MAPK drives UGTs metabolic resistance to neonicotinoids in whitefly by regulating the transcription factor HR39Download PDF Download PDF ArticleOpen accessPublished: 19 September 2026Tianhua Du1,Hu Xue2,Lianyou Gui3,Jahangir Khajehali ORCID: orcid.org/0000-0002-3042-028X4,Xiaomao Zhou5,Xin Yang ORCID: orcid.org/0000-0001-8159-69232 &…Youjun Zhang ORCID: orcid.org/0000-0003-3508-66952 Communications Biology (2026) Cite this articleSave articleView saved research We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.AbstractMetabolic resistance is a critical and widespread mechanism enabling insects to develop resistance to diverse insecticides. However, the intricate pathways of metabolic detoxification and the underlying transcriptional regulatory mechanisms that drive insecticide resistance remain poorly understood. Here, we elucidate that elevated expression of Uridine diphosphate (UDP)-glycosyltransferases (UGTs) plays a pivotal role in enhancing detoxification metabolism in resistant Bemisia tabaci (whitefly). We successfully identify a key UGT gene BtUGT356B1, which directly metabolizes neonicotinoid insecticides such as thiamethoxam and imidacloprid. Through comprehensive in vitro and in vivo experiments, we discover that the P38/ERK kinases in the MAPK signaling pathway activate the transcription factor HR39 via phosphorylation, thereby promoting HR39 binding to the promoter region of the BtUGT356B1 to upregulate its transcription, and ultimately enhancing the detoxification ability of B. tabaci against neonicotinoids. This research not only clarifies the complex regulatory network of BtUGT356B1 mediated metabolic resistance but provides important theoretical foundations for a deeper understanding of insect resistance mechanisms.FundingThis research was financially supported by the National Natural Science Foundation of China (32221004, 32603829, 32361133558), China Agriculture Research System (CARS-24-C-02), Hainan Major Science and Technology Project (ZDKJ2021007), The Beijing Key Laboratory for Pest Control and Sustainable Cultivation of Vegetables and the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (CAAS-ASTIP-IVFCAAS), Beijing Natural Science Foundation (6212031), and Iranian National Science Foundation (INSF) (4001390).Author informationAuthors and AffiliationsCollege of Forestry, Central South University of Forestry and Technology, Changsha, P. R. ChinaTianhua DuState Key Laboratory of Vegetable Biobreeding, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, ChinaHu Xue, Xin Yang & Youjun ZhangHubei Engineering Technology Center for Pest Forewarning and Management, College of Agriculture, Yangtze University, Jingzhou, P. R. ChinaLianyou GuiDepartment of Plant Protection, College of Agriculture, Isfahan University of Technology, Isfahan, IranJahangir KhajehaliCollege of Plant Protection, Hunan Agricultural University, Changsha, P. R. ChinaXiaomao ZhouAuthorsTianhua DuView author publicationsSearch author on:PubMed Google ScholarHu XueView author publicationsSearch author on:PubMed Google ScholarLianyou GuiView author publicationsSearch author on:PubMed Google ScholarJahangir KhajehaliView author publicationsSearch author on:PubMed Google ScholarXiaomao ZhouView author publicationsSearch author on:PubMed Google ScholarXin YangView author publicationsSearch author on:PubMed Google ScholarYoujun ZhangView author publicationsSearch author on:PubMed Google ScholarCorresponding authorsCorrespondence to Xiaomao Zhou, Xin Yang or Youjun Zhang.Ethics declarationsCompeting interestsThe authors declare no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationRights and permissionsOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. 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