Data · dataset · 2026
Elucidating novel disease mechanisms in sepsis
Listed in ZivaHub and Deakin Research Online and DMU Figshare — shown once because both records carry DOI 10.17034/32639934.v1
Klebsiella pneumoniae, a Gram-negative pathogen, is a significant cause of pneumonia and sepsis, often exhibiting multidrug resistance.
Description
During sepsis, endothelial dysfunction plays a pivotal role in vascular pathology, characterized by either uncontrolled vasodilation due to excessive nitric oxide (NO) production or vasoconstriction in renal, pulmonary, and intestinal microvasculature, leading to hypoperfusion, hypoxia, and tissue necrosis.
This study employs an ex vivo pressure myography model using rat mesenteric small resistance arteries to elucidate the impact of K. pneumoniae on endothelial and vascular function.Results indicate that K. pneumoniae impairs acetylcholine-induced, endothelium-dependent dilation by inhibiting NO production and attenuating endothelium-derived hyperpolarization through the type VI secretion system effector VgrG4. In vitro studies with human microvascular endothelial cells revealed that K. pneumoniae disrupts endothelial nitric oxide synthase (eNOS) activity through a dual mechanism.
Read the rest (3 more)
VgrG4-mediated mitochondrial ROS release that activates PKCβ, which phosphorylates eNOS at its inhibitory site Thr495. The bacterial capsule promotes protein phosphatase 2A accumulation, leading to dephosphorylation of the eNOS stimulatory siteSer1177. Ex vivo application of PKCβ inhibitor (LY-333531) and mitochondrial ROS scavenger (MitoTEMPO) effectively restored endothelium-dependent dilation in infected vessels.
Moreover, K. pneumoniae significantly attenuated vascular smooth muscle contraction in a type VI secretion system-dependent manner, with the capsule inducing relaxation in precontracted arteries.Despite being traditionally classified as an obligate extracellular pathogen, K. pneumoniae was internalized and survived within endothelial cells. Endothelial cells expelled intracellular K. pneumoniae through TLR4 and cAMP/PKA signaling pathways, triggered by detection of bacterial surface antigens, a process counteracted by the type VI secretion system.
Bacteria that remain within the cell are able to multiply in Klebsiella-containing vacuoles.This study reveals an intricate interplay between endothelial cells and K. pneumoniae, where the pathogen impairs endothelium-mediated dilation by inducing endothelial dysfunction, and evades host-mediated expulsion to maintain an intracellular, replicative niche.
Links
Where it is published
- DOI doi.org/10.17034/32639934.v1 ↗
DOI / persistent id · from zivahub uct ac za
Catalogue records · 1
- OAI-PMH record api.figshare.com/v2/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Af… ↗
metadata API · from zivahub uct ac za
Topics
- From keywords
- Earth & Environmental Science · Earth & Environmental Science · Earth & Environmental Science
- Inferred from text
- Disease 75%
Provenance · 3 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| ZivaHub | oai:figshare.com:article/32639934 | 12 d ago | JSON v1 |
| Deakin Research Online | oai:figshare.com:article/32639934 | 12 d ago | JSON v1 |
| DMU Figshare | oai:figshare.com:article/32639934 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| concepts[disease].local:disease:disease | enrichment · zivahub uct ac za | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:earth-environmental | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · dro deakin edu au | connector:dro_deakin_edu_au@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · figshare dmu ac uk | connector:figshare_dmu_ac_uk@1.0.0 | |
| description | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/description |
| license_text | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| publication_date | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| title | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/title |