Identification of chemosensory protein inhibitors as a potential strategy to combat pyrethroid resistance in Anopheles gambiae

文献类型： 外文期刊

第一作者： Liu, Chen

作者： Liu, Chen;Sundarraj, Rajamanikandan;Yang, Ning;Yuchi, Zhiguang;Liu, Chen;Sundarraj, Rajamanikandan;Yang, Ning;Yuchi, Zhiguang;Liu, Chen;Sundarraj, Rajamanikandan;Yang, Ning;Yuchi, Zhiguang;Liu, Chen;Sundarraj, Rajamanikandan;Yang, Ning;Yuchi, Zhiguang;Liu, Chen;Sundarraj, Rajamanikandan;Yang, Ning;Yuchi, Zhiguang;Dong, Meijing;Yuchi, Zhiguang

作者机构：

关键词： chemosensory protein; resistance; Anopheles gambiae; cinnamaldehyde; synergist; insecticide

期刊名称：PEST MANAGEMENT SCIENCE （ 影响因子：3.8； 五年影响因子：4.3 ）

ISSN： 1526-498X

年卷期： 2025 年

页码：

收录情况： SCI

摘要： BACKGROUNDInsecticide resistance in Anopheles gambiae, the primary malaria vector, poses a serious threat to global public health. Chemosensory proteins (CSPs), key components of the insect olfactory system responsible for detecting chemical signals, have been implicated in insecticide resistance by binding and sequestering pyrethroids, thereby reducing their bioavailability at target sites. Developing effective strategies to counteract CSP-mediated insecticide resistance remains a critical challenge in modern vector and pest control.RESULTSIn this study, we identified two cinnamaldehyde derivatives, alpha-hexylcinnamaldehyde (HCA) and alpha-pentylcinnamaldehyde (PCA), as high-affinity ligands for Anopheles gambiae CSPs (AgCSPs). Isothermal titration calorimetry (ITC) assays revealed that HCA and PCA bind AgCSPs with significantly higher affinities than deltamethrin and permethrin. Notably, preincubation of AgCSPs with HCA and PCA effectively blocked pyrethroid binding, indicating competitive occupation of the same binding sites. Molecular docking and molecular dynamics (MD) simulations further elucidated the binding modes of these ligands, which were experimentally validated through site-directed mutagenesis. Bioassays with mosquito larvae confirmed the in vitro findings, showing that AgCSP-sequestered deltamethrin treatment significantly reduced larval mortality compared to deltamethrin alone. Importantly, the addition of PCA competitively displaced deltamethrin from AgCSPs, restoring its insecticidal efficacy.CONCLUSIONSOur findings suggest that high-affinity CSP inhibitors capable of competitively blocking insecticide sequestration represent a promising strategy for overcoming CSP-mediated resistance. This study provides a foundation for the development of novel insecticide synergists to enhance the efficacy of pyrethroids and combat resistance in malaria vectors. (c) 2025 Society of Chemical Industry.

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