Acquisition of Plasmid with Carbapenem-Resistance Gene blaKPC2 in Hypervirulent Klebsiella pneumoniae, Singapore

Emerg Infect Dis. 2020 Mar;26(3):549-559. doi: 10.3201/eid2603.191230.

Abstract

The convergence of carbapenem-resistance and hypervirulence genes in Klebsiella pneumoniae has led to the emergence of highly drug-resistant superbugs capable of causing invasive disease. We analyzed 556 carbapenem-resistant K. pneumoniae isolates from patients in Singapore hospitals during 2010-2015 and discovered 18 isolates from 7 patients also harbored hypervirulence features. All isolates contained a closely related plasmid (pKPC2) harboring blaKPC-2, a K. pneumoniae carbapenemase gene, and had a hypervirulent background of capsular serotypes K1, K2, and K20. In total, 5 of 7 first patient isolates were hypermucoviscous, and 6 were virulent in mice. The pKPC2 was highly transmissible and remarkably stable, maintained in bacteria within a patient with few changes for months in the absence of antimicrobial drug selection pressure. Intrapatient isolates were also able to acquire additional antimicrobial drug resistance genes when inside human bodies. Our results highlight the potential spread of carbapenem-resistant hypervirulent K. pneumoniae in Singapore.

Keywords: Enterobacteriaceae; K1; K2; Klebsiella pneumoniae; Singapore; antimicrobial resistance; bacteria; blaKPC-2; carbapenem resistance; carbapenemase; conjugation; genome analysis; hypermucoviscosity; hypervirulent; multidrug resistance; plasmid; superbug; virulence; whole-genome sequencing.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Carbapenem-Resistant Enterobacteriaceae / drug effects
  • Carbapenem-Resistant Enterobacteriaceae / genetics
  • Carbapenem-Resistant Enterobacteriaceae / isolation & purification*
  • Carbapenem-Resistant Enterobacteriaceae / pathogenicity
  • Female
  • Hospitals
  • Humans
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / epidemiology*
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification*
  • Klebsiella pneumoniae / pathogenicity
  • Mice
  • Mice, Inbred C57BL
  • Plasmids
  • Singapore / epidemiology
  • Virulence

Substances

  • Anti-Bacterial Agents