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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.

Original publication

DOI

10.1073/pnas.1501049112

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

07/2015

Volume

112

Pages

E3574 - E3581

Addresses

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; nrt@sanger.ac.uk kholt@unimelb.edu.au.

Keywords

Animals, Humans, Klebsiella pneumoniae, Klebsiella Infections, Cross Infection, Bacterial Proteins, Anti-Infective Agents, Sequence Analysis, DNA, Genomics, Public Health, Population Dynamics, Phylogeny, Drug Resistance, Multiple, Bacterial, Virulence, Species Specificity, Genes, Bacterial, Genome, Bacterial, Genetic Variation