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Mobilization of the nonconjugative virulence plasmid from hypervirulent Klebsiella pneumoniae

Yanping Xu1, Jianfeng Zhang2, Meng Wang2

  • 1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, 200025, China.

Genome Medicine
|July 23, 2021
PubMed
Abstract

Insights

The virulence plasmid of hypervirulent Klebsiella pneumoniae (hvKP) can transfer to carbapenem-resistant K. pneumoniae (CRKP) with the help of conjugative IncF plasmids. This explains how dangerous hybrid strains emerge, posing a significant public health threat.

Area of Science:

  • Microbiology
  • Genetics
  • Public Health

Background:

  • Klebsiella pneumoniae is a global priority pathogen known for acquiring mobile genetic elements carrying resistance and virulence genes.
  • The virulence plasmid of hypervirulent K. pneumoniae (hvKP), previously considered nonconjugative, has spread to carbapenem-resistant K. pneumoniae (CRKP), creating significant public health challenges.
  • The mechanism of virulence plasmid transfer from hvKP to CRKP remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which nonconjugative virulence plasmids are mobilized from hvKP strains into CRKP strains.
  • To investigate the role of conjugative plasmids, specifically IncF plasmids, in this mobilization process.
  • To understand the implications for the emergence of hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP).

Main Methods:

  • Conjugation assays using ST11 CRKP strains as recipients and hvKP strains as donors.
  • Confirmation of transconjugants using pulsed-field gel electrophoresis, PCR, and whole-genome sequencing.
  • In silico analysis of 2608 plasmids from K. pneumoniae strains to assess the distribution of helper and mobilizable plasmids.

Main Results:

  • A nonconjugative virulence plasmid was mobilized into ST11 CRKP strains by conjugative IncF plasmids, under specific conditions or via intermediate E. coli strains.
  • Mobilization occurred through four distinct modes: transfer alone, cotransfer, hybrid plasmid formation, or homologous recombination.
  • A high percentage of identified helper and virulence plasmids contained specific 28-bp fusion sites crucial for mobilization, and all virulence plasmids possessed an origin of transfer site.

Conclusions:

  • Nonconjugative virulence plasmids in ST11 CRKP strains are likely mobilized from hvKP or E. coli intermediates with assistance from conjugative IncF plasmids.
  • These findings highlight the critical role of IncF plasmids in the dissemination of virulence factors.
  • Increased public awareness regarding the rapid spread of virulence plasmids and the emergence of hv-CRKP strains is crucial.
Keywords:
ConjugationIncF plasmidKlebsiella pneumoniaeMobilizationVirulence plasmid

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