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《工程(英文)》 >> 2023年 第28卷 第9期 doi: 10.1016/j.eng.2023.03.006

山奈酚作为新型ADAM10抑制剂治疗金黄色葡萄球菌感染

a Department of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases & Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Zoonotic Diseases, The First Hospital of Jilin University, Changchun 130021, China
b State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
c Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China
d Key Laboratory of Livestock and Poultry Multi-omics of MARA & Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, China

# These authors contributed equally to this work.

收稿日期: 2022-10-18 修回日期: 2023-02-19 录用日期: 2023-03-23 发布日期: 2023-04-14

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摘要

宿主靶向疗法(HDT)是近年来兴起一种的治疗多重耐药金黄色葡萄球菌(S. aureus,简称“金葡菌”)感染的新策略。去整合素和金属蛋白酶10(ADAM10)作为α-毒素(Hla)不可或缺的特异性细胞受体,可通过多种机制促进金葡菌感染。ADAM10在致病机制中发挥的关键作用使其成为基于HDT治疗金葡菌感染的有力靶点。本研究首次证明ADAM10在金葡菌诱导的坏死性调亡中也发挥重要作用,这一发现拓宽了人们对ADAM10在金葡菌感染中作用的认识。通过荧光底物分解试验,我们进一步筛选出了一种强效ADAM10抑制剂——山奈酚,该化合物可抑制Hla引起的屏障破坏和细胞坏死性调亡,有效保护小鼠免受金葡菌感染。总的来说,本研究提出了一种新的宿主靶向治疗策略,并提供了有较高应用前景的候选化合物山奈酚。

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