Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health

被引:922
作者
Holt, Kathryn E. [1 ,2 ]
Wertheim, Heiman [3 ,4 ]
Zadoks, Ruth N. [5 ,6 ]
Baker, Stephen [7 ]
Whitehouse, Chris A. [8 ]
Dance, David [4 ,13 ]
Jenney, Adam [2 ,10 ,11 ]
Connor, Thomas R. [12 ,13 ]
Hsu, Li Yang [14 ]
Severin, Juliette [15 ]
Brisse, Sylvain [16 ]
Cao, Hanwei [2 ,17 ]
Wilksch, Jonathan [2 ,17 ]
Gorrie, Claire [1 ,2 ,17 ]
Schultz, Mark B. [1 ]
Edwards, David J. [1 ]
Kinh Van Nguyen [18 ]
Trung Vu Nguyen [18 ]
Trinh Tuyet Dao [18 ]
Mensinke, Martijn [5 ]
Vien Le Minh [7 ,19 ]
Nguyen Thi Khanh Nhu [7 ,20 ]
Schultsz, Constance [7 ,21 ]
Kuntaman, Kuntaman [22 ]
Newton, Paul N. [4 ,9 ]
Moore, Catrin E. [4 ,9 ]
Strugnell, Richard A. [2 ,17 ]
Thomson, Nicholas R. [12 ,23 ]
机构
[1] Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3010, Australia
[2] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia
[3] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Natl Hosp Trop Dis, Hanoi, Vietnam
[4] Univ Oxford, Ctr Trop Med, Nuffield Dept Clin Med, Oxford OX3 7BN, England
[5] Cornell Univ, Qual Milk Prod Serv, Ithaca, NY 14853 USA
[6] Univ Glasgow, Coll Med Vet & Life Sci, Institute Biodivers Anim Hlth & Comparat Med, Glasgow G12 8QQ, Lanark, Scotland
[7] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam
[8] US Army Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA
[9] Mahosot Hosp, Microbiol Lab, Lao Oxford Mahosot Hosp Wellcome Trust Res Unit, Viangchan, Laos
[10] Alfred Hosp, Dept Infect Dis, Melbourne, Vic 3004, Australia
[11] Alfred Hosp, Microbiol Unit, Melbourne, Vic 3004, Australia
[12] Wellcome Trust Sanger Ctr, Pathogen Genom, Cambridge CB10 1SA, England
[13] Cardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
[14] Natl Univ Hlth Syst, Dept Med, Singapore 119228, Singapore
[15] Erasmus Univ, Med Ctr, Dept Med Microbiol & Infect Dis, NL-3015 CE Rotterdam, Netherlands
[16] CNRS, UMR3525, Inst Pasteur, Microbial Evolutionary Genom, Paris, France
[17] Univ Melbourne, Peter Doherty Inst, Parkville, Vic 3010, Australia
[18] Natl Hosp Trop Dis, Hanoi, Vietnam
[19] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94118 USA
[20] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia
[21] Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands
[22] Airlangga Univ, Sch Med, Dr Soetomo Acad Hosp, Dept Clin Microbiol, Surabaya, Jawa Timur, Indonesia
[23] Univ London London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, London WC1E 7HT, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
Klebsiella pneumoniae; genomics; virulence; antimicrobial resistance; population structure; LIVER-ABSCESS; PHYLOGENETIC GROUPS; BETA-LACTAMASE; IDENTIFICATION; INFECTIONS; K1; EPIDEMIOLOGY; PREVALENCE; EVOLUTION; STRAINS;
D O I
10.1073/pnas.1501049112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Klebsiella pneumoniae is nowrecognized 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.
引用
收藏
页码:E3574 / E3581
页数:8
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