Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2

doi:10.1016/j.cclet.2019.07.063

	Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2
	Zheng, Xinyu 1; Cao, Qiao 2; Cao, Qin 2; Mao, Fei 1; Li, Xiaokang 1; Zhu, Jin 1; Lan, Lefu 2; Li, Jian 1
刊名	CHINESE CHEMICAL LETTERS
	2020-02-01
卷号	31 期号:2 页码:413-417
关键词	Polymyxin B Pseudomonas aeruginosa Fluoroquinolones Synergy Cystic fibrosis Antimicrobial peptides
ISSN号	1001-8417
DOI	10.1016/j.cclet.2019.07.063
通讯作者	Zhu, Jin(jinz@ecust.edu.cn) ; Lan, Lefu(llan@simm.ac.cn) ; Li, Jian(jianli@ecust.edu.cn)
英文摘要	Polymyxin B (PB), as the last-line of defense against multidrug-resistant Gram-negative bacteria, has caused resistance to P. aeruginosa recently. Fortunately, synergistic treatment could preserve the last class of antibiotics and reduce the emergency of drug resistance. Here, we performed a screen of 970 approved drugs synergized with PB against the P. aeruginosa DK2, which is severely resistant to PB, MIC = 512 mu g/mL. Encouragingly, we found fluoroquinolones could synergy with PB and achieved an obvious reduction in MIC of PB below the clinical susceptible breakpoint (2 mu g/mL). Especially, gemifloxacin achieved the highest synergistic effect with PB, leading to a 4096-fold MIC reduction (reduced from 512 mu g/mL to 0.125 mu g/mL). Furthermore, synergistic effect was also observed in the combination of gemifloxacin and colistin. Finally, outer membrane permeabilization assay showed that gemifloxacin could increase the permeability of bacterial cell membranes for P. aeruginosa which partly explained the synergy mechanism. These results indicate that fluoroquinolones represent attractive synergists to address the emerging threat of polymyxin-resistant infections. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
资助项目	National Key R&D Program of China[2017YFB0202600] ; National Natural Science Foundation of China[21672064] ; National Natural Science Foundation of China[21702061] ; National Natural Science Foundation of China[81861138047] ; Innovative Research Team of High-level Local Universities in Shanghai ; National Special Fund for State Key Laboratory of Bioreactor Engineering[2060204] ; Shanghai Municipal Education Commission ; Shanghai Education Development Foundation[14SG28] ; Shanghai Sailing Program[17YF1403600]
WOS关键词	ANTIBIOTICS ; ADAPTATION
WOS研究方向	Chemistry
语种	英语
出版者	ELSEVIER SCIENCE INC
WOS记录号	WOS:000510956700024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281598]
专题	中国科学院上海药物研究所
通讯作者	Zhu, Jin; Lan, Lefu; Li, Jian
作者单位	1.East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zheng, Xinyu,Cao, Qiao,Cao, Qin,et al. Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2[J]. CHINESE CHEMICAL LETTERS,2020,31(2):413-417.
APA	Zheng, Xinyu.,Cao, Qiao.,Cao, Qin.,Mao, Fei.,Li, Xiaokang.,...&Li, Jian.(2020).Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2.CHINESE CHEMICAL LETTERS,31(2),413-417.
MLA	Zheng, Xinyu,et al."Discovery of synergistic activity of fluoroquinolones in combination with antimicrobial peptides against clinical polymyxin-resistant Pseudomonas aeruginosa DK2".CHINESE CHEMICAL LETTERS 31.2(2020):413-417.