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Sci Transl Med. 2014 Sep 17;6(254):254ra126. doi: 10.1126/scitranslmed.3009845.

Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae.

Author information

1
National Human Genome Research Institute, Bethesda, MD 20892, USA.
2
National Institutes of Health Intramural Sequencing Center (NISC), Bethesda, MD 20852, USA.
3
National Institutes of Health Clinical Center, Bethesda, MD 20892, USA.
4
Pacific Biosciences, Menlo Park, CA 94025, USA.
5
National Institutes of Health Clinical Center, Bethesda, MD 20892, USA. karen.frank@nih.gov tpalmore@mail.nih.gov jsegre@nhgri.nih.gov.
6
National Human Genome Research Institute, Bethesda, MD 20892, USA. karen.frank@nih.gov tpalmore@mail.nih.gov jsegre@nhgri.nih.gov.

Abstract

Public health officials have raised concerns that plasmid transfer between Enterobacteriaceae species may spread resistance to carbapenems, an antibiotic class of last resort, thereby rendering common health care-associated infections nearly impossible to treat. To determine the diversity of carbapenemase-encoding plasmids and assess their mobility among bacterial species, we performed comprehensive surveillance and genomic sequencing of carbapenem-resistant Enterobacteriaceae in the National Institutes of Health (NIH) Clinical Center patient population and hospital environment. We isolated a repertoire of carbapenemase-encoding Enterobacteriaceae, including multiple strains of Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Enterobacter cloacae, Citrobacter freundii, and Pantoea species. Long-read genome sequencing with full end-to-end assembly revealed that these organisms carry the carbapenem resistance genes on a wide array of plasmids. K. pneumoniae and E. cloacae isolated simultaneously from a single patient harbored two different carbapenemase-encoding plasmids, indicating that plasmid transfer between organisms was unlikely within this patient. We did, however, find evidence of horizontal transfer of carbapenemase-encoding plasmids between K. pneumoniae, E. cloacae, and C. freundii in the hospital environment. Our data, including full plasmid identification, challenge assumptions about horizontal gene transfer events within patients and identify possible connections between patients and the hospital environment. In addition, we identified a new carbapenemase-encoding plasmid of potentially high clinical impact carried by K. pneumoniae, E. coli, E. cloacae, and Pantoea species, in unrelated patients and in the hospital environment.

PMID:
25232178
PMCID:
PMC4203314
DOI:
10.1126/scitranslmed.3009845
[Indexed for MEDLINE]
Free PMC Article

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