Virulence attenuation in ST11-K64 <i>Klebsiella pneumoniae</i> explains its divergent clinical manifestation from ST23-K1.
ST11-K64 Klebsiella pneumoniae shows reduced lethality and impaired ability to cause severe infections compared to ST23-K1, indicating different clinical implications for these strains.
Where it sits
this study against the rest of the kisspeptin (kp-10) corpusSummary and findings
The study measured the pathogenicity differences between ST11-K64 and ST23-K1 strains of Klebsiella pneumoniae. Among 847 clinical isolates, 157 (18.5%) were identified as hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP). The ST11-K64 clone showed significantly attenuated lethality in mouse models compared to ST23-K1.
Abstract
The clinical threat posed by <i>Klebsiella pneumoniae</i> is dual-faceted, encompassing both hypervirulence and carbapenem resistance. The emergence of hypervirulent carbapenem-resistant <i>K. pneumoniae</i> (hv-CRKP) merges these threats, with the ST11-K64 clone being a dominant and concerning lineage. However, its clinical presentation diverges from the classic hypervirulent <i>Klebsiella pneumoniae</i> (hvKp); hv-CRKP is isolated from respiratory sites but is notably absent from pyogenic liver abscesses. This distinct clinical niche prompted us to investigate the underlying pathogenicity differences. Among 847 clinical <i>Klebsiella pneumoniae</i> isolates, 157 (18.5%) were identified as hv-CRKP. From this hv-CRKP collection, we selected five representative ST11-K64 isolates for downstream phenotypic and mechanistic analyses. Despite its prevalence and multidrug resistance, the ST11-K64 clone exhibited significantly attenuated lethality in mouse models compared to ST23-K1. Crucially, in a murine intestinal colonization model that mimics natural infection, only ST23-K1 successfully colonized the gut, caused bacteremia, and formed liver abscesses. In contrast, ST11-K64 strains showed impaired intestinal colonization and failed to translocate to the liver. Phenotypic profiling showed reduced capsule viscosity and siderophore production in ST11-K64 relative to ST23-K1, accompanied by diminished macrophage and Kupffer cell-associated fitness. RT-qPCR identified higher expression of <i>rmpA</i>, <i>rmpA2</i>, <i>iroB,</i> and <i>iucA</i> in ST23-K1, and isogenic deletion and complementation of <i>rmpA2</i> or <i>iucA</i> in the ST23-K1 background supported their contribution to capsule/siderophore-associated phenotypes and intracellular survival in RAW264.7 macrophages. Together, these results indicate that while ST11-K64 hv-CRKP represents a serious antimicrobial-resistance threat, its invasive pathogenicity is route- and context-dependent and does not fully recapitulate the classic entero-hepatic hypervirulence of ST23-K1.