Abstract

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a new threat to healthcare. In this study, we analyzed nine CR-hvKp isolates of different sequence-types (ST) recovered from patients with nosocomial infections in two hospitals in Saint Petersburg. Whole-genome sequencing showed that eight of them harbored large mosaic plasmids carrying resistance to carbapenems and hypervirulence simultaneously, and four different types of hybrid plasmids were identified. BLAST analysis showed a high identity with two hybrid plasmids originating in the UK and Czech Republic. We demonstrated that hybrid plasmids emerged due to the acquisition of resistance genes by virulent plasmids. Moreover, one of the hybrid plasmids carried a novel New Delhi metallo-beta-lactamase (NDM) variant, differing from NDM-1 by one amino acid substitution (D130N), which did not provide significant evolutionary advantages compared to NDM-1. The discovery of structurally similar plasmids in geographically distant regions suggests that the actual distribution of hybrid plasmids carrying virulence and resistance genes is much wider than expected.

Highlights

  • Klebsiella pneumoniae (Kpn) is one of the leading causative agents of hospital- and community-acquired infections worldwide

  • We described the emergence of Kpn sequence type (ST) 395 and ST147 isolates in an oncology hospital carrying virulence and blaNDM-1 genes simultaneously; we were unable to pinpoint the location of these genes [9]

  • We aimed to describe the emergence of Kpn isolates of different STs (ST15, ST147, ST395, and ST874) with hybrid plasmids co-harboring virulence genes and blaNDM in the hospitals in St

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Summary

Introduction

Klebsiella pneumoniae (Kpn) is one of the leading causative agents of hospital- and community-acquired infections worldwide. Multidrug-resistant (MDR) and hypervirulent (hvKP) genetic lineages, as well as a recently emerging trend toward their convergence, are the greatest dangers associated with Kpn [1]. Among MDR genetic lineages, the greatest threat is associated with resistance to carbapenems due to the production of carbapenemases. There are several evolutionary pathways for the formation of Kpn genetic lineages that demonstrate high virulence and resistance to carbapenems, all of which are associated with horizontal gene transfer. Two of these pathways are related to the acquisition of additional plasmids through MDR or hvKP isolates. The reason for the prevalence of this evolutionary pathway is probably the fact that virulence plasmids like pLVPK are nonconjugative which is confirmed by their predominant distribution within a limited number of genetic lines

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