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

Holt, Kathryn E., Wertheim, Heiman, Zadoks, Ruth N., Baker, Stephen, Whitehouse, Chris A., Dance, David, Jenney, Adam, Connor, Thomas R., Hsu, Li Yang, Severin, Juliette, Brisse, Sylvain, Cao, Hanwei, Wilksch, Jonathan, Gorrie, Claire, Schultz, Mark B., Edwards, David J., Van Nguyen, Kinh, Nguyen, Trung Vu, Dao, Trinh Tuyet, Mensink, Martijn, Le Minh, Vien, Nhu, Nguyen Thi Khanh, Schultsz, Constance, Kuntaman K., Newton P.N., Moore C.E., Strugnell R.A. and Thomson N.R. (2015) Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proceedings of the National Academy of Sciences of the United States of America, 112 27: E3574-E3581. doi:10.1073/pnas.1501049112


Author Holt, Kathryn E.
Wertheim, Heiman
Zadoks, Ruth N.
Baker, Stephen
Whitehouse, Chris A.
Dance, David
Jenney, Adam
Connor, Thomas R.
Hsu, Li Yang
Severin, Juliette
Brisse, Sylvain
Cao, Hanwei
Wilksch, Jonathan
Gorrie, Claire
Schultz, Mark B.
Edwards, David J.
Van Nguyen, Kinh
Nguyen, Trung Vu
Dao, Trinh Tuyet
Mensink, Martijn
Le Minh, Vien
Nhu, Nguyen Thi Khanh
Schultsz, Constance
Kuntaman K.
Newton P.N.
Moore C.E.
Strugnell R.A.
Thomson N.R.
Title Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 1091-6490
0027-8424
Publication date 2015-07-07
Sub-type Article (original research)
DOI 10.1073/pnas.1501049112
Open Access Status Not Open Access
Volume 112
Issue 27
Start page E3574
End page E3581
Total pages 8
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Subject 1000 General
Abstract 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.
Formatted abstract
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.
Keyword Antimicrobial resistance
Genomics
Klebsiella pneumoniae
Population structure
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 089276
100087
089275/H/09/Z
098051
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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