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学科主题临床医学
Genetic characterisation of clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline: Role of the global regulator RamA and its local repressor RamR
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
2015-06-01
DOI10.1016/j.ijantimicag.2014.12.022
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
WOS记录号WOS:000354569400012
项目编号5122041 ; 20110001110043 ; KZ201210025025 ; NCET-10-0205
资助机构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
引用统计
被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58101
专题北京大学第二临床医学院
北京大学第二临床医学院_检验科
作者单位Peking Univ, Peoples Hosp, Dept Clin Lab, Beijing 100044, Peoples R China
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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.
APA Wang, Xiaojuan.,Chen, Hongbin.,Zhang, Yawei.,Wang, Qi.,Zhao, Chunjiang.,...&Wang, Hui.(2015).Genetic characterisation of clinical Klebsiella pneumoniae isolates with reduced susceptibility to tigecycline: Role of the global regulator RamA and its local repressor RamR.INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,45(6),635-640.
MLA Wang, Xiaojuan,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".INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 45.6(2015):635-640.
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