Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia.
Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway.
J Antimicrob Chemother. 2019 May 1;74(5):1218-1222. doi: 10.1093/jac/dkz028.
MDR and hypervirulence (hv) are typically observed in separate Klebsiella pneumoniae populations. However, convergent strains with both properties have been documented and potentially pose a high risk to public health in the form of invasive infections with limited treatment options.
Our aim was to characterize the genetic determinants of virulence and antimicrobial resistance (AMR) in two ESBL-producing K. pneumoniae isolates belonging to the international MDR clone ST15.
The complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing.
Both isolates carried large mosaic plasmids in which AMR and virulence loci have converged within the same vector. These closely related mosaic hv-MDR plasmids include sequences typical of the K. pneumoniae virulence plasmid 1 (KpVP-1; including aerobactin synthesis locus iuc) fused with sequences typical of IncFIIK conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene blaCTX-M-15 and seven other AMR genes (blaTEM, aac3'-IIa, dfrA1, satA2, blaSHV, sul1 and aadA1). The other carried remnants of these elements encoding blaTEM and aac3'-IIa, and blaCTX-M-15 was located in a second plasmid in this isolate. The two isolates originated from patients hospitalized in Norway but have epidemiological and genomic links to Romania.
The presence of both virulence and AMR determinants on a single vector enables simultaneous transfer in a single event and potentially rapid emergence of hv-MDR K. pneumoniae clones. This highlights the importance of monitoring for such convergence events with stringent genomic surveillance.
耐多药（MDR）和超毒力（hv）通常在分开的肺炎克雷伯菌群体中观察到。然而，已经有具有这两种特性的趋同菌株被记录下来，它们以侵袭性感染的形式存在，治疗选择有限，对公共健康构成了高风险。
我们的目的是描述属于国际 MDR 克隆 ST15 的两株产 ESBL 的肺炎克雷伯菌分离株的毒力和抗菌药物耐药性（AMR）的遗传决定因素。
使用 Illumina 和 Oxford Nanopore 测序对这两种分离株的全基因组序列及其质粒进行解析。
两种分离株均携带大型镶嵌质粒，其中 AMR 和毒力基因在同一载体中融合。这些密切相关的镶嵌 hv-MDR 质粒包括肺炎克雷伯菌毒力质粒 1（KpVP-1；包括 aerobactin 合成基因座 iuc）的典型序列，与 IncFIIK 可接合性 AMR 质粒的典型序列融合。一个 hv-MDR 质粒携带三个编码 ESBL 基因 blaCTX-M-15 和其他七个 AMR 基因（blaTEM、aac3'-IIa、dfrA1、satA2、blaSHV、sul1 和 aadA1）的 MDR 元件。另一个携带这些编码 blaTEM 和 aac3'-IIa 的元件的残余物，而 blaCTX-M-15 位于该分离株中的第二个质粒上。这两种分离株来自在挪威住院的患者，但在流行病学和基因组上与罗马尼亚有关联。
单个载体上同时存在毒力和 AMR 决定因素，使得它们能够在单个事件中同时转移，并可能迅速出现 hv-MDR 肺炎克雷伯菌克隆。这突显了通过严格的基因组监测来监测这种趋同事件的重要性。
