PT  - JOURNAL ARTICLE
AU  - Billel Benmimoun
AU  - Florentia Papastefanaki
AU  - Bruno Périchon
AU  - Katerina Segklia
AU  - Nicolas Roby
AU  - Vivi Miriagou
AU  - Christine Schmitt
AU  - Shaynoor Dramsi
AU  - Rebecca Matsas
AU  - Pauline Spéder
TI  - An original model of brain infection identifies the hijacking of host lipoprotein import as a bacterial strategy for blood-brain barrier crossing
AID  - 10.1101/2020.02.28.970376
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.28.970376
4099  - http://biorxiv.org/content/early/2020/04/02/2020.02.28.970376.short
4100  - http://biorxiv.org/content/early/2020/04/02/2020.02.28.970376.full
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.