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bioRxiv · 10.1101/2025.08.01.668200

Connections between Klebsiella pneumoniae Bloodstream Dynamics and Serotype-Independent Capsule Properties

Kinney, E. L.·Stark, D. J.·Khadka, S.·Bain, W.·Mike, L. A.
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Abstract

Klebsiella pneumoniae bacteremia is a significant public health burden with a 26% mortality rate, which increases when the infecting isolate is multi-drug resistant. An important virulence factor of K. pneumoniae is the capsule, the protective polysaccharide coat which surrounds the outer membrane and is made up of individual capsular polysaccharide (CPS) chains. Capsule can differ in abundance, attachment, and length of the individual CPS chains. Long, uniform CPS chains are associated with a high level of mucoidy. Typically, mucoid CPS is produced by the hypervirulent K. pneumoniae (hvKp) pathotype, which is associated with invasive community-acquired infections. In contrast, the classical K. pneumoniae (cKp) pathotype tends to be non-mucoid and is associated with nosocomial infections and multi-drug resistance. There are over 80 serotypes of K. pneumoniae capsule. Capsule swap experiments have begun to reveal the effect of serotype on virulence and immune interactions. Clinically, the K2 capsule serotype is a common serotype associated with neonatal sepsis cases. Both cKp and hvKp can produce K2 capsule, but how K2-encoding cKp and hvKp strains differ in a bloodstream infection remains unknown. To fill this gap in knowledge, we characterized the surface properties of K2 serotype cKp and hvKp bloodstream infection isolates, then tested the fitness of these strains in bloodstream infection-related in vitro and in vivo assays. Understanding how K2 cKp and hvKp strains differ in pathogenic potential provides further insight into how K. pneumoniae capsule properties influence bloodstream infection pathogenesis. IMPORTANCEMany studies have compared the pathogenesis of the two Klebsiella pneumoniae pathotypes, but did not control for differences in capsule serotype. In this study, we control for the K2 capsule serotype in classical and hypervirulent pathotypes. Our studies reveal that despite the two pathotypes exhibiting similar human serum survival, they display different tissue tropism in a murine bloodstream infection model. Additionally, although these pathotypes produce similar amounts of capsule, the hypervirulent strains are significantly more mucoid. Our study has provided more evidence on how capsule characteristics impact K. pneumoniae bacteremia pathogenesis and the importance of capsule serotype.

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Kinney, E. L., Stark, D. J., Khadka, S., Bain, W., Mike, L. A.. 2025-08-01. Connections between Klebsiella pneumoniae Bloodstream Dynamics and Serotype-Independent Capsule Properties. https://doi.org/10.1101/2025.08.01.668200

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