Background: Carbapenem-resistant Klebsiella pneumoniae  infections have caused major concern and posed a global threat to public health. As bla_KPC-2  and bla_NDM-1  genes are the most widely reported carbapenem resistant genes in K. pneumonia , it is crucial to study the prevalence and geographical distribution of these two genes for further understanding of their transmission mode and mechanism.
Purpose: Here, we investigated the prevalence and distribution of bla_KPC-2  and bla_NDM-1  genes in carbapenem-resistant K. pneumoniae  strains from a tertiary hospital and from 1579 genomes available in the NCBI database, and further analyzed the possible core structure of bla_KPC-2  or bla_NDM-1  genes among global genome data.
Materials and Methods: K. pneumoniae  strains from a tertiary hospital in China during 2013– 2018 were collected and their antimicrobial susceptibility testing for 28 antibiotics was determined. Whole-genome sequencing of carbapenem-resistant K. pneumoniae  strains was used to investigate the genetic characterization. The phylogenetic relationships of these strains were investigated through pan-genome analysis. The epidemiology and distribution of bla_KPC-2  and bla_NDM-1  genes in K. pneumoniae  based on 1579 global genomes and carbapenem-resistant K. pneumoniae  strains from hospital were analyzed using bioinformatics. The possible core structure carrying bla_KPC-2  or bla_NDM-1  genes was investigated among global data.
Results: A total of 19 carbapenem-resistant K. pneumoniae  were isolated in a tertiary hospital. All isolates had a multi-resistant pattern and eight kinds of resistance genes. The phylogenetic analysis showed all isolates in the hospital were dominated by two lineages composed of ST11 and ST25, respectively. ST11 and ST25 were the major ST type carrying bla_KPC-2  and bla_NDM-1  genes, respectively. Among 1579 global genomes data, 147 known ST types (1195 genomes) have been identified, while ST258 (23.6%) and ST11 (22.1%) were the globally prevalent clones among the known ST types. Genetic environment analysis showed that the ISKpn7-dnaA/ISKpn27 -bla_KPC-2 -ISkpn6  and bla_NDM-1 -ble-trpf-nagA  may be the core structure in the horizontal transfer of bla_KPC-2  and bla_NDM-1 , respectively. In addition, DNA transferase (hin ) may be involved in the horizontal transfer or the expression of bla_NDM-1 .
Conclusion: There was clonal transmission of carbapenem-resistant K. pneumoniae  in the tertiary hospital in China. The prevalence and distribution of bla_KPC-2  and bla_NDM-1  varied by countries and were driven by different transposons carrying the core structure. This study shed light on the genetic environment of bla_KPC-2  and bla_NDM-1  and offered basic information about the mechanism of carbapenem-resistant K. pneumoniae  dissemination.
Keywords: Klebsiella pneumoniae , bla_KPC-2 , *bla_NDM-1 , bioinformatics