In silico characterization of bla NDM-harboring plasmids in Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae is a primary culprit of antibiotic-resistant nosocomial infections worldwide, and infections caused by NDM-producing strains are a major threat due to limited therapeutic options. The majority of bla _NDM cases occur on plasmids; therefore, we explored the relationships between plasmids and bla _NDM genes in K. pneumoniae by analyzing the variants of bla _NDM, replicon types, conjugative transfer regions of 171 bla _NDM-harboring plasmids from 4,451 K. pneumoniae plasmids. Of the nine identified bla _NDM variants, bla _NDM-1 (73.68%) and bla _NDM-5 (16.37%) were the most dominant. Over half of the bla _NDM-harboring plasmids of K. pneumoniae were classified into IncF plasmids. IncX3 single-replicon plasmids (46-57 kb) carried genes encoding relaxases of the MOB_P family, T4CP genes of the VirD4/TraG subfamily, and VirB-like T4SS gene clusters, which were mainly geographically distributed in China. We found 10 bla _NDM-harboring IncN plasmids (38.38-63.05 kb) carrying the NW-type origin of transfer (oriT) regions, genes coding for relaxases of MOB_F family, genes encoding T4CPs of the TrwB/TraD subfamily, and Trw-like T4SS gene clusters, which were also mainly geographically distributed in China. Moreover, we identified 21 IncC plasmids carrying bla _NDM-1 (140.1-329.2 kb), containing the A/C-type oriTs, genes encoding relaxases of MOB_H family, genes encoding T4CPs belonging to TrwB/TraD subfamily, and Tra_F-like T4SS gene clusters. The bla _NDM-harboring IncC plasmids were widely geographically distributed all over the world, mainly in the United States, China and Viet Nam. These findings enhance our understanding of the diversity of bla _NDM-harboring plasmids in K. pneumoniae.

Keywords: Klebsiella pneumoniae; blaNDM; conjugative transfer region; plasmid; replicon types.