Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP

doi:10.1038/s41467-022-34753-0

	Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP
	Wei, Bingyan 1,2,3; Zhang, Tao 2; Wang, Pengyu 1,2,3; Pan, Yihui 1,2,3; Li, Jiahui 2,3; Chen, Weizhong4 ; Zhang, Min 5; Ji, Quanjiang4 ; Wu, Wenjuan 5; Lan, Lefu 1,2,3; Gan, Jianhua 6; Yang, Cai-Guang 1,2,3
	2022-11-14
发表期刊	NATURE COMMUNICATIONS
EISSN	2041-1723
卷号	13 期号:1
发表状态	已发表
DOI	10.1038/s41467-022-34753-0
摘要	The emergence of methicillin-resistant Staphylococcus aureus isolates highlights the urgent need to develop more antibiotics. ClpP is a highly conserved protease regulated by ATPases in bacteria and in mitochondria. Aberrant activation of bacterial ClpP is an alternative method of discovering antibiotics, while it remains difficult to develop selective Staphylococcus aureus ClpP activators that can avoid disturbing Homo sapiens ClpP functions. Here, we use a structure-based design to identify (R)- and (S)-ZG197 as highly selective Staphylococcus aureus ClpP activators. The key structural elements in Homo sapiens ClpP, particularly W146 and its joint action with the C-terminal motif, significantly contribute to the discrimination of the activators. Our selective activators display wide antibiotic properties towards an array of multidrug-resistant staphylococcal strains in vitro, and demonstrate promising antibiotic efficacy in zebrafish and murine skin infection models. Our findings indicate that the species-specific activators of Staphylococcus aureus ClpP are exciting therapeutic agents to treat staphylococcal infections.
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收录类别	SCIE ; SCI
语种	英语
资助项目	National Natural Science Foundation of China["22037007","81861138046","21725801","22107109"]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000883836600017
出版者	NATURE PORTFOLIO
Scopus 记录号	2-s2.0-85141846832
来源库	Scopus
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/251414
专题	物质科学与技术学院_PI研究组_季泉江组
通讯作者	Yang, Cai-Guang
作者单位	1.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China 2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Ctr Chem Biol, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China 5.Tongji Univ, Shanghai East Hosp, Dept Lab Med, Sch Med, Shanghai 200123, Peoples R China 6.Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China
推荐引用方式 GB/T 7714	Wei, Bingyan,Zhang, Tao,Wang, Pengyu,et al. Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP[J]. NATURE COMMUNICATIONS,2022,13(1).
APA	Wei, Bingyan.,Zhang, Tao.,Wang, Pengyu.,Pan, Yihui.,Li, Jiahui.,...&Yang, Cai-Guang.(2022).Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP.NATURE COMMUNICATIONS,13(1).
MLA	Wei, Bingyan,et al."Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP".NATURE COMMUNICATIONS 13.1(2022).