July 19, 2019  |  

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

Authors: Conlan, Sean and Thomas, Pamela J and Deming, Clayton and Park, Morgan and Lau, Anna F and Dekker, John P and Snitkin, Evan S and Clark, Tyson A and Luong, Khai and Song, Yi and Tsai, Yu-Chih and Boitano, Matthew and Dayal, Jyoti and Brooks, Shelise Y and Schmidt, Brian and Young, Alice C and Thomas, James W and Bouffard, Gerard G and Blakesley, Robert W and Mullikin, James C and Korlach, Jonas and Henderson, David K and Frank, Karen M and Palmore, Tara N and Segre, Julia A

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. Copyright © 2014, American Association for the Advancement of Science.

Journal: Science translational medicine
DOI: 10.1126/scitranslmed.3009845
Year: 2014

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