Decoding hypervirulence in carbapenem-resistant Klebsiella pneumoniae: genomic and phenotypic profiling reveals capsular polysaccharide as a key driver of pathogenicity.

Summary

Across 59 CRKP isolates, 37% were hypervirulent, and infections with hv-CRKP were linked to higher sepsis incidence and mortality. Capsule production and hypermucoviscosity, under rcsA control, emerged as robust discriminators and mechanistic drivers, with a GWAS signal at rbtT supporting chromosomal determinants of hypervirulence over plasmid genes.

Key Findings

• Among 59 CRKP isolates, 37.29% (22/59) met hypervirulent criteria and were associated with higher sepsis incidence (P=0.028) and mortality.
• Capsule production and hypermucoviscosity robustly discriminated hv-CRKP from non-hypervirulent CRKP.
• GWAS implicated an SNP in the rbtT locus; virulence plasmid-associated genes showed no significant association with hypervirulence.
• Transcriptomics identified rcsA-mediated capsule upregulation as a mechanism conferring macrophage phagocytosis resistance and survival; capsule production and rcsA expression were validated as diagnostic biomarkers.

Clinical Implications

Capsule production/hypermucoviscosity and rcsA expression can be integrated into diagnostic workflows to flag truly hypervirulent CRKP, informing empiric therapy, source control urgency, and infection prevention policies.

Limitations

• Modest number of isolates may limit generalizability across regions and lineages
• Murine subcutaneous challenge model may not fully recapitulate human invasive disease contexts

Future Directions

Prospective multicenter validation of capsule/rcsA biomarkers, development of rapid assays, and evaluation across infection sites and clinical outcomes.