KpnK48 clone driving hypervirulent carbapenem-resistant Escherichia coli epidemics: Insights into its evolutionary trajectory similar to Klebsiella pneumoniae.

AIMS

Hypervirulent and carbapenem-resistant pathogens posed a significant and growing threat to global public health. This study focused on the rapid spread of a hypervirulent carbapenem-resistant E. coli (hv-CREC) subclone and its genomic resembles with hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP), driven by recombination impacting both chromosomal and plasmid gene content.

METHODS

A multicenter molecular epidemiological study was conducted on 653 CREC clinical isolates collected across China (2013-2022), integrated with public genomic data. Pangenome-wide and phylogeographical analyses were performed to uncover recombination events, define the epidemic clone, and trace its evolutionary history. Growth advantage and virulence were evaluated through competition assays and Galleria mellonella infection models.

RESULTS

Sequence types (ST) 167, ST410, ST617, and ST361 collectively accounted for 53.8 % (351/653) of the CREC isolates, with ST167 showing a sharp increase in prevalence after 2017. Among these, subclone named KpnK48 emerged as the primary driver of the increase in ST167 CREC prevalence. Traced to a European origin, KpnK48 rapidly expanded globally, particularly in China. The remarkable success of KpnK48 could plausibly be attributed to enhanced survival and virulence, driven by the acquisition of a ∼492 kb recombinant genomic region which mirrored the genomic architecture underlying the hv-CRKP ST11-K64 clone, reflecting a Klebsiella-like evolutionary path. Additionally, plasmid shift in KpnK48 clone from the prevalent NDM-IncX3 plasmid to Klebsiella-common NDM-IncF plasmid expanded its resistance spectrum and virulence gene repertoire, likely further amplifying its pathogenicity and success.

CONCLUSIONS

The KpnK48 subclone combined the features of hypervirulence and carbapenem resistance, bridging genomic traits of E. coli and K. pneumoniae, signifying a broader evolutionary trend with profound global health implications.