Nine different GBS serotypes have been identified and are grouped based on antigenic differences in the structure of the capsule polysaccharide. Three of the nine GBS capsular serotypes have been linked to a majority of neonatal GBS related meningitis. Other GBS virulence factors have been shown to contribute to experimental meningitis including the ��-hemolysin/cytolysin, which is required for proper anchoring of lipoteichoic acid to the cell wall, HvgA and surface proteins that promote interaction with extracellular matrix components such as serine rich repeat protein, fibronectin binding protein, SfbA and the pilus tip adhesin, PilA. The development of neonatal GBS disease begins when the bacteria successfully colonize the vaginal epithelium of a pregnant mother. This involved multiple steps before and after birth, which includes bacterial penetration of the placental membranes or in halation of infected fluids containing GBS. Bacterial meningitis occurs when GBS leaves the bloodstream, breaches the endothelial AR-42 blood-brain barrier and replicates within cerebral spinal fluid, provoking an overwhelming host inflammatory response. The BBB is primarily composed of a single layer of specialized brain microvascular endothelial cells, and together with astrocytes, pericytes, neurons and the extracellular matrix, constitute the neurovascular unit. The BBB functions to protect the brain from circulating toxins and microbial infection by maintaining extremely tight intercellular junctions that comprise gap, adhere desmosomal junctions that link cells together and prohibit pinocytosis. GBS penetration of the BBB involves a complex inter play between the GBS cell surface components and the endothelial cells of the BBB, however, the mechanism by which GBS crosses the BBB and engages the NVU are not well understood. Astrocytes encircle BMEC with their pseudopodia and maintain CEP-18770 direct contact with cerebrospinal capillaries. Several studies indicate that astrocytes up-regulate and maintain BBB functions and are predicted to have an essential role in protection against invasion by GBS and other microbes.