LMB-1, a novel family of class B3 MBLs from an isolate of Enterobacter cloacae
LMB-1, a novel family of class B3 MBLs from an isolate of Enterobacter cloacae
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DOI：
10.1093/jac/dky215
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发表时间：
2018-09-01
影响因子：
5.2
通讯作者：
Kaase, Martin
中科院分区：
文献类型：
--
作者：
Lange, Felix;Pfennigwerth, Niels;Kaase, Martin
目的：目的：鉴定和鉴定一种新的MBL基因，该基因可使奥地利产阴沟肠杆菌对碳青霉烯类抗生素产生耐药性。方法：将新的MBL基因在大肠杆菌TOP10中异源表达，并进行比较MIC研究和生化分析。结果：该新MBL基因与海洋细菌太平洋莱茵海默菌（Rheinheimera pacifica）的MBL前体序列同源性最高，属于Ambler亚群B3。比较MIC研究和生化测定显示新酶对青霉素类、头孢菌素类和碳青霉烯类的活性，但对氨曲南没有活性。它被命名为林茨MBL（LMB-1）。bla（LMB-1）基因显示位于Inc型IncFIB（K）的108 kb质粒上。值得注意的是，与bla（LMB-1）相邻的基因编码甘油磷酸二酯磷酸二酯酶，该酶以前也在R. pacifica.Conclusions:MBL基因本身和位于同一质粒上的另一个基因与海洋细菌中检测到的基因的同源性强有力地表明，这种新的MBL被转移到E。从海洋细菌中分离出来的。这强调了天然储存库为临床相关细菌物种提供迄今未知的耐药基因的重要性，以及持续监测和研究的重要性。
Objectives: To identify and characterize a novel MBL gene conferring carbapenem resistance to an isolate of Enterobacter cloacae from Austria.Methods: The novel MBL gene was heterologously expressed in Escherichia coli TOP10 to conduct comparative MIC studies and biochemical assays. Furthermore, WGS was performed using Illumina MiSeq and Oxford Nanopore MinION instruments to analyse the genetic environment of the novel MBL gene.Results: The novel MBL showed highest sequence homology to a predicted MBL precursor from the marine bacterium Rheinheimera pacifica and hence belongs to Ambler subgroup B3. The comparative MIC studies and biochemical assays showed activity of the novel enzyme against penicillins, cephalosporins and carbapenems, but not against aztreonam. It was named Linz MBL (LMB-1). The bla(LMB-1) gene was shown to be located on a 108 kb plasmid of Inc type IncFIB(K). Of note, a gene adjacent to bla(LMB-1) coded for a glycerophosphoryl diester phosphodiesterase that was also previously detected in R. pacifica.Conclusions: Homologies of the MBL gene itself and another gene located on the same plasmid to genes detected in marine bacterial species strongly suggest that this novel MBL was transferred to E. cloacae from a marine bacterium. This underlines the importance of natural reservoirs supplying hitherto unknown resistance genes to clinically relevant bacterial species and the importance of ongoing surveillance and research.