Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae

Sophia David, Victoria Cohen, Sandra Reuter, Anna E. Sheppard, Tommaso Giani, Julian Parkhill, Gian Maria Rossolini, Edward J. Feil, Hajo Grundmann, David M. Aanensen

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with lowresolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, blaOXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, blaVIM and blaNDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, blaKPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying blaKPC. Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.

Original languageEnglish
Pages (from-to)25043-25054
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number40
Early online date23 Sep 2020
DOIs
Publication statusPublished - 6 Oct 2020

Keywords

  • Carbapenem resistance
  • Carbapenemase genes
  • Genomics
  • Klebsiella pneumoniae
  • Plasmids

ASJC Scopus subject areas

  • General

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