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

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 Meningitis01:24

Bacterial Meningitis

Bacterial meningitis is a severe infectious disease involving inflammation of the meninges, the protective membranes surrounding the brain and spinal cord. It occurs when pathogenic bacteria cross the blood–brain barrier and enter the cerebrospinal fluid. Common causative organisms include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, Listeria monocytogenes, and Escherichia coli K1. The exact route of entry varies by pathogen and host condition.Routes of Entry...
Viral Meningitis01:18

Viral Meningitis

Viral meningitis is the most common form of meningitis and is often referred to as aseptic meningitis to indicate the absence of bacterial involvement. It is generally milder than bacterial meningitis, with symptoms including fever, headache, stiff neck, drowsiness, nausea, photophobia, and vomiting. Rarely, more severe manifestations or death may occur. Common causative agents include enteroviruses, particularly coxsackie A and B viruses and echoviruses, all members of the Enterovirus genus...
Amebiasis01:28

Amebiasis

Entamoeba histolytica, a protozoan parasite, is responsible for intestinal and extraintestinal amebiasis. Though a significant proportion of infections remain asymptomatic, approximately 50 million individuals annually are estimated to present with clinical disease, resulting in up to 100,000 deaths globally. The disease burden is disproportionately high in regions with lower socioeconomic status, such as parts of India, Africa, Mexico, and Latin America.Etiology and TransmissionThe infective...
Bacterial Meningitis I: Introduction01:22

Bacterial Meningitis I: Introduction

Bacterial meningitis is a severe, life-threatening inflammation of the meninges, particularly the pia mater and arachnoid mater, affecting the subarachnoid space, ventricles, and cerebrospinal fluid (CSF). If untreated, it can lead to significant neurological complications or death.Causative AgentsCommon pathogens vary with age and immune status. In adults, major organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus agalactiae (group B...
Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
Encephalitis ll: Pathophysiology01:26

Encephalitis ll: Pathophysiology

Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.Autoimmune EncephalitisIn autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can...