Holt Kathryn E, Wertheim Heiman, Zadoks Ruth N, Baker Stephen, Whitehouse Chris A, Dance David, Jenney Adam, Connor Thomas R, Hsu Li Yang, Severin Juliëtte, Brisse Sylvain, Cao Hanwei, Wilksch Jonathan, Gorrie Claire, Schultz Mark B, Edwards David J, Nguyen Kinh Van, Nguyen Trung Vu, Dao Trinh Tuyet, Mensink Martijn, Minh Vien Le, Nhu Nguyen Thi Khanh, Schultsz Constance, Kuntaman Kuntaman, Newton Paul N, Moore Catrin E, Strugnell Richard A, Thomson Nicholas R
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia;
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, National Hospital for Tropical Diseases, Hanoi, Vietnam; Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, OX3 7BN Oxford, United Kingdom;
Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):E3574-81. doi: 10.1073/pnas.1501049112. Epub 2015 Jun 22.
Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.
肺炎克雷伯菌现已被视为对人类健康的紧迫威胁,因为出现了与医院暴发相关的多重耐药菌株以及与严重社区获得性感染相关的高毒力菌株。肺炎克雷伯菌在环境中无处不在,可在植物和动物体内定殖并感染它们。然而,人们对肺炎克雷伯菌的种群结构知之甚少,因此很难识别或理解在这个遗传高度多样的物种中临床重要克隆的出现。在此,我们基于对来自四大洲的300多株人类和动物分离株进行全基因组测序,提出了一个详细的肺炎克雷伯菌基因组框架。我们的数据为将肺炎克雷伯菌分为三个不同的物种提供了全基因组支持,即KpI(肺炎克雷伯菌)、KpII(准肺炎克雷伯菌)和KpIII(多变克雷伯菌)。此外,对于肺炎克雷伯菌(KpI),即最常与人类感染相关的实体,我们发现存在超过150个深度分支谱系,包括许多多重耐药或高毒力克隆。我们表明,肺炎克雷伯菌有一个庞大的辅助基因组,接近30,000个蛋白质编码基因,其中包括一些与人类侵袭性社区获得性疾病显著相关的毒力功能。在我们的数据集中,抗菌耐药基因在人类携带分离株和医院获得性感染中很常见,而这些感染通常缺乏与侵袭性疾病相关的基因。毒力和耐药基因的趋同可能会导致无法治疗的侵袭性肺炎克雷伯菌感染的出现;我们的数据提供了一个全基因组框架,可据此追踪此类威胁的出现。