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

Kathryn E. Holt, Heiman Wertheim, Ruth N. Zadoks, Stephen Baker, Chris A. Whitehouse, David Dance, Adam Jenney, Thomas R. Connor, Li Yang Hsu, Juliëtte Severin, Sylvain Brisse, Hanwei Cao, Jonathan Wilksch, Claire Gorrie, Mark B. Schultz, David J. Edwards, Kinh Van Nguyen, Trung Vu Nguyen, Trinh Tuyet Dao, Martijn MensinkVien Le Minh, Nguyen Thi Khanh Nhu, Constance Schultsz, Kuntaman Kuntaman, Paul N. Newton, Catrin E. Moore, Richard A. Strugnell, Nicholas R. Thomson

Research output: Contribution to journalArticleResearchpeer-review

381 Citations (Scopus)

Abstract

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 genomewide 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 numerousmultidrug-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 languageEnglish
Pages (from-to)E3574-E3581
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number27
DOIs
Publication statusPublished - 7 Jul 2015
Externally publishedYes

Keywords

  • Antimicrobial resistance
  • Genomics
  • Klebsiella pneumoniae
  • Population structure
  • Virulence

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