NDM-1 carbapenemase resistance gene vehicles emergent on distinct plasmid backbones from the IncL/M family
NDM-1 carbapenemase resistance gene vehicles emergent on distinct plasmid backbones from the IncL/M family
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DOI：
10.1093/jac/dkab466
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发表时间：
2022-02-23
影响因子：
5.2
通讯作者：
Ellington, Matthew J.
中科院分区：
文献类型：
--
作者：
Lopez-Diaz, Maria;Ellaby, Nicholas;Ellington, Matthew J.
目的评估英国卫生安全局抗菌药物耐药性和医疗保健相关感染（AMRHAI）参考单位6株产碳青霉烯酶肠球菌（CPE）分离株携带的IncM质粒上携带的bla（NDM-1）基因的遗传背景。方法在2014年至2018年期间，AMRHAI参考单位使用Illumina NGS对CPE分离株进行了WGS。将纳米孔测序用于选择的分离株，并下载公开可获得的质粒参考。对编码调节质粒repA基因表达的反义RNA的incRNA进行分析，并使用生物信息学工具分析整个质粒序列。结果在894株NDM阳性肠球菌中，有44株NDM-1阳性肠球菌，阴沟肠杆菌、大肠杆菌、肺炎克雷伯菌和产酸克雷伯菌）编码IncM 2质粒的IncRNA基因座。6个不同分离株的长读段测序显示相关的IncM 2、NDM-1编码质粒。质粒“骨架”区域是保守的，并与高度可变的抗性区域形成对比。检测编码bla（NDM-1）的IncM 2质粒的亚组;一个亚组每年发生在英格兰的五个不同的健康地区。NDM-1基因整合子和转座子及其插入位点的多样性表明，NDM-1已被IncM 2变异体重复获得。结论测序的使用有助于提供以下信息：（i）在紧急IncM 2质粒上编码NDM-1的分离株的广泛地理分布;（ii）变异质粒已单独获得NDM-1;以及（iii）该质粒组中耐药元件的动态排列和进化。编码NDM-1的IncM 2质粒的地理和时间分布突出表明它们是一种公共卫生威胁，需要持续监测。
Objectives To assess the genetic contexts surrounding bla(NDM-1) genes carried on IncM plasmids harboured by six carbapenemase-producing Enterobacterales (CPE) isolates referred to the UK Health Security Agency's Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit. Methods Between 2014 and 2018, the AMRHAI Reference Unit undertook WGS of CPE isolates using Illumina NGS. Nanopore sequencing was used for selected isolates and publicly available plasmid references were downloaded. Analysis of incRNA, which encodes the antisense RNA regulating plasmidic repA gene expression, was performed and bioinformatics tools were used to analyse whole plasmid sequences. Results Of 894 NDM-positive isolates of Enterobacterales, 44 NDM-1-positive isolates of five different species (Citrobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca) encoded the IncRNA locus of IncM2 plasmids. Long-read sequencing of six diverse isolates revealed related IncM2, NDM-1-encoding plasmids. Plasmid 'backbone' areas were conserved and contrasted with highly variable resistance regions. Sub-groupings of IncM2 plasmids encoding bla(NDM-1) were detected; one sub-group occurred in five different health regions of England in every year. The diversity of NDM-1-encoding resistance gene integrons and transposons and their insertions sites in the plasmids indicated that NDM-1 has been acquired repeatedly by IncM2 variants. Conclusions The use of sequencing helped inform: (i) a wide geographical distribution of isolates encoding NDM-1 on emergent IncM2 plasmids; (ii) variant plasmids have acquired NDM-1 separately; and (iii) dynamic arrangements and evolution of the resistance elements in this plasmid group. The geographical and temporal distribution of IncM2 plasmids that encode NDM-1 highlights them as a public health threat that requires ongoing monitoring.