Clinical evolution of ST11 carbapenem resistant and hypervirulent Klebsiella pneumoniae

Abstract

Carbapenem-resistant and hypervirulent K. pneumoniae (CR-HvKP) strains that have emerged recently have caused infections of extremely high mortality in various countries. In this study, we discovered a conjugative plasmid that encodes carbapenem resistance and hypervirulence in a clinical ST86 K2 CR-HvKP, namely 17ZR-91. The conjugative plasmid (p17ZR-91-Vir-KPC) was formed by fusion of a non-conjugative pLVPK-like plasmid and a conjugative blaKPC-2-bearing plasmid and is present dynamically with two other non-fusion plasmids. Conjugation of p17ZR-91-Vir-KPC to other K. pneumoniae enabled them to rapidly express the carbapenem resistance and hypervirulence phenotypes. More importantly, genome analysis provided direct evidence that p17ZR-91-Vir-KPC could be directly transmitted from K2 CR-HvKP strain, 17ZR-91, to ST11 clinical K. pneumoniae strains to convert them into ST11 CR-HvKP strains, which explains the evolutionary mechanisms of recently emerged ST11 CR-HvKP strains.

Plasmid Fusion and Recombination Events That Occurred during Conjugation of poxtA -Carrying Plasmids in Enterococci

“…Several studies have shown that replicative transposition or homologous recombination played an important role in the evolution of plasmid backbones and the acquisition of antimicrobial resistance genes in Gram-negative bacteria ( 28 , 29 , 31 – 33 ). To the best of our knowledge, this is the first time that the roles of replicative transposition and homologous recombination were shown in the shaping of poxtA -carrying plasmids from mobilizable to conjugative in enterococci, which are important health care-associated Gram-positive opportunistic pathogens.…”

Transmission of pLVPK-like virulence plasmid in Klebsiella pneumoniae mediated by an Incl1 conjugative helper plasmid

“…However, convergence of hypervirulence and antibiotic resistance encoding genetic elements harbored by HvKP and multidrug resistant (MDR) K. pneumoniae strains has occurred, generating highly virulent strains that are also difficult to eliminate during antimicrobial treatments ( Lam et al., 2019 ; Shen et al., 2019 ; Turton et al., 2019 ; Yang et al., 2021 ). Furthermore, hypervirulence-encoding genes have been found to disseminate extensively to MDR Klebsiella strains through various plasmid-mediated conjugation mechanisms ( Li et al., 2020 ; Xie et al., 2021 ). A recent study discovered that the pLVPK-like virulence plasmid could be transferred from HvKP strains to ST11 CRKP and Escherichia coli strains with the help of a self-transferable IncF plasmid in various modes ( Xu et al., 2021 ).…”

Conjugation of a Hybrid Plasmid Encoding Hypervirulence and Carbapenem Resistance in Klebsiella pneumoniae of Sequence Type 592

“…Unfortunately, it remains unknown whether pCRHV-C2244 transferred as a single plasmid or as a fused one with the helper plasmid ( Jin et al, 2021 ). Very recently, it has been found that in a ST86 hvCRKP, a non-conjugative pLVPK-like plasmid could fuse with a conjugative bla KPC–2 -carrying plasmid during conjugation via homologous recombination of a 275-bp short region and therefore realized the conjugative transfer of both plasmids as a single entity ( Xie et al, 2021 ). In literature, it has been demonstrated that recombination can occurred between very short (<100 bp) sequence of homology ( Shen and Huang, 1986 ; Kotani and Kmiec, 1994 ; Yu et al, 2000 ; Ira and Haber, 2002 ; Sagi et al, 2006 ; Jang et al, 2018 ; Lu et al, 2019 ) and for E. coli , as little as 23 bp of sequence homology are adequate for efficient recombination ( Shen and Huang, 1986 ).…”