Horizontal Transfer of Carbapenemase-Encoding Plasmids and Comparison with Hospital Epidemiology Data

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Abstract
Carbapenemase-producing organisms have spread worldwide, and infections with these bacteria cause significant morbidity. Horizontal transfer of plasmids carrying genes that encode carbapenemases plays an important role in the spread of multidrug-resistant Gram-negative bacteria. Here we investigate parameters regulating conjugation using an Escherichia coli laboratory strain that lacks plasmids or restriction enzyme modification systems as a recipient and also using patient isolates as donors and recipients. Because conjugation is tightly regulated, we performed a systematic analysis of the transfer of Klebsiella pneumoniae carbapenemase ( bla KPC )-encoding plasmids into multiple strains under different environmental conditions to investigate critical variables. We used four bla KPC -carrying plasmids isolated from patient strains obtained from two hospitals: pKpQIL and pKPC-47e from the National Institutes of Health, and pKPC_UVA01 and pKPC_UVA02 from the University of Virginia. Plasmid transfer frequency differed substantially between different donor and recipient pairs, and the frequency was influenced by plasmid content, temperature, and substrate, in addition to donor and recipient strain. pKPC-47e was attenuated in conjugation efficiency across all conditions tested. Despite its presence in multiple clinical species, pKPC_UVA01 had lower conjugation efficiencies than pKpQIL into recipient strains. The conjugation frequency of these plasmids into K. pneumoniae and E. coli patient isolates ranged widely without a clear correlation with clinical epidemiological data. Our results highlight the importance of each variable examined in these controlled experiments. The in vitro models did not reliably predict plasmid mobilization observed in a patient population, indicating that further studies are needed to understand the most important variables affecting horizontal transfer in vivo .
Funding Information
  • Biotechnology and Biological Sciences Research Council
  • National Institutes of Health Director's Challenge Innovation Award
  • NIHR Oxford Biomedical Research Centre
  • Wellcome Trust (087646/Z/08/Z)
  • HHS | NIH | National Human Genome Research Institute
  • Medical Research Council
  • DH | National Institute for Health Research (G0800778)
  • HHS | NIH | NIH Clinical Center

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