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Updated: Feb 24, 2026
Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells
Published on: July 14, 2020
Traceability and distribution of Neisseria meningitidis DNA in archived post mortem tissue samples from patients with
Berit Sletbakk Brusletto1,2, Bernt Christian Hellerud3, Else Marit Løberg4,2
1Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital HF, Ullevål Hospital, PO Box 4956 Nydalen, 0424 Oslo, Norway.
Background:
The pathophysiology and outcome of meningococcal septic shock is closely associated with the plasma level of N. meningitidis lipopolysaccharides (LPS, endotoxin) and the circulating level of meningococcal DNA. The aim of the present study was to quantify the number of N. meningitidis in different formalin-fixed, paraffin-embedded (FFPE) tissue samples and fresh frozen (FF) tissue samples from patients with systemic meningococcal disease (SMD), to explore the distribution of N. meningitidis in the body.
Methods:
DNA in FFPE and FF tissue samples from heart, lungs, liver, kidneys, spleen and brain from patients with meningococcal shock and controls (lethal pneumococcal infection) stored at variable times, were isolated. The bacterial load of N. meningitidis DNA was analyzed using quantitative real-time PCR (qPCR) and primers for the capsule transport A (ctrA) gene (1 copy per N. meningitidis DNA). The human beta-hemoglobin (HBB) gene was quantified to evaluate effect of the storage times (2-28 years) and storage method in archived tissue.
Results:
N. meningitidis DNA was detected in FFPE and FF tissue samples from heart, lung, liver, kidney, and spleen in all patients with severe shock. In FFPE brain, N. meningitidis DNA was only detected in the patient with the highest concentration of LPS in the blood at admission to hospital. The highest levels of N. meningitidis DNA were found in heart tissue (median value 3.6 × 107 copies N. meningitidis DNA/μg human DNA) and lung tissue (median value 3.1 × 107 copies N. meningitidis DNA/μg human DNA) in all five patients. N. meningitidis DNA was not detectable in any of the tissue samples from two patients with clinical meningitis and the controls (pneumococcal infection). The quantity of HBB declined over time in FFPE tissue stored at room temperature, suggesting degradation of DNA.
Conclusions:
High levels of N. meningitidis DNA were detected in the different tissue samples from meningococcal shock patients, particularly in the heart and lungs suggesting seeding and major proliferation of meningococci in these organs during the development of shock, probably contributing to the multiple organ failure. The age of archived tissue samples appear to have an impact on the amount of quantifiable N. meningitidis DNA.
Insights
Meningococcal septic shock involves high levels of Neisseria meningitidis DNA in heart and lung tissues, indicating bacterial proliferation and contributing to organ failure. DNA quantity in archived samples decreases over time.
Area of Science:
- Microbiology
- Pathology
- Molecular Biology
Background:
- Systemic meningococcal disease (SMD) pathophysiology is linked to Neisseria meningitidis lipopolysaccharides (LPS) and DNA levels.
- Understanding N. meningitidis distribution in tissues is crucial for diagnosing and treating meningococcal septic shock.
Purpose of the Study:
- To quantify N. meningitidis DNA in various formalin-fixed, paraffin-embedded (FFPE) and fresh-frozen (FF) tissue samples from SMD patients.
- To explore the distribution of N. meningitidis within the body during severe meningococcal disease.
Main Methods:
- DNA extraction from FFPE and FF tissues (heart, lungs, liver, kidneys, spleen, brain) of patients and controls.
- Quantitative real-time PCR (qPCR) targeting the ctrA gene to measure N. meningitidis bacterial load.
- Quantification of human beta-hemoglobin (HBB) to assess DNA integrity in relation to storage time and method.
Main Results:
- N. meningitidis DNA was detected in heart, lung, liver, kidney, and spleen tissues of all severe shock patients.
- Highest N. meningitidis DNA levels were observed in heart (3.6 × 10^7 copies/μg DNA) and lung (3.1 × 10^7 copies/μg DNA) tissues.
- DNA was not detectable in brain tissue of most patients, nor in any samples from meningitis patients or controls; HBB levels decreased with FFPE storage time.
Conclusions:
- High N. meningitidis DNA levels in heart and lungs suggest significant bacterial proliferation contributing to organ failure in meningococcal shock.
- The age and storage method of archived tissue samples impact the quantification of N. meningitidis DNA.
