpression of CYP450 genes is a well-known mechanism of insecticide resistance, the underlying regulatory mechanisms are poorly understood. Here we uncovered the mechanisms of overexpression of the P450 gene, CYP321A8 in a major pest insect, Spodoptera exigua that is resistant to multiple insecticides. CYP321A8 confers resistance to organophosphate (chlorpyrifos) and pyrethroid (cypermethrin and deltamethrin) insecticides in this insect. Constitutive upregulation of transcription factors CncC/Maf are partially responsible for upregulated expression of CYP321A8 in the resistant strain. Reporter gene assays and site-directed mutagenesis analyses demonstrated that CncC/Maf enhanced the expression of CYP321A8 by binding to specific sites in the promoter. Additional cis-regulatory elements resulting from a mutation in the CYP321A8 promoter in the resistant strain facilitates the binding of the orphan nuclear receptor, Knirps, and enhances the promoter activity. These results demonstrate that two independent mechanisms; overexpression of transcription factors and mutations in the promoter region resulting in a new cis-regulatory element that facilitates binding of the orphan nuclear receptor are involved in overexpression of CYP321A8 in insecticide-resistant S. exigua.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1009403