Search bioRxiv⌕ Search
Home/Archive/bioRxiv

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.
View original source ↗Export metadata ↓

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.

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

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

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗
bioRxiv2026

Beta-lactam enhancement against methicillin-resistant Staphylococcus aureus by cell wall blockade is autolysis-dependent: a butyrolactone derivative as case in point

Methicillin-resistant Staphylococcus aureus (MRSA) is non-susceptible to beta-lactams. Blockade of cell wall biosynthesis is a potential target for beta-lactam enhancement but requires further investigation. A butyrolactone derivative enhanced beta-lactams against MRSA strains by reducing the availability of D-Ala-D-Ala. Unlike D-cycloserine, it did not inhibit D-Ala-D-Ala ligase (Ddl). Nor did it show an additive or synergistic effect when combined with cycloserine, indicating a unique mechanism for blocking cell wall precursor production that does not involve the traditional Lipid II pathway. Notably, beta-lactam potentiation by our chemical or D-cycloserine was highly dependent on the intrinsic autolytic ability of the tested MRSA strains. Strains that resisted lysis upon Triton X-100 exposure showed a minimal increase in beta-lactam susceptibility, whereas highly autolytic strains showed significant changes in their beta-lactam MICs. We have thus identified autolytic ability as the Achilles Heel in the strategy of targeting cell wall biosynthesis for beta-lactam potentiation.

microbiology↗
bioRxiv2026

Rapid and largely reversible shifts in the canine fecal metabolome during dietary change

Diet can rapidly change the fecal metabolome, but less is known about recovery after the original diet is restored. We used untargeted UPLC-MS metabolomics to analyze 72 fecal samples from nine Pumi dogs during an owner-managed switch from dry food to raw food and back to dry food. Diet phase accounted for a large proportion of variation in both ionization modes. More than 13,000 LC-MS features changed at the first sampling point after the switch to raw food, with a similarly large response after return to dry food. Among features significant in both comparisons, more than 99% changed in opposite directions. At the final sampling point, no positive-mode (ESI+) features and only 13 negative-mode (ESI-) features differed from the second dry-food baseline under the same threshold. BARF-associated patterns persisted in analyses excluding individual dogs and in pedigree-adjusted candidate models, although individual feature effects depended on normalization. Putative metabolites from several biochemical classes differed in their response and recovery. The fecal metabolome therefore changed rapidly and returned largely toward baseline, with differences among dogs.

microbiology↗