北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第二临床医学院  > 期刊论文
学科主题: 临床医学
题名:
Genetic characterisation of clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline: Role of the global regulator RamA and its local repressor RamR
作者: Wang, Xiaojuan; Chen, Hongbin; Zhang, Yawei; Wang, Qi; Zhao, Chunjiang; Li, Henan; He, Wenqiang; Zhang, Feifei; Wang, Zhanwei; Li, Shuguang; Wang, Hui
关键词: Tigecycline ; Klebsiella pneumoniae ; ramA ; ramR ; marA
刊名: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
发表日期: 2015-06-01
DOI: 10.1016/j.ijantimicag.2014.12.022
卷: 45, 期:6, 页:635-640
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
研究领域[WOS]: Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
关键词[WOS]: DECREASED SUSCEPTIBILITY ; EFFLUX PUMP ; RESISTANCE ; EXPRESSION ; ACRAB ; MARA
英文摘要:

Laboratory-derived Klebsiellapneumoniae mutants demonstrated that the ramA locus mediated low-level tigecycline resistance. The aim of this study was to elucidate the underlying mechanisms of tigecydine resistance in clinical K. pneumoniae isolates. In total, 106 isolates with tigecycline MICs ranging from 0.125 mg/L to 16 mg/L were collected to determine the correlations between expression of the global regulon ramA, marA, soxS, the acrB pump gene and tigecycline MICs. PCR was used to determine whether mutations in ramR, acrR or the rpsJ gene encoding 30S ribosomal protein S10 were responsible for tigecycline resistance. ramA or ramR inactivation and corresponding trans-complemented strains were used to characterise the contribution of RamA and RamR to tigecycline resistance. Tigecycline MICs were correlated with transcriptional levels of ramA and acrB, but were negatively correlated with marA and soxS. Disrupting ramA strikingly reduced the tigecycline MIC by 16-fold, accompanied by a 0.5-fold downregulation of acrB expression and 3.14- and 3.80-fold upregulation of marA and soxS, respectively. Complementation with plasmid-borne ramA restored the original parental phenotype of decreased tigecycline susceptibility. Of 34 tigecycline-non-susceptible isolates, 21 harbouring diverse mutations in RamR led to ramA overexpression. Disrupting the mutated ramR gene and complementing the mutated ramR gene with a wild-type gene downregulated expression of ramA but maintained the same tigecycline-resistant phenotype as the parental strain; the complemented strain exhibited 4.21- and 27.51-fold increased expression of acrB and marA, respectively. In conclusion, for the majority of tigecycline-resistant K. pneumoniae, ramA, depressed by ramR, was the major factor accounting for tigecycline resistance. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

语种: 英语
所属项目编号: 5122041 ; 20110001110043 ; KZ201210025025 ; NCET-10-0205
项目资助者: Beijing Natural Science Foundation ; Research Fund for the Doctoral Program of Higher Education of China (RFDP) ; Beijing City Board of Education Science and Technology key project ; Trans-Century Training Programme Foundation for the Talents by the State Education Commission
WOS记录号: WOS:000354569400012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58101
Appears in Collections:北京大学第二临床医学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: Peking Univ, Peoples Hosp, Dept Clin Lab, Beijing 100044, Peoples R China

Recommended Citation:
Wang, Xiaojuan,Chen, Hongbin,Zhang, Yawei,et al. Genetic characterisation of clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline: Role of the global regulator RamA and its local repressor RamR[J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,2015,45(6):635-640.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Wang, Xiaojuan]'s Articles
[Chen, Hongbin]'s Articles
[Zhang, Yawei]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Wang, Xiaojuan]‘s Articles
[Chen, Hongbin]‘s Articles
[Zhang, Yawei]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace