Formation of a novel multiresistance plasmid co-carrying tigecycline, carbapenem, and other resistance genes by recombination during conjugative transfer in Klebsiella pneumoniae

Abstract

Objective

Klebsiella pneumoniae is a major global nosocomial pathogen, and strains acquiring extended-spectrum β-lactamase (ESBL) or carbapenemase resistance genes exhibit extensive clinical drug resistance, posing a serious public health threat. This study aimed to characterize the genetic features and transferability of resistance determinants in a clinically isolated multidrug-resistant K. pneumoniae strain.

Methods

A multidrug-resistant K. pneumoniae strain was isolated from clinical samples. Whole-genome sequencing was performed to identify the resistance genes carried by the strain and the transposase sequences within the genetic environment of the target resistance genes. Conjugative transfer experiments were conducted to verify the transferability of the identified resistance genes and their genetic recombination characteristics.

Results

The clinical isolate was confirmed to co-carry a tet(A) variant, tmexCD2-toprJ2, and bla_NDM-1 resistance genes. Whole-genome sequencing revealed the presence of IS26, IS3000, and ∆tnpA transposase sequences in the genetic environment of tet(A)v and bla_NDM-1 genes. Conjugative transfer experiments verified the transferability of the different resistance genes, and notably, recombination and co-transfer events of tet(A)v and bla_NDM-1 genes were detected within the conjugative plasmid of the strain.

Conclusions

Transposases play a crucial role in the formation of complex multidrug-resistant K. pneumoniae strains. The findings of this study provide a novel perspective and critical evidence for elucidating the antimicrobial resistance mechanisms and dissemination pathways of multidrug-resistant K. pneumoniae.