An original model of brain infection identifies B Streptococcus lipoprotein Blr as a ligand exploiting host endocytosis for blood-brain barrier crossing.

Pathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of brain infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. Several mammalian pathogens were able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular Blr, were important for BBB crossing and virulence in Drosophila. Further, we identified LDL receptor LpR2, expressed in the BBB, as a putative receptor for Blr, allowing GBS translocation through endocytosis. Finally, we demonstrated that Blr is required for BBB crossing in a murine model of infection. Our results support the relevance of Drosophila for studying host-pathogen interactions and identify a new mechanism by which pathogens exploit host barriers to generate brain infection.