Mapping the Evolution of Hypervirulent Klebsiella pneumoniae.
Mapping the Evolution of Hypervirulent Klebsiella pneumoniae.
复制标题
DOI：
10.1128/mbio.00630-15
复制
发表时间：
2015-07-21
期刊：
影响因子：
6.4
通讯作者：
Krogfelt KA
中科院分区：
文献类型：
--
作者：
Struve C;Roe CC;Stegger M;Stahlhut SG;Hansen DS;Engelthaler DM;Andersen PS;Driebe EM;Keim P;Krogfelt KA
最近出现了高度侵袭性的社区获得性肺炎克雷伯菌感染，导致化脓性肝脓肿。这些感染由主要为荚膜血清型K1或K2的高毒力肺炎克雷伯菌（hvKP）分离株引起。高毒力K1菌株属于克隆复合体23（CC 23），表明该克隆谱系具有赋予高毒力的特定遗传背景。在这里，我们将全基因组测序应用于一组肺炎克雷伯菌分离株，以表征hvKP分离株的系统发育背景，重点是CC23。大多数的hvKP菌株属于CC23和分组到一个独特的单系分支，揭示了CC23是一个独特的克隆谱系，明显不同于非超毒力菌株。分离的CC23菌株的系统发育分析表明，CC23谱系进化最近从一个单一的共同祖先的克隆扩张。观察到根据地理来源进行的有限分组，表明CC23通过多次国际传播在全球传播。相反，高毒力K2菌株聚集在遗传上不相关的群体中。引人注目的是，在所有hvKP克隆谱系中检测到大毒力质粒的同源物，表明在肺炎克雷伯菌高毒力中起关键作用。该质粒编码两个铁载体，需氧肌动蛋白和salmochelin，和RmpA（调节粘液表型），所有这些因素被发现仅限于hvKP菌株。基因组比较揭示了与CC23特异性相关的其他因素。这些包括编码耶尔森菌素、大肠杆菌素和微菌素E492的基因组岛的不同变体。此外，还发现了CC23特有的其他新的基因组区域，这些区域也可能与这一重要克隆谱系的毒力增加有关。在过去的30年中，出现了高毒力肺炎克雷伯氏菌（hvKP）分离株，导致严重的社区获得性感染，主要表现为化脓性肝脓肿。迄今为止，这种综合征主要在东南亚发现，但世界各地报告的病例越来越多，表明这种综合征正在成为一种全球性的新兴疾病。我们对一组肺炎克雷伯菌临床分离株进行全基因组测序，以揭示hvKP的系统发育背景，并确定与毒力增加相关的遗传因素。hvKP分离株主要属于克隆复合物23（CC23），该克隆谱系被揭示为明显不同于非高毒力菌株。一个特定的毒力质粒被发现与高毒力，和新的遗传决定因素独特的CC23相关的被确定。我们的研究结果扩展了对hvKP克隆出现的遗传背景的理解。
Highly invasive, community-acquired Klebsiella pneumoniae infections have recently emerged, resulting in pyogenic liver abscesses. These infections are caused by hypervirulent K. pneumoniae (hvKP) isolates primarily of capsule serotype K1 or K2. Hypervirulent K1 isolates belong to clonal complex 23 (CC23), indicating that this clonal lineage has a specific genetic background conferring hypervirulence. Here, we apply whole-genome sequencing to a collection of K. pneumoniae isolates to characterize the phylogenetic background of hvKP isolates with an emphasis on CC23. Most of the hvKP isolates belonged to CC23 and grouped into a distinct monophyletic clade, revealing that CC23 is a unique clonal lineage, clearly distinct from nonhypervirulent strains. Separate phylogenetic analyses of the CC23 isolates indicated that the CC23 lineage evolved recently by clonal expansion from a single common ancestor. Limited grouping according to geographical origin was observed, suggesting that CC23 has spread globally through multiple international transmissions. Conversely, hypervirulent K2 strains clustered in genetically unrelated groups. Strikingly, homologues of a large virulence plasmid were detected in all hvKP clonal lineages, indicating a key role in K. pneumoniae hypervirulence. The plasmid encodes two siderophores, aerobactin and salmochelin, and RmpA (regulator of the mucoid phenotype); all these factors were found to be restricted to hvKP isolates. Genomic comparisons revealed additional factors specifically associated with CC23. These included a distinct variant of a genomic island encoding yersiniabactin, colibactin, and microcin E492. Furthermore, additional novel genomic regions unique to CC23 were revealed which may also be involved in the increased virulence of this important clonal lineage. During the last 3 decades, hypervirulent Klebsiella pneumoniae (hvKP) isolates have emerged, causing severe community-acquired infections primarily in the form of pyogenic liver abscesses. This syndrome has so far primarily been found in Southeast Asia, but increasing numbers of cases are being reported worldwide, indicating that the syndrome is turning into a globally emerging disease. We applied whole-genome sequencing to a collection of K. pneumoniae clinical isolates to reveal the phylogenetic background of hvKP and to identify genetic factors associated with the increased virulence. The hvKP isolates primarily belonged to clonal complex 23 (CC23), and this clonal lineage was revealed to be clearly distinct from nonhypervirulent strains. A specific virulence plasmid was found to be associated with hypervirulence, and novel genetic determinants uniquely associated with CC23 were identified. Our findings extend the understanding of the genetic background of the emergence of hvKP clones.