Association of the Emerging Carbapenemase NDM-1 with a Bleomycin Resistance Protein in Enterobacteriaceae and Acinetobacter baumannii
Association of the Emerging Carbapenemase NDM-1 with a Bleomycin Resistance Protein in Enterobacteriaceae and Acinetobacter baumannii
复制标题
DOI：
10.1128/aac.05583-11
复制
发表时间：
2012-04-01
影响因子：
4.9
通讯作者：
Poirel, Laurent
中科院分区：
文献类型：
--
作者：
Dortet, Laurent;Nordmann, Patrice;Poirel, Laurent
最近在肠杆菌科和鲍曼不动杆菌中发现碳青霉烯酶NDM-1是多重耐药的来源，包括对碳青霉烯类的耐药。通过分析一系列产NDM-1肠杆菌分离株中bla（NDM-1）碳青霉烯酶基因的直接遗传环境，鉴定出一种新基因（ble（MBL），即与金属β-内酰胺酶NDM-1相关的ble基因）。ble（MBL）基因编码一种新的博来霉素抗性蛋白（BRP），命名为BRPMBL，其与已知的BRP具有弱相似性（小于60%的氨基酸同一性）。BRPMBL的表达使肠杆菌科和A.鲍曼不动杆菌。bla（NDM-1）和ble（MBL）基因在相同启动子的控制下共表达，所述启动子位于bla（NDM-1）基因的上游和插入序列ISAba 125的末端。大多数NDM产生者具有ble（MBL）基因。虽然BRPMBL在实验条件下不能改变大肠杆菌的生长或死亡率，但它抑制了超变大肠杆菌的突变率。因此，可以稳定质粒携带的bla（NDM-1）基因。这项研究表明，新兴的碳青霉烯酶NDM-1是由博莱霉素样分子选择的，BRPMBL生产者（因此NDM生产者）更适合于各种环境。
The carbapenemase NDM-1 has been identified recently in Enterobacteriaceae and Acinetobacter baumannii as a source of multidrug resistance, including resistance to carbapenems. By analyzing the immediate genetic environment of the bla(NDM-1) carbapenemase gene among a series of NDM-1-producing enterobacterial isolates, a novel gene (ble(MBL), for ble gene associated with the metallo-beta-lactamase NDM-1) was identified. The ble(MBL) gene encodes a novel bleomycin resistance protein (BRP), named BRPMBL, that shares weak similarities with known BRPs (less than 60% amino acid identity). The expression of BRPMBL conferred resistance to bleomycin and to bleomycin-like molecules in Enterobacteriaceae and A. baumannii. The bla(NDM-1) and ble(MBL) genes were coexpressed under the control of the same promoter, located upstream of the bla(NDM-1) gene and at the extremity of the insertion sequence ISAba125. Most of the NDM producers possessed the ble(MBL) gene. Although BRPMBL did not modify the growth or death rates of Escherichia coli under experimental conditions, it suppressed the mutation rate of hypermutable E. coli and therefore may stabilize the plasmid-borne bla(NDM-1) gene. This study suggests that the emerging carbapenemase NDM-1 is selected by bleomycin-like molecules, and that BRPMBL producers (and consequently NDM producers) are better suited to various environments.