Abstract
Carbapenem resistant Enterobacteriaceae are a significant public health concern, and genes encoding the Klebsiella pneumoniae carbapenemase (KPC) have contributed to the global spread of carbapenem resistance. In the current study, we used whole-genome sequencing to investigate the diversity of blaKPC-containing plasmids and antimicrobial resistance mechanisms among 26 blaKPC-containing Escherichia coli, and 13 blaKPC-containing Enterobacter asburiae, Enterobacter hormaechei, K. pneumoniae, Klebsiella variicola, Klebsiella michiganensis, and Serratia marcescens strains, which were isolated from the same patients as the blaKPC-containing E. coli. A blaKPC-containing IncN and/or IncFIIK plasmid was identified in 77% (30/39) of the E. coli and other bacterial species analyzed. Complete genome sequencing and comparative analysis of a blaKPC-containing IncN plasmid from one of the E. coli strains demonstrated that this plasmid is present in the K. pneumoniae and S. marcescens strains from this patient, and is conserved among 13 of the E. coli and other bacterial species analyzed. Interestingly, while both IncFIIK and IncN plasmids were prevalent among the strains analyzed, the IncN plasmids were more often identified in multiple bacterial species from the same patients, demonstrating a contribution of this IncN plasmid to the inter-genera dissemination of the blaKPC genes between the E. coli and other bacterial species analyzed.
Highlights
Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health concern as they are often multidrug-resistant, making them exceedingly difficult to treat[1,2,3,4,5,6,7,8,9,10,11]
The E. coli strains were isolated from at least seven different types of samples including Jackson-Pratt drainage, urine, sputum, blood, abdominal drainage/abdominal fistula, tracheal aspirate, and bronchoalveolar lavage (BAL) (Table 1). These E. coli strains were selected for genome sequencing because they were initially identified as carbapenem-resistant in the clinical microbiology laboratories, and were later determined to be PCR-positive for a blaKPC gene[21,22,37]
The other bacterial species analyzed were identified as E. asburiae, E. hormaechei, K. pneumoniae, K. variicola, K. michiganensis, S. marcescens, or P. stuartii, and were cultured from the same or a subsequent sample from the patients that had the blaKPC-containing E. coli strains (Tables 1 and 2)
Summary
Carbapenem-resistant Enterobacteriaceae (CRE) are a serious public health concern as they are often multidrug-resistant, making them exceedingly difficult to treat[1,2,3,4,5,6,7,8,9,10,11]. We used whole genome sequencing to characterize the diversity of all blaKPC-containing E. coli and any other blaKPC-containing bacterial species isolated from the same patients in a health system in Pennsylvania over time. This approach allowed us to investigate the diversity of mobile elements and antibiotic resistance genes carried by the blaKPC-containing E. coli among these patients, and characterize the intergenera transmission of blaKPC genes among the E. coli and other co-occurring bacterial species. Long-read sequencing was used to generate a complete genome assembly of a diverse blaKPC-containing E. coli strain, and examine the distribution of the 70-kb blaKPC-3-containing IncN multidrug resistance plasmid and two additional antibiotic resistance plasmids from this E. coli strain
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