Discovery of Kaempferol, a Novel ADAM10 Inhibitor, as a Potential Treatment for Staphylococcus aureus Infection

文献类型： 外文期刊

第一作者： Wang, Tingting

作者： Wang, Tingting;Wang, Jianfeng;Deng, Xuming;Wang, Tingting;Wang, Jianfeng;Deng, Xuming;Wang, Tingting;Wang, Jianfeng;Xu, Xiangzhu;Jiang, Fan;Lv, Hongfa;Qi, Qinghui;Zhang, Can;Deng, Xuming;Wang, Tingting;Wang, Jianfeng;Xu, Xiangzhu;Jiang, Fan;Lv, Hongfa;Qi, Qinghui;Zhang, Can;Deng, Xuming;Wang, Jianfeng;Lv, Qianghua;Lv, Qianghua

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关键词： Host-directed therapy; Kaempferol; ADAM10 inhibitor; Staphylococcus aureus infection; Barrier disruption; Necroptosis

期刊名称：ENGINEERING （ 影响因子：12.8； 五年影响因子：13.6 ）

ISSN： 2095-8099

年卷期： 2023 年 28 卷

页码：

收录情况： SCI

摘要： Host-directed therapy (HDT) is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus (S. aureus) infection. Functioning as the indispensable specific cellular receptor for a-toxin (Hla), a-disintegrin and metalloproteinase 10 (ADAM10) is exploited to accelerate S. aureus infection through diverse mechanisms. The extraordinary contribution of ADAM10 to S. aureus pathogenesis renders it an attractive HDT target for combating S. aureus infection. Our study is the first to demonstrate the indispensable role of ADAM10 in S. aureus-induced necroptosis, and it enhances our knowledge of the role of ADAM10 in S. aureus infection. Using a fluorogenic substrate assay, we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S. aureus infection by suppressing Hla-mediated barrier disruption and necroptosis. Collectively, our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S. aureus infection and other diseases relevant to the disordered upregulation of ADAM10. (c) 2023 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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