Dual-threat ascent of carbapenem-resistant Klebsiella aerogenes: Plasmid-borne resistance-virulence convergence and global kinship.

OBJECTIVES

To investigate the genomic characteristics, antimicrobial resistance, plasmid transferability, and virulence of carbapenem-resistant Klebsiella aerogenes (CRKA) isolates in China and to assess their global phylogenetic relationships.

METHODS

A total of 29 CRKA isolates were collected from three tertiary hospitals in China between 2017 and 2022. Antimicrobial susceptibility testing, S1-PFGE, Southern blotting, conjugation assays, Illumina-Nanopore hybrid sequencing, and virulence assessments in Galleria mellonella larvae and murine models were performed. Comparative genomic and global phylogenetic analyses were also conducted.

RESULTS

The isolates carried multiple carbapenemase genes, including blaKPC-2/-3, blaNDM-1/-5, and the rarely reported blaOXA-181 in K. aerogenes. These resistance determinants were located on plasmid backbones with conserved transposon structures and were co-located with yersiniabactin virulence loci. The plasmids demonstrated high transferability. Several isolates exhibited in vivo virulence, particularly yersiniabactin-positive strains. Global phylogenetic analysis revealed that the isolates were genetically closely related to CRKA isolates from the United States, Japan, and Singapore. In China, the predominant sequence types showed a shift from ST56 to ST4, ST14, and ST93.

CONCLUSIONS

This study provides the first integrated evidence of the convergence of antimicrobial resistance and virulence in CRKA in China. The emergence of transferable blaOXA-181-bearing lineages highlights the urgent need for genome-based surveillance and coordinated global efforts to prevent the intercontinental spread of these dual-threat pathogens.