Target intelligence / Profile preview

Escherichia coli J5 lipopolysaccharide (J5 LPS) (J5 LPS)

Target
J5 LPS
Molecular classification
Lipopolysaccharide, Endotoxin, Glycolipid, Pathogen-associated molecular pattern (PAMP)
01

Overview

Escherichia coli J5 lipopolysaccharide (LPS) is a truncated form of endotoxin produced by the J5 rough mutant (Rc) strain of E. coli O111:B4, which lacks the O-antigenic side chains but retains the conserved core polysaccharide and Lipid A components [1, 2]. This structural conservation across various Gram-negative species made J5 LPS a primary candidate for developing cross-reactive vaccines and antisera intended to provide cross-protection against diverse bacterial infections and sepsis [2, 3]. Biologically, J5 LPS serves as a potent agonist for the Toll-like receptor 4 (TLR4)/MD-2 complex, initiating a signaling cascade that results in the massive release of pro-inflammatory cytokines like TNF-alpha and IL-1 [4]. In clinical contexts, J5 LPS has been the target of several experimental immunotherapies, including monoclonal antibodies like Nebacumab (Centoxin) and Edobacomab, which were designed to bind and neutralize the endotoxin to prevent septic shock [5]. However, many of these therapies failed to demonstrate significant survival benefits in large-scale clinical trials, leading to significant debate regarding the efficacy of targeting circulating endotoxin in the complex environment of human sepsis [5, 6].

Other names
Escherichia coli J5 endotoxinE. coli J5 Rc mutant lipopolysaccharideRough mutant lipopolysaccharideUDP-galactose 4-epimerase deficient E. coli LPS
02

Mechanism of action

Endotoxin neutralization and prevention of TLR4-mediated inflammatory cascade

03

Biological functions

Immune response inductionInflammatory responseTLR4 signaling pathway activationEndotoxicity
04

Disease associations

SepsisSeptic shockGram-negative bacterial infectionEndotoxemia
05

Safety considerations

Therapeutic failure in clinical trialsPotential for exacerbating inflammation if lysis occurs without neutralizationJarisch-Herxheimer-like reactionsDifficulty in timing administration relative to endotoxin peak
06

Interacting drugs

Nebacumab

3 more in the full profile.

07

Biomarkers

Endotoxin activity assay (EAA)ProcalcitoninC-reactive protein (CRP)Interleukin-6 (IL-6)

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