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Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
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Pneumolysin is the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus

G Zysk1, B K Schneider-Wald, J H Hwang

  • 1Department of Medical Microbiology and Virology, University of Duesseldorf, Duesseldorf, Germany. zysk@uni-duesseldorf.de

Infection and Immunity
|February 13, 2001
PubMed

Insights

Streptococcus pneumoniae damages the blood-brain barrier (BBB) primarily through pneumolysin, a toxin that disrupts endothelial cells. This bacterial component is crucial for BBB breach and subsequent meningitis complications.

Area of Science:

  • Neuroscience
  • Microbiology
  • Cell Biology

Background:

  • The blood-brain barrier (BBB) is a critical interface protecting the brain from pathogens.
  • Streptococcus pneumoniae is a leading cause of bacterial meningitis, necessitating understanding its mechanisms of CNS invasion.

Purpose of the Study:

  • To investigate the effects of Streptococcus pneumoniae on the integrity of the blood-brain barrier (BBB) using in vitro models.
  • To identify the specific bacterial components responsible for BBB damage during pneumococcal meningitis.

Main Methods:

  • Utilized an in vitro BBB model with human brain microvascular endothelial cells (HBMEC) and bovine brain microvascular endothelial cells (BBMEC).
  • Compared the effects of viable S. pneumoniae, pneumolysin-deficient mutants, cell wall components, and purified pneumolysin on endothelial cell integrity.
  • Assessed endothelial cell morphology, monolayer electrical resistance, and signaling pathways (caspase, tyrosine kinases).

Main Results:

  • S. pneumoniae caused rapid rounding and detachment of HBMEC and decreased transendothelial electrical resistance in BBMEC.
  • A pneumolysin-deficient S. pneumoniae mutant did not compromise BBB integrity.
  • Purified pneumolysin induced endothelial cell damage similar to viable bacteria, dependent on protein synthesis, caspase, and tyrosine kinase activity.

Conclusions:

  • Pneumolysin is a key virulence factor of Streptococcus pneumoniae responsible for damaging the BBB.
  • Pneumolysin likely facilitates bacterial entry into the central nervous system and contributes to brain edema in pneumococcal meningitis.

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