Global genomic landscape of hypervirulent Klebsiella pneumoniae: hypervirulence biomarkers, mobile virulence elements, and antimicrobial resistance

Abstract Background Hypervirulent Klebsiella pneumoniae (hvKp) is an important cause of invasive infections and has raised increasing concern because of its potential convergence with antimicrobial resistance. However, estimates of hvKp prevalence vary substantially among studies because of heterogeneous genomic definitions. Here, we assessed the global genomic epidemiology of hvKp using a stringent five-biomarker definition and investigated its temporal distribution, antimicrobial resistance profile, and association with additional virulence-associated mobile elements, such as integrative and conjugative elements (ICEs). Methods A comprehensive dataset of 79,746 non-redundant K. pneumoniae genomes retrieved from GenBank was analyzed. The hvKp classification required the simultaneous presence of five plasmid-encoded biomarkers: iroB , iucA , peg-344 , rmpA , and rmpA2 . Bioinformatic tools were utilized to determine sequence types (STs), capsular polysaccharides (KL), genomic islands, and resistome profiles, alongside spatiotemporal statistical analyses. Results The strict definition identified 3,447 hvKp genomes (4.32%). The major hvKp lineages were ST23, ST65, ST11, ST86, and ST412, primarily exhibiting KL1 and KL2 capsules. Temporally, hvKp genomes spanned from 1911 to 2024; however, the relative proportion of hvKp has remained stable in the last decade. Approximately 65% of hvKp genomes lacked acquired antimicrobial resistance genes, whereas 25% exhibited multidrug resistance and 19% carried carbapenemase genes. ICEKp elements carrying yersiniabactin siderophore were identified in 75% of hvKp genomes, predominantly ICEKp10 and ICEKp3, and 67% of ICEKp-positive genomes also carried the colibactin genotoxin locus. Conclusions The prevalence of genomically defined hvKp is strongly influenced by the biomarkers used for classification, with a stringent five-biomarker criterion yielding substantially lower estimates than studies using fewer markers. Our findings further indicate that hvKp is a long-standing and globally distributed pathotype, while its relative prevalence and antimicrobial resistance burden have remained largely stable in the contemporary genomic era. It was noticed a convergence between hvKp and virulence-associated ICEKp elements, highlighting the complex and lineage-specific architecture of virulence in hvKp.