Interaction of fibrinogen and muramidase-released protein promotes the development of Streptococcus suis meningitis

Junping Wang1, Decong Kong2, Shengwei Zhang2

  • 1State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences , Beijing, China ; Urumqi Ethnic Cadres' College , Urumqi, China.

Insights

Streptococcus suis meningitis is worsened by the interaction between muramidase-released protein (MRP) and human fibrinogen (hFg). This interaction increases blood-brain barrier permeability and bacterial invasion, leading to severe meningitis.

Area of Science:

  • Microbiology
  • Pathogenesis
  • Neuroscience

Background:

  • Muramidase-released protein (MRP) is a key virulence factor in Streptococcus suis serotype 2.
  • Previous studies indicate MRP binds human fibrinogen (hFg), but its role in S. suis meningitis remains unclear.

Purpose of the Study:

  • To investigate the functional role of the MRP-hFg interaction in the pathogenesis of S. suis meningitis.

Main Methods:

  • Deletion of the mrp gene in S. suis.
  • Assessing bacterial adherence and traversal across human cerebral microvascular endothelial cells (hCMEC/D3).
  • In vitro and in vivo permeability assays of the blood-brain barrier (BBB).
  • Analysis of bacterial loads and histopathology in a mouse meningitis model.
  • Western blot and immunofluorescence to examine the effect on p120-catenin.

Main Results:

  • Deletion of mrp significantly reduced hFg-mediated bacterial adherence and traversal across hCMEC/D3 cells.
  • The MRP-hFg interaction was found to significantly increase BBB permeability.
  • Wild type S. suis exhibited higher brain bacterial loads and more severe meningitis pathology compared to the mrp mutant.
  • The MRP-hFg interaction disrupts the cell adherens junction protein p120-catenin in hCMEC/D3 cells.

Conclusions:

  • The interaction between MRP and hFg is crucial for S. suis meningitis development.
  • MRP facilitates bacterial invasion and BBB disruption, contributing to meningitis severity.

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