Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae
Journal
The Proceedings of the National Academy of Sciences (PNAS)
Date Issued
2020-10
Author(s)
Sophia David
Victoria Cohen
Sandra Reuter
The European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) Working Group
DOI
10.1073/pnas.2003407117
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.
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.
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