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Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models

Carlos J Orihuela1, Jafar Mahdavi, Justin Thornton

  • 1Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

The Journal of Clinical Investigation
|May 14, 2009
PubMed

Insights

Common bacteria causing meningitis, like Streptococcus pneumoniae, bind to the laminin receptor (LR) to enter the central nervous system (CNS). Targeting this LR interaction could prevent and treat bacterial meningitis.

Area of Science:

  • Neuroscience
  • Microbiology
  • Immunology

Background:

  • Prions and neurotropic viruses utilize the laminin receptor (LR) for central nervous system (CNS) entry.
  • The mechanism of CNS entry for common bacterial meningitis pathogens remains unknown.
  • Childhood bacterial meningitis is primarily caused by Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.

Purpose of the Study:

  • To investigate the role of the laminin receptor (LR) in the CNS tropism of key bacterial meningitis pathogens.
  • To identify the specific bacterial adhesins and host receptors involved in the initial attachment to the blood-brain barrier (BBB).

Main Methods:

  • Affinity chromatography and co-immunoprecipitation were used to identify receptor-ligand interactions.
  • Retagging and in vivo imaging techniques were employed to visualize bacterial binding.
  • Mutagenesis studies and competitive binding assays were performed to characterize adhesin-receptor interactions.

Main Results:

  • The 37/67-kDa laminin receptor (LR) was identified as a common binding site for S. pneumoniae, N. meningitidis, and H. influenzae on brain endothelial cells.
  • Specific bacterial adhesins were identified: CbpA (S. pneumoniae), PilQ and PorA (N. meningitidis), and OmpP2 (H. influenzae).
  • A conserved binding site within the carboxyl terminus of LR was suggested by competitive binding experiments.

Conclusions:

  • The laminin receptor (LR) serves as a common entry point for major bacterial meningitis pathogens into the CNS.
  • Bacterial adhesins interacting with LR are crucial for initiating BBB colonization.
  • Targeting the bacterial adhesin-LR interaction presents a potential therapeutic strategy for broad-spectrum prevention and treatment of bacterial meningitis.

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