Dr. Brandon Kim has been awarded a $447K NIH R15 grant to study impairment of the cerebral vasculature during bacterial meningitis. Bacterial meningitis is a serious life-threatening infection of the central nervous system that occurs when bacteria are able to cross the highly specialized cerebral vasculature and enter the brain. The cells that comprise the cerebral vasculature are collectively known as the blood-brain barrier and possess unique properties that ensure proper brain homeostasis while also restricting toxins and pathogens. Group B Streptococcus (GBS), is the leading cause of neonatal meningitis, and often survivors are left with permanent neurological damage. In this proposal, we seek to discover how the unique properties of the blood-brain barrier fail during GBS meningitis. We will focus on two aspects that make the blood-brain barrier unique; 1) the greatly restricted rates of transcytosis and endocytosis at the blood-brain barrier, and 2) the functional multi-drug efflux transporters at the blood-brain barrier. Together these attributes prevent molecules from entering the brain, however, we have found that GBS can disrupt these key features. Our proposal will discover the mechanisms of blood-brain barrier failure that may have far-reaching implications to many other neurological disorders that also exhibit dysfunctional cerebral vasculature.