Chasing the landscape for intrahospital transmission and evolution of hypervirulent carbapenem-resistant Klebsiella pneumoniae

Sci Bull (Beijing). 2023 Dec 15;68(23):3027-3047. doi: 10.1016/j.scib.2023.10.038. Epub 2023 Oct 31.

Abstract

The spread of hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) is a global health concern. Here, we report the intrahospital colonization and spread of Hv-CRKP isolates in a tertiary hospital from 2017 to 2022. Analyses of 90 nonredundant CRKP isolates from 72 patients indicated that Hv-CRKP transferability relies on the dominant ST11-K64 clone. Whole-genome sequencing of 11 representative isolates gave 31 complete plasmid sequences, including 12 KPC-2 resistance carriers and 10 RmpA virulence vehicles. Apart from the binary vehicles, we detected two types of fusion plasmids, favoring the cotransfer of RmpA virulence and KPC-2 resistance. The detection of ancestry/relic plasmids enabled us to establish genetic mechanisms by which rare fusion plasmids form. Unexpectedly, we found a total of five rmpA promoter variants (P9T-P13T) exhibiting distinct activities and varying markedly in their geographic distributions. CRISPR/Cas9 manipulation confirmed that an active PT11-rmpA regulator is a biomarker for the "high-risk" ST11-K64/CRKP clone. These findings suggest clonal spread and clinical evolution of the prevalent ST11-K64/Hv-CRKP clones. Apart from improved public awareness of Hv-CRKP convergence, our findings might benefit the development of surveillance (and/or intervention) strategies for the dominant ST11-K64 lineage of the Hv-CRKP population in healthcare sectors.

Keywords: Carbapenem-resistant Klebsiella pneumoniae; Fusion plasmid; Hypervirulent CRKP; Intrahospital evolution; ST11-K64; rmpA promoter.

MeSH terms

  • Carbapenem-Resistant Enterobacteriaceae* / genetics
  • Carbapenems / pharmacology
  • Humans
  • Klebsiella Infections* / drug therapy
  • Klebsiella pneumoniae / genetics
  • Multilocus Sequence Typing
  • Plasmids / genetics

Substances

  • Carbapenems