Genomic Evolution of the Increasing Prevalent Carbapenem-Resistant Hypervirulent ST15 Klebsiella pneumoniae

ST15 Klebsiella pneumoniae (Kp) is increasingly prevalent in China and worldwide. Currently, the mechanisms underlying the acquisition of hypervirulence-associated genes in sequence Type 15 (ST15) Kp are still not well studied. The global prevalence of ST15 Kp is increasing, alongside notable increases in both resistance and virulence.

In this study, we collected 766 isolates of Kp from a tertiary hospital and 19,060 Kp genomes from the NCBI Assembly database. We analyzed the phylogenetic characteristics and profiles of hypervirulence-associated genes among ST15 genomes, as well as their associations with other sequence types (STs).

We observed that the hypervirulence-associated genes in the ST15 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates were all located on plasmids, indicating the potential for horizontal transfer. Plasmid exchange and recombination are closely linked to transmission patterns in different regions. Notably, in Asia, lineages carrying the virulence plasmid genes iucA and rmpA2 constitute the dominant population, accounting for 49.1% of the regional epidemic strains (with 48.5% lacking hypervirulence-associated genes). The clustering of these isolates and their close genetic relationships suggest that hypervirulent ST15 strains are well adapted and spread rapidly in this region. Two main pathways for the acquisition of virulence plasmids by ST15 CRKP isolates were identified: One involves the recombination of nonvirulence plasmids with the classic virulence plasmid pVir from ST11, and the other involves the direct acquisition of virulence plasmids from other genera. We also found that one ST15 CRKP strain harbors multiple copies of key virulence genes.

Overall, the genetic diversity of hypervirulence-associated genes within ST15 CRKP isolates may enhance the ability to survive and spread globally, offering crucial evidence for clinical strategies aimed at managing this strain.