Embelin Restores Carbapenem Efficacy against NDM-1-Positive Pathogens

doi:10.3389/fmicb.2018.00071

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	Embelin Restores Carbapenem Efficacy against NDM-1-Positive Pathogens
	Ning, Nian-Zhi 2; Liu, Xiong 2; Chen, Fanghong 2; Zhou, Peng 1,3; Hu, Lihong 4; Huang, Jian 1,3; Li, Zhan 2; Huang, Jie 2; Li, Tao 2; Wang, Hui 2
刊名	FRONTIERS IN MICROBIOLOGY
	2018-01-25
卷号	9
关键词	embelin carbapenem NDM-1 carbapenemase inhibitor
ISSN号	1664-302X
DOI	10.3389/fmicb.2018.00071
文献子类	Article
英文摘要	The emergence and spread of carbapenemase in Gram-negative pathogens poses an enormous threat to global public health. New Delhi metallo-beta-lactamase-1 (NDM-1) inactivates nearly every class of beta-lactam antibiotics, including carbapenem; however, there is no clinically useful NDM-1 inhibitor. Embelin, an important ingredient in traditional herbal medicine, has anti-tumor effects. The current study is the first to discover and examine the inhibitory activity of embelin against beta-lactamase NDM-1. The IC50 of embelin was 2.1 +/- 0.2 mu M when tested against NDM-1 carbapenemase. Most regions of the embelin molecule were buried within NDM-1's active site, and the hydroxyl group of embelin interacted directly with the metal ion Zn2+ as shown by molecular dynamic simulation. Systematic analysis of the antibacterial activities of embelin and antibiotics demonstrated that embelin restored meropenem activity against a panel of NDM-positive pathogens, such as Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Based on these results, embelin could be a promising carbapenem adjuvant candidate against NDM-1-producing bacterial strains.
资助项目	National Key Basic Research Program (973) of China[2015CB554202] ; National Natural Science Foundation of China[81401643] ; State Key Research Development Program of China[2016YFC1200301] ; State Key Laboratory of Pathogen and BioSecurity Program[SKLPBS1506] ; State Key Laboratory of Pathogen and BioSecurity Program[SKLPBS1530] ; State Key Laboratory of Pathogen and BioSecurity Program[SKLPBS1424] ; Beijing Nova Program[XX2018043]
WOS关键词	METALLO-BETA-LACTAMASE ; ANTIBIOTIC-RESISTANCE ; LIGAND INTERACTIONS ; GLOBAL SPREAD ; PROTEIN ; INHIBITORS ; ENTEROBACTERIACEAE ; DISCOVERY ; MEDICINE ; DOCKING
WOS研究方向	Microbiology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000423364900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279946]
专题	上海中药现代化研究中心
通讯作者	Li, Tao; Wang, Hui
作者单位	1.Univ Elect Sci & Technol China, Ctr Informat Biomed, Chengdu, Sichuan, Peoples R China; 2.Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogens & Biosecur, Beijing, Peoples R China; 3.Univ Elect Sci & Technol China, Minist Educ, Key Lab NeuroInformat, Chengdu, Sichuan, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Ning, Nian-Zhi,Liu, Xiong,Chen, Fanghong,et al. Embelin Restores Carbapenem Efficacy against NDM-1-Positive Pathogens[J]. FRONTIERS IN MICROBIOLOGY,2018,9.
APA	Ning, Nian-Zhi.,Liu, Xiong.,Chen, Fanghong.,Zhou, Peng.,Hu, Lihong.,...&Wang, Hui.(2018).Embelin Restores Carbapenem Efficacy against NDM-1-Positive Pathogens.FRONTIERS IN MICROBIOLOGY,9.
MLA	Ning, Nian-Zhi,et al."Embelin Restores Carbapenem Efficacy against NDM-1-Positive Pathogens".FRONTIERS IN MICROBIOLOGY 9(2018).