We pursue the bacterial-host interactions that lead to pathogen penetration of the BBB and to probe the chain of events leading to BBB dysfunction during Central Nervous System (CNS) disease.

Overall general key questions include:

• What are the host signaling pathways and bacterial factors that lead to BBB disruption?
• How does GBS invade and traffic through the BBB endothelium and what are the key intracellular host defenses?
• What are the contribution of astrocytes to neuroinflammation and the progression of bacterial meningitis? 

We have identified various bacterial cell surface components such as pili, serine rich repeat (Srr) glycoproteins and a fibronectin binding protein, SfbA, which contribute to BBB interaction and the development of meningitis. These bacterial factors interact with components of the extracellular matrix (ECM) to promote bacterial uptake and inflammation.

We have demonstrated that GBS can enter or “invade” brain endothelium apically and exit the cell on the basolateral side, thereby crossing the BBB transcellularly. We have also observed that GBS infection of brain endothelium results in an overall reduction and disruption of tight junction proteins. This is dependent on the induction of host factor Snail1, a global transcriptional repressor of tight junctions.  Continued studies seek to determine the fate of intracellular GBS and the mechanism Snail1 induction.