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Updated: Aug 9, 2026

Purification and Visualization of Lipopolysaccharide from Gram-negative Bacteria by Hot Aqueous-phenol Extraction
Published on: May 28, 2012
Neisseria meningitidis lipopolysaccharides in human pathology
P Brandtzaeg1, A Bjerre, R Øvstebø
1Departments of Pediatrics, Ullevål University Hospital, University of Oslo, Oslo, Norway. petter.brandtzaeg@ioks.uio.no
Abstract:
Neisseria meningitidis causes meningitis, fulminant septicemia or mild meningococcemia attacking mainly children and young adults. Lipopolysaccharides (LPS) consist of a symmetrical hexa-acyl lipid A and a short oligosaccharide chain and are classified in 11 immunotypes. Lipid A is the primary toxic component of N. meningitidis. LPS levels in plasma and cerebrospinal fluid as determined by Limulus amebocyte lysate (LAL) assay are quantitatively closely associated with inflammatory mediators, clinical symptoms, and outcome. Patients with persistent septic shock, multiple organ failure, and severe coagulopathy reveal extraordinarily high levels of LPS in plasma. The cytokine production is compartmentalized to either the circulation or to the subarachnoid space. Mortality related to shock increases from 0% to > 80% with a 10-fold increase of plasma LPS from 10 to 100 endotoxin units/ml. Hemorrhagic skin lesions and thrombosis are caused by up-regulation of tissue factor which induces coagulation, and by inhibition of fibrinolysis by plasminogen activator inhibitor 1 (PAI-1). Effective antibiotic treatment results in a rapid decline of plasma LPS (half-life 1-3 h) and cytokines, and reduced generation of thrombin, and PAI-1. Early antibiotic treatment is mandatory. Three intervention trials to block lipid A have not significantly reduced the mortality of meningococcal septicemia.
Insights
Neisseria meningitidis lipopolysaccharides (LPS) are toxic, driving severe septic shock. Early antibiotic treatment rapidly reduces LPS and improves outcomes, though lipid A blockade trials have failed to lower mortality.
Area of Science:
- Microbiology
- Immunology
- Critical Care Medicine
Background:
- Neisseria meningitidis causes severe infections like meningitis and septicemia, primarily in children and young adults.
- Lipopolysaccharides (LPS), particularly the toxic Lipid A component, are key virulence factors.
- LPS levels correlate with disease severity, inflammatory mediators, and patient outcomes.
Purpose of the Study:
- To investigate the role of LPS in meningococcal disease pathogenesis and patient outcomes.
- To assess the impact of LPS levels on clinical manifestations and mortality.
- To evaluate the effectiveness of early antibiotic treatment and potential lipid A-blocking therapies.
Main Methods:
- Quantification of LPS in plasma and cerebrospinal fluid using the Limulus amebocyte lysate (LAL) assay.
- Monitoring of inflammatory mediators, clinical symptoms, and coagulopathy.
- Analysis of treatment effects on LPS, cytokine levels, and coagulation factors.
Main Results:
- High plasma LPS levels are associated with persistent septic shock, organ failure, and coagulopathy.
- Mortality risk significantly increases with elevated plasma LPS concentrations.
- Effective antibiotic treatment leads to rapid LPS clearance and reduced inflammatory markers.
- Hemorrhagic lesions and thrombosis are linked to tissue factor upregulation and PAI-1 inhibition.
Conclusions:
- LPS is a critical determinant of severity and mortality in meningococcal septicemia.
- Early antibiotic intervention is crucial for reducing LPS levels and improving patient survival.
- Targeting Lipid A has not yet proven effective in reducing mortality in clinical trials.
Related Concept Videos
Bacterial Meningitis
Viral Meningitis
Amebiasis
Bacterial Meningitis I: Introduction
Bacterial Meningitis II: Pathophysiology
Encephalitis ll: Pathophysiology

