hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts.

() penetration of the blood-brain barrier (BBB) is the key step essential for the development of meningitis. In a recent paper (Nat Commun 9:2296), we identify Caspr1 as a host receptor for virulence factor IbeA to pave the way the penetration of bacteria through the BBB. Bacterial IbeA interacts with endothelial Caspr1 to trigger intracellular focal adhesion kinase activation, leading to internalization into the brain endothelial cells. Importantly, endothelial knockout of Caspr1 in mice significantly reduced crossing through the BBB. Based on the results that extracellular aa 203-355 of Caspr1 bind with IbeA, we tested the blocking effect of recombinant Caspr1(203-355) peptides in neonatal rat model of meningitis. The results showed that Caspr1(203-355) peptides effectively attenuated penetration into the brain during meningitis, indicating that Caspr1(203-355) peptides could be used to neutralize the virulent IbeA to prevent meningitis. We further found that can directly invade into hippocampal neurons causing apoptosis which required the interaction between bacterial IbeA and neuronal Caspr1. These findings demonstrate that hijack Caspr1 as a host receptor for penetration of BBB and invasion of hippocampal neurons, resulting in progression of meningitis.