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Updated: Nov 16, 2025
Intracranial Subarachnoidal Route of Infection for Investigating Roles of Streptococcus suis Biofilms in Meningitis in a Mouse Infection Model
Published on: July 1, 2018
Streptococcus suis serotype 2 enolase interaction with host brain microvascular endothelial cells and RPSA-induced
Hongtao Liu1, Siyu Lei2, Li Jia1
1Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People's Republic of China.
Abstract:
Host proteins interacting with pathogens are receiving more attention as potential therapeutic targets in molecular medicine. Streptococcus suis serotype 2 (SS2) is an important cause of meningitis in both humans and pigs worldwide. SS2 Enolase (Eno) has previously been identified as a virulence factor with a role in altering blood brain barrier (BBB) integrity, but the host cell membrane receptor of Eno and The mechanism(s) involved are unclear. This study identified that SS2 Eno binds to 40S ribosomal protein SA (RPSA) on the surface of porcine brain microvascular endothelial cells leading to activation of intracellular p38/ERK-eIF4E signalling, which promotes intracellular expression of HSPD1 (heat-shock protein family D member 1), and initiation of host-cell apoptosis, and increased BBB permeability facilitating bacterial invasion. This study reveals novel functions for the host-interactional molecules RPSA and HSPD1 in BBB integrity, and provides insight for new therapeutic strategies in meningitis.
Insights
Streptococcus suis serotype 2 enolase binds to host protein RPSA, triggering a signaling cascade that increases blood-brain barrier permeability and promotes meningitis. This discovery offers new therapeutic targets for bacterial meningitis.
Area of Science:
- Molecular Medicine
- Microbiology
- Neuroscience
Background:
- Host-pathogen interactions are key therapeutic targets.
- Streptococcus suis serotype 2 (SS2) causes meningitis in humans and pigs.
- The SS2 enolase (Eno) virulence factor's host receptor and mechanism for altering blood-brain barrier (BBB) integrity are unknown.
Purpose of the Study:
- To identify the host cell membrane receptor for SS2 Eno.
- To elucidate the molecular mechanisms by which SS2 Eno disrupts BBB integrity.
- To explore potential therapeutic strategies for SS2 meningitis.
Main Methods:
- Binding assays to identify SS2 Eno receptor on porcine brain microvascular endothelial cells.
- Western blotting and kinase assays to analyze intracellular signaling pathways (p38/ERK-eIF4E).
- Assessment of heat-shock protein family D member 1 (HSPD1) expression and host-cell apoptosis.
- Evaluation of BBB permeability.
Main Results:
- SS2 Eno binds to 40S ribosomal protein SA (RPSA) on the surface of porcine brain microvascular endothelial cells.
- This interaction activates intracellular p38/ERK-eIF4E signaling.
- Activation promotes HSPD1 expression, initiates host-cell apoptosis, and increases BBB permeability, facilitating bacterial invasion.
- Novel roles for RPSA and HSPD1 in BBB integrity were revealed.
Conclusions:
- SS2 enolase utilizes RPSA as a receptor to disrupt BBB integrity via p38/ERK-eIF4E-HSPD1 signaling.
- This mechanism contributes to Streptococcus suis serotype 2 meningitis pathogenesis.
- RPSA and HSPD1 are identified as novel targets for therapeutic intervention in meningitis.
