Comparative genomics of carbapenem resistance and virulence associated with respiratory tract and bloodstream infections in carbapenem-resistant Klebsiella pneumoniae
TL;DR
These findings provide a comprehensive genomic characterization of CRKP from respiratory tract and bloodstream infections and support genome-based surveillance integrating clonal lineages, capsular types, and plasmid architectures to strengthen infection control and facilitate early identification of emerging high-risk CRKP lineages.
Abstract
ABSTRACT The convergence of resistance and hypervirulence in Klebsiella pneumoniae poses a severe global health threat, yet the genomic mechanisms underlying adaptation to different clinical source remain incompletely understood. We conducted longitudinal genomic surveillance of 282 carbapenem-resistant K. pneumoniae (CRKP) isolates (225 sputum, 57 blood) between 2021and 2024 to characterize population structure, source-associated genomic adaptations, and plasmid evolution. ST11-CG258 dominated the cohort (77.3%), with 61.3% of isolates exhibiting the CR-hvKP phenotype. Longitudinal analysis revealed significant capsular plasticity within ST11, characterized by a temporal shift from KL64/47 to KL25 and the emergence of the highly invasive ST16-KL51 lineage, whereas non-ST11 clones displayed high capsular fidelity. Although blaKPC-2 predominated, blaOXA-181 was enriched among bloodstream isolates, whereas three blaNDM variants were more frequently detected in respiratory isolates. Comparative genomics identified enrichment of genes assigned to COG categories associated with energy production and amino acid transport in bloodstream isolates, whereas sputum isolates showed enrichment of genes involved in DNA repair and insertion sequences. Plasmid clustering of carbapenem-resistant plasmid revealed six antimicrobial clusters (Aclusters 1–6), identifying hybrid plasmids within Acluster 1 co-carrying blaKPC-2 and essential virulence determinants (iucABCD-iutA, rmpA, peg-344). Hypervirulent plasmids formed two major clusters, with Vcluster 2 diverging from Vcluster 1 via a 40kb deletion encompassing the ter (tellurium resistance) operon and metabolism-associated genes. These findings provide a comprehensive genomic characterization of CRKP from respiratory tract and bloodstream infections and support genome-based surveillance integrating clonal lineages, capsular types, and plasmid architectures to strengthen infection control and facilitate early identification of emerging high-risk CRKP lineages.