Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption

Area of Science:

• Neuroscience
• Microbiology
• Pathogen Biology

Background:

• Bacterial meningitis is a leading cause of death and disability globally.
• The mechanisms by which bacterial pathogens breach the blood-central nervous system (CNS) barriers are not fully understood.
• Understanding these mechanisms is crucial for developing effective treatments.

Purpose of the Study:

• To investigate how Streptococcus suis crosses the blood-CNS barriers.
• To identify bacterial factors and host pathways involved in pathogen entry into the brain.
• To explore potential general mechanisms of bacterial virulence.

Main Methods:

• Utilized monolayer translocation assays with human cerebrovascular endothelium.
• Employed diverse inhibitors and agonists to probe signaling pathways.
• Investigated the role of Streptococcus suis surface enzyme adenosine (Ssads) and its orthologs.

Main Results:

• Adenosine from Streptococcus suis Ssads facilitates pathogen entry into mouse brains.
• Activation of host A1 adenosine receptor signaling and cytoskeleton remodeling promote bacterial penetration.
• Ssads orthologs from other bacteria also promote translocation across barriers.

Conclusions:

• Streptococcus suis exploits host A1 adenosine receptor signaling for brain entry.
• Cytoskeleton remodeling is a key host response facilitating bacterial invasion.
• A1 adenosine receptor signaling may represent a general virulence mechanism for various bacterial pathogens.