Molecular characterization of carbapenem-resistant and virulent plasmids in Klebsiella pneumoniae from patients with bloodstream infections in China

Emerg Microbes Infect. 2021 Dec;10(1):700-709. doi: 10.1080/22221751.2021.1906163.

Abstract

Bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are potentially life-threatening and an urgent threat to public health. The present study aims to clarify the characteristics of carbapenemase-encoding and virulent plasmids, and their interactions with the host bacterium. A total of 425 Kp isolates were collected from the blood of BSI patients from nine Chinese hospitals, between 2005 and 2019. Integrated epidemiological and genomic data showed that ST11 and ST307 Kp isolates were associated with nosocomial outbreak and transmission. Comparative analysis of 147 Kp genomes and 39 completely assembled chromosomes revealed extensive interruption of acrR by ISKpn26 in all Kp carbapenemase-2 (KPC-2)-producing ST11 Kp isolates, leading to activation of the AcrAB-Tolc multidrug efflux pump and a subsequent reduction in susceptibility to the last-resort antibiotic tigecycline and six other antibiotics. We described 29 KPC-2 plasmids showing diverse structures, two virulence plasmids in two KPC-2-producing Kp, and two novel multidrug-resistant (MDR)-virulent plasmids. This study revealed a multifactorial impact of KPC-2 plasmid on Kp, which may be associated with nosocomial dissemination of MDR isolates.

Keywords: Bloodstream infection; KPC-2; Klebsiella pneumoniae; carbapenem resistance; genomics.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carbapenems / pharmacology*
  • China / epidemiology
  • Drug Resistance, Bacterial
  • Humans
  • Klebsiella Infections / epidemiology
  • Klebsiella Infections / microbiology*
  • Klebsiella pneumoniae / classification
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / isolation & purification*
  • Klebsiella pneumoniae / pathogenicity
  • Microbial Sensitivity Tests
  • Molecular Epidemiology
  • Moths
  • Phylogeny
  • Sepsis / epidemiology
  • Sepsis / microbiology*
  • Virulence
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • beta-Lactamases
  • carbapenemase

Grant support

This work was funded by the National Natural Science Foundation of China (grant numbers 82061128001, 81722030, 81830103, 81902123), National Key Research and Development Program (grant number 2017ZX10302301), Guangdong Natural Science Foundation (grant number 2017A030306012), Project of high-level health teams of Zhuhai at 2018 (The Innovation Team for Antimicrobial Resistance and Clinical Infection), 111 Project (grant number B12003), Open project of Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education (grant number 2018kfkt01/02), China Postdoctoral Science Foundation (grant number 2019M653192), Science, Technology, and Innovation Commission of Shenzhen Municipality (JCYJ20190807151601699).