Molecular characterization and comparison of blaNDM-1-carrying and blaNDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae

[摘要] ABSTRACTCarbapenem-resistant Klebsiella pneumoniae (CRKP), which harbors the blaNDM plasmid, has been reported extensively and is considered a global threat clinically. However, characterization and comparisons of blaNDM-1-carrying and blaNDM-5-harboring IncX3-type plasmids in CRKP are lacking. Here, we systematically compared the differences in the characteristics, genetic backgrounds, transferability, and fitness costs between blaNDM-1-carrying and blaNDM-5-carrying plasmids in K. pneumoniae isolates. Fifteen NDM-producing CRKP isolates were recovered from 1376 CRKP isolates between 2019 and 2021, of which 4 were positive for blaNDM-1 and 11 were positive for blaNDM-5. All strains were highly resistant to carbapenem but remained susceptible to tigecycline and colistin. Core-genome-based phylogenetic analyses revealed that these strains were not clonally related. Whole-genome sequencing showed that blaNDM-1 and blaNDM-5 were located on ~54 kb and ~46 kb IncX3-type plasmids, respectively. The backbone, genetic context, and fitness cost of the blaNDM-1-bearing plasmid were highly similar to those of the blaNDM-5-carrying plasmid, but the transferability of the blaNDM-1-positive plasmid was greater than that of the blaNDM-5-positive plasmid. In conclusion, the transmission of blaNDM-1 or blaNDM-5 is mainly disseminated by plasmids rather than clonal spread. The high transfer frequency of the IncX3 plasmid facilitates the prevalence and dissemination of NDM-KP among Enterobacteriaceae.IMPORTANCEThe emergence of NDM-producing Klebsiella pneumoniae is a severe challenge to public health. The widespread presence of blaNDM-1 and blaNDM-5 in Enterobacteriaceae has aroused broad concern. In this study, we performed molecular characterization of blaNDM-1-carrying and blaNDM-5-harboring IncX3-type plasmids in carbapenem-resistant Klebsiella pneumoniae (CRKP) and compared their phenotypes between strains with different blaNDM subtype. Our findings highlight the importance of IncX3-type plasmids in the transfer of the blaNDM-1 and blaNDM-5 genes and demonstrate that the blaNDM-1 plasmid possesses higher transfer ability. These data will provide important insights into carbapenem resistance gene transfer via plasmids and their further spread in clinical settings.

[发布日期] 2023-10-17

[关键词] carbapenemases;NDM-1;NDM-5;IncX3;fitness