Abstract
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.