Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence

doi:10.1038/NCHEMBIO.2003

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence
	Chen, Feifei 2; Di, Hongxia 2; Wang, Youxin 3; Cao, Qiao 2; Xu, Bin2 ; Zhang, Xue 2; Yang, Nana 2; Liu, Guijie 2; Yang, Cai-Guang2 ; Xu, Yong 4
刊名	NATURE CHEMICAL BIOLOGY
	2016-03
卷号	12 期号:3 页码:174-179
ISSN号	1552-4450
DOI	10.1038/NCHEMBIO.2003
文献子类	Article
英文摘要	The surge of antibiotic resistance in Staphylococcus aureus has created a dire need for innovative anti-infective agents that attack new targets, to overcome resistance. In S. aureus, carotenoid pigment is an important virulence factor because it shields the bacterium from host oxidant killing. Here we show that naftifine, a US Food and Drug Administration (FDA)-approved anti fungal drug, blocks biosynthesis of carotenoid pigment at nanomolar concentrations. This effect is mediated by competitive inhibition of S. aureus diapophytoene desaturase (CrtN), an essential enzyme for carotenoid pigment synthesis. We found that naftifine attenuated the virulence of a variety of clinical S. aureus isolates, including methicillin-resistant S. aureus (MRSA) strains, in mouse infection models. Specifically, we determined that naftifine is a lead compound for potent CrtN inhibitors. In sum, these findings reveal that naftifine could serve as a chemical probe to manipulate CrtN activity, providing proof of concept that CrtN is a druggable target against S. aureus infections.
资助项目	National Natural Science Foundation of China[21472207] ; National Natural Science Foundation of China[31270126] ; National Natural Science Foundation of China[21222211] ; National Natural Science Foundation of China[91313303] ; Hundred Talents Program of the Chinese Academy of Sciences[00000000] ; Shanghai Institute of Materia Medica Foundation[CASIMM0120152018] ; Shanghai Municipal Education Commission and Shanghai Education Development Foundation[14SG28] ; Foundation of the State Key Laboratory of Drug Research[SIMM1302KF-01] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2013ZX09507-004]
WOS关键词	RESISTANT STAPHYLOCOCCUS-AUREUS ; CAROTENOID BIOSYNTHETIC PATHWAYS ; STAPHYLOXANTHIN ; NAFTIFINE ; STRESS ; C-30
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000371377000010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276128]
专题	药理学第三研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Li, Jian; Lan, Lefu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 3.E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China; 4.Humanwell Healthcare Grp Co Ltd, Wuhan, Peoples R China;
推荐引用方式 GB/T 7714	Chen, Feifei,Di, Hongxia,Wang, Youxin,et al. Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence[J]. NATURE CHEMICAL BIOLOGY,2016,12(3):174-179.
APA	Chen, Feifei.,Di, Hongxia.,Wang, Youxin.,Cao, Qiao.,Xu, Bin.,...&Lan, Lefu.(2016).Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence.NATURE CHEMICAL BIOLOGY,12(3),174-179.
MLA	Chen, Feifei,et al."Small-molecule targeting of a diapophytoene desaturase inhibits S. aureus virulence".NATURE CHEMICAL BIOLOGY 12.3(2016):174-179.