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.
Abstract:
Muramidase-released protein (MRP) is as an important virulence marker of Streptococcus suis (S. suis) serotype 2. Our previous works have shown that MRP can bind human fibrinogen (hFg); however, the function of this interaction in S. suis meningitis is not known. In this study, we found that the deletion of mrp significantly impairs the hFg-mediated adherence and traversal ability of S. suis across human cerebral microvascular endothelial cells (hCMEC/D3). Measurement of the permeability to Lucifer yellow in vitro and Evans blue extravasation in vivo show that the MRP-hFg interaction significantly increases the permeability of the blood-brain barrier (BBB). In the mouse meningitis model, wild type S. suis caused higher bacterial loads in the brain and more severe histopathological signs of meningitis than the mrp mutant at day 3 post-infection. Western blot analysis and immunofluorescence observations reveal that the MRP-hFg interaction can destroy the cell adherens junction protein p120-catenin of hCMEC/D3. These results indicate that the MRP-hFg interaction is important in the development of S. suis meningitis.
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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