Dysregulation of ClpP by Small-Molecule Activators Used Against Xanthomonas oryzae pv. oryzae Infections

doi:10.1021/acs.jafc.1c01470

	Dysregulation of ClpP by Small-Molecule Activators Used Against Xanthomonas oryzae pv. oryzae Infections
	Yang, Teng 1,2; Zhang, Tao 2; Zhou, Xiang 1; Wang, Pengyu 2,3; Gan, Jianhua 4; Song, Baoan 1; Yang, Song 1; Yang, Cai-Guang 2,3,5
刊名	JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
	2021-07-14
卷号	69 期号:27 页码:7545-7553
关键词	rice bacterial leaf blight caseinolytic protease P (ClpP) filamentous temperature-sensitive Z (FtsZ) ONC212 ADEP4 activator anti-Xoo infection
ISSN号	0021-8561
DOI	10.1021/acs.jafc.1c01470
通讯作者	Yang, Song(jhzx.msm@gmail.com) ; Yang, Cai-Guang(yangcg@simm.ac.cn)
英文摘要	Rice bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is considered a destructive plant bacterial disease. The looming crisis of antibiotic resistance necessitates the discovery of antibiotics with new modes of action. Activated caseinolytic protease P (ClpP) can degrade bacterial FtsZ proteins that are essential for cell division; thus, we hypothesized that small-molecule-induced dysregulation of XooClpP may result in degradation of XooFtsZ to treat leaf blight diseases. In this work, we have determined the crystal structures of XooClpP, and its mutant bound with ADEP4, which revealed the action modes of XooClpP assemblies and XooFtsZ degradation by dysregulated XooClpP in the presence of small-molecule activators, such as ONC212 and ADEP4. Additionally, an antibacterial assessment demonstrated that ONC212 displays excellent activity against Xoo and prevents rice bacterial leaf blight in vivo. Thus, these unique antibacterial effects of small-molecule activators of XooClpP represent a potential strategy for the development of agricultural antibiotics by targeting bacterial ClpP.
资助项目	National Natural Science Foundation of China[22037007] ; National Natural Science Foundation of China[21877021] ; National Natural Science Foundation of China[21725801]
WOS关键词	STAPHYLOCOCCUS-AUREUS ; PROTEASE ; FTSZ ; RESISTANCE ; VIRULENCE ; BACTERIA ; POTENT
WOS研究方向	Agriculture ; Chemistry ; Food Science & Technology
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000674324600003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296756]
专题	中国科学院上海药物研究所
通讯作者	Yang, Song; Yang, Cai-Guang
作者单位	1.Guizhou Univ, Ctr R&D Fine Chem, State Key Lab Breeding Base Green Pesticide & Agr, Key Lab Green Pesticide & Agr Bioengn,Minist Educ, Guiyang 550025, Peoples R China 2.Chinese Acad Sci, Ctr Chem Biol, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China 5.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
推荐引用方式 GB/T 7714	Yang, Teng,Zhang, Tao,Zhou, Xiang,et al. Dysregulation of ClpP by Small-Molecule Activators Used Against Xanthomonas oryzae pv. oryzae Infections[J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2021,69(27):7545-7553.
APA	Yang, Teng.,Zhang, Tao.,Zhou, Xiang.,Wang, Pengyu.,Gan, Jianhua.,...&Yang, Cai-Guang.(2021).Dysregulation of ClpP by Small-Molecule Activators Used Against Xanthomonas oryzae pv. oryzae Infections.JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,69(27),7545-7553.
MLA	Yang, Teng,et al."Dysregulation of ClpP by Small-Molecule Activators Used Against Xanthomonas oryzae pv. oryzae Infections".JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 69.27(2021):7545-7553.