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

文献类型：期刊论文

作者Chen, Feifei2; Di, Hongxia2; Wang, Youxin3; Cao, Qiao2; Xu, Bin2; Zhang, Xue2; Yang, Nana2; Liu, Guijie2; Yang, Cai-Guang2; Xu, Yong4
刊名NATURE CHEMICAL BIOLOGY
出版日期2016-03
卷号12期号:3页码:174-179
ISSN号1552-4450
DOI10.1038/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.
WOS关键词RESISTANT STAPHYLOCOCCUS-AUREUS ; CAROTENOID BIOSYNTHETIC PATHWAYS ; STAPHYLOXANTHIN ; NAFTIFINE ; STRESS ; C-30
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研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000371377000010
出版者NATURE PUBLISHING GROUP
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.

入库方式： OAI收割

来源：上海药物研究所

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