INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Jiang Zhu,Ruinan Qu,Yawei Wang,Ruoyao Ni,Kai Tian,Chan Yang,Mei Li,Michael Kristensen,Xinghui Qiu
Populations of many insect species have evolved a variety of resistance mechanisms in response to insecticide selection. Current knowledge about mutations responsible for insecticide resistance is largely achieved from studies on target-site resistance, while much less is known about metabolic resistance. Although it is well known that P450 monooxygenases are one of the major players involved in insecticide metabolism and resistance, understanding mutation(s) responsible for CYP-mediated resistance has been a big challenge. In this study, we used the house fly to pursue a better understanding of P450 mediated insecticide resistance at the molecular level. Metabolism studies illustrated that CYP6G4 had a broad-spectrum metabolic activity in metabolizing insecticides. Population genotyping revealed that the CYP6G4v1 allele harboring a DNA insertion (MdIS1) had been selected in many house fly populations on different continents. Dual luciferase reporter assays identified that the MdIS1 contained a CncC/Maf binding site, and electrophoretic mobility shift assay confirmed that transcription factor CncC was involved in the MdIS1-mediated regulation. This study highlights the common involvement of the CncC pathway in adaptive evolution, and provides an interesting case supportive of parallel evolution in P450-mediated insecticide resistance in insects.
研究领域:
昆虫学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
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2019
·Vol. 75
·期 7
·2009-2019
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IF 3.255
Bo Hu,He Huang,Qi Wei,Miaomiao Ren,David K Mburu,Xiangrui Tian,Jianya Su
BACKGROUND Glutathione S -transferases (GSTs) are a superfamily of multifunctional dimeric proteins existing in both prokaryotic and eukaryotic organisms. They are involved in the detoxification of both endogenous and exogenous electrophiles, including insecticides. However, the molecular mechanisms underlying the regulation of GST genes in insects are poorly understood. RESULTS We first identified at least three GST genes involved in resistance to the insecticides chlorpyrifos and cypermethrin. Analysis of upstream sequences revealed that three GSTs ( SeGSTo2 , SeGSTe6 and SeGSTd3 ) harbor the same cap ‘n’ collar C/muscle aponeurosis fibromatosis (CncC/Maf) binding site, and SeGSTo2 and SeGSTe6 contain the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator (AhR/ARNT) binding site. Luciferase reporter assay showed co-transfection of reporter plasmid containing the SeGSTe6 promoter with CncC and/or Maf expressing constructs significantly boosted transcription. Similarly, AhR and/or ARNT expressing constructs also significantly increased the promoter activities. The co-transfection of mutated reporter plasmid with CncC/Maf or AhR/ARNT did not increase transcription activity anymore. Constitutive over-expression of CncC, Maf and AhR was also found in the HZ16 strain, which might be the molecular mechanism for up-regulated expression of multiple detoxification genes conferring resistance to insecticides. CONCLUSION These results suggest that CncC/Maf and AhR/ARNT coordinately regulate the expression of multiple GST genes involved in insecticide resistance in Spodoptera exigua . © 2019 Society of Chemical Industry
研究领域:
昆虫学
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分子生物学
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毒理学
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基因组学
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PubMed
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-13
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IF 5.1
Hu Bo,Deng Yuping,Lu Tao,Ren Miaomiao,Liu Kuitun,Rao Cong,Guo Hailiang,Su Jianya
Synthetic insecticides have been widely used for the prevention and control of disease vectors and agricultural pests. However, frequent uses of insecticides have resulted in the development of insecticide resistance in these insect pests. The resistance adversely affects the efficacy of insecticides, and seriously reduces the lifespan of insecticides. Therefore, resistance management requires new strategies to suppress insecticide resistance. Here, we confirm that CncC/Maf are the key regulators of various detoxification genes involved in insecticide resistance in Spodoptera exigua . Then, we develop a cell screening platform to identify the natural compound inhibitors of CncC/Maf and determine that sofalcone can act as a CncC/Maf inhibitor in vitro and in vivo. Bioassay results showed that sofalcone significantly enhanced the toxicity (more than 3-fold) of chlorpyrifos and lambda-cyhalothrin against S. exigua larvae. Finally, we demonstrate that sofalcone can greatly improve the susceptibility of S. exigua larvae to insecticides by inhibiting the activity of the ROS/CncC-dependent detoxifying enzymes and downregulating the expression levels of detoxification genes. CncC/Maf inhibitors can be used as broad-spectrum synergists to overcome insecticide resistance in pest populations. Altogether, our results demonstrate that reduced expression of detoxification genes resulting from suppression of transcriptional regulation of these genes contributes to controlling insecticide resistance, which provides a very novel and high-efficiency green resistance management strategy.
研究领域:
昆虫学
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分子生物学
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害虫管理
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PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2026
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IF 4.8
Chen Chen,Peng Shi,Haihua Wu,Tingting Zhang,Min Zhang,Xueyao Zhang
As key members of xenobiotic transcription factors (XFTs), CncC and Maf mediate insecticide sensitivity by regulating detoxification enzyme genes. In this study, with Locusta migratoria as a model, investigations revealed that LmCncC showed particularly high expression in the foregut, midgut, hindgut, and fat bodies. In contrast, LmMaf expression was predominantly localized to the midgut and fat bodies. Functional analysis demonstrated that RNAi-mediated knockdown of LmCncC / LmMaf significantly increased sensitivity to deltamethrin and imidacloprid. To identify the LmCncC - and LmMaf -regulated genes, a comparative transcriptomics analysis was constructed and further identified three key uridine diphosphate-glucuronosyltransferase (UGT) genes downstream of the CncC/Maf pathway. To investigate the role of UGTs in insecticide detoxification, treatment of L. migratoria with sulfinpyrazone, a UGT inhibitor, reduced UGT activity by 42.2% and enhanced sensitivity to imidacloprid and deltamethrin. Among these UGT genes, RNAi-mediated knockdown of LmUGT392C1 significantly enhanced susceptibility to imidacloprid in insecticide bioassays. CRISPR-Cas9-generated LmCncC and LmUGT392C1 mutants validated the essential role of this pathway in imidacloprid detoxification. To clarify the regulatory mechanism of the CncC/Maf signaling pathway on LmUGT392C1, a 2623 bp promoter sequence of LmUGT392C1 was obtained. Dual-luciferase reporter gene assays confirmed that co-overexpression of LmCncC and LmMaf directly activates the promoter of LmUGT392C1 . Our study elucidates the CncC/Maf- LmUGT392C1 regulatory axis in insecticide sensitivity, which is applicable to designing new formulations to overcome detoxification or identify potential new resistance mechanisms.
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高影响因子
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