RT Journal Article SR Electronic T1 An original model of brain infection identifies the hijacking of host lipoprotein import as a bacterial strategy for blood-brain barrier crossing JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.28.970376 DO 10.1101/2020.02.28.970376 A1 Billel Benmimoun A1 Florentia Papastefanaki A1 Bruno Périchon A1 Katerina Segklia A1 Nicolas Roby A1 Vivi Miriagou A1 Christine Schmitt A1 Shaynoor Dramsi A1 Rebecca Matsas A1 Pauline Spéder YR 2020 UL http://biorxiv.org/content/early/2020/04/02/2020.02.28.970376.abstract AB Pathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. We identified several mammalian pathogens able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucin-rich Blr, were important for BBB crossing and virulence in Drosophila. Further, we identified (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we demonstrated that Blr is required for BBB crossing and pathogenicity 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.