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德国发现新型新德里金属β-内酰胺酶 NDM-7,其碳青霉烯酶活性增强。

Detection of NDM-7 in Germany, a new variant of the New Delhi metallo-β-lactamase with increased carbapenemase activity.

机构信息

Institute for Medical Microbiology and Infection Control, Hospital of Goethe-University, Frankfurt am Main, Germany.

出版信息

J Antimicrob Chemother. 2013 Aug;68(8):1737-40. doi: 10.1093/jac/dkt088. Epub 2013 Apr 3.

Abstract

OBJECTIVES

This study characterized a new variant of the New Delhi metallo-β-lactamase (NDM).

METHODS

A multidrug-resistant Escherichia coli isolate was recovered from the wounds, throat and rectum of a Yemeni patient who presented at the Frankfurt University Hospital in Germany. The presence of β-lactamase genes was analysed by PCR and sequencing. The isolate was further characterized by susceptibility testing, conjugation and transformation assays and plasmid analysis.

RESULTS

The E. coli isolate was resistant to all β-lactams including carbapenems. By PCR analysis, the β-lactamase genes blaCMY-2, blaCTX-M-15, blaTEM-1 and blaNDM were identified. Sequencing revealed a blaNDM gene that differed from blaNDM-1 by two point mutations at positions 388 (G→A) and 460 (A→C) corresponding to amino acid substitutions Asp130Asn and Met154Leu, respectively. This NDM variant was identified as NDM-7. The blaNDM-7 gene was located on a self-transferable IncX3 plasmid of 60 kb. E. coli TOP10 transformants harbouring NDM-7 showed higher MICs of β-lactams including carbapenems compared with transformants harbouring NDM-1. Multilocus sequence typing analysis revealed that the E. coli isolate belonged to a novel sequence type (ST599).

CONCLUSIONS

This study identified a novel NDM variant in E. coli, NDM-7, possessing a high ability to hydrolyse β-lactam antibiotics. Given the diversity of NDM variants located on self-transferable plasmids found in different Gram-negative species and isolated in different countries, the blaNDM gene will most likely efficiently disseminate worldwide.

摘要

目的

本研究对一种新型新德里金属β-内酰胺酶(NDM)变体进行了特征描述。

方法

从一名在德国法兰克福大学医院就诊的也门患者的伤口、喉咙和直肠中分离出一株多药耐药性大肠杆菌。通过 PCR 和测序分析β-内酰胺酶基因的存在。通过药敏试验、接合和转化试验以及质粒分析对分离株进行进一步鉴定。

结果

大肠杆菌分离株对所有β-内酰胺类药物(包括碳青霉烯类)均具有耐药性。通过 PCR 分析,鉴定出 blaCMY-2、blaCTX-M-15、blaTEM-1 和 blaNDM 等β-内酰胺酶基因。测序显示 blaNDM 基因与 blaNDM-1 有两个点突变,分别位于 388 位(G→A)和 460 位(A→C),导致相应的氨基酸取代为 Asp130Asn 和 Met154Leu。该 NDM 变体被鉴定为 NDM-7。blaNDM-7 基因位于一个可自我转移的 60kb IncX3 质粒上。携带 NDM-7 的大肠杆菌 TOP10 转化子对β-内酰胺类药物(包括碳青霉烯类)的 MICs 明显高于携带 NDM-1 的转化子。多位点序列分型分析显示,大肠杆菌分离株属于一种新型序列型(ST599)。

结论

本研究在大肠杆菌中发现了一种新型 NDM 变体 NDM-7,该变体具有高效水解β-内酰胺类抗生素的能力。鉴于不同革兰氏阴性菌和不同国家分离出的可自我转移质粒上存在多种 NDM 变体,blaNDM 基因很可能会在全球范围内有效传播。

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