山奈酚作为新型ADAM10抑制剂治疗金黄色葡萄球菌感染

Engineering ›› 2023, Vol. 28 ›› Issue (9) : 206 -221. DOI: 10.1016/j.eng.2023.03.006

研究论文

王婷婷 ^a^,^b ,
王建锋 ^a^,^b^,^c ,
许湘竹 ^b ,
蒋帆 ^b ,
吕红发 ^b ,
齐清辉 ^b ,
张灿 ^b ,
吕强华 ^d^,^* ,
邓旭明 ^a^,^b^,^*

作者信息 +

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

Tingting Wang ^a^,^b^,^# ,
Jianfeng Wang ^a^,^b^,^c^,^# ,
Xiangzhu Xu ^b ,
Fan Jiang ^b ,
Hongfa Lv ^b ,
Qinghui Qi ^b ,
Can Zhang ^b ,
Qianghua Lv ^d^,^* ,
Xuming Deng ^a^,^b^,^*

Author information +

文章历史 +

Received	Accepted	Published
2022-10-18	2023-03-23
Issue Date
2024-06-13

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Abstract

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 α-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 host-directed therapeutic strategy for using the promising candidate kaempferol to treat S. aureus infection and other diseases relevant to the disordered upregulation of ADAM10.