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 find that several mammalian pathogens are able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucine-rich Blr, are important for BBB crossing and virulence in Drosophila. Further, we identify (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we show that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results demonstrate the potential of Drosophila for studying BBB crossing by pathogens and identify a new mechanism by which pathogens exploit the machinery of host barriers to generate brain infection.

能够穿过血脑屏障（BBB）的病原体会引起长期的神经后遗症和死亡。了解神经性病原体如何绕过这种强大的生理屏障是设计治疗策略的先决条件。在这里，我们提出了一种创新的果蝇大脑发育感染模型，将全脑外植体与体内全身感染相结合。我们发现，几种哺乳动物病原体能够穿过果蝇BBB，包括B组链球菌（GBS）。在GBS表面成分中，脂蛋白，尤其是富含B亮氨酸的Blr，对于果蝇中的BBB穿越和毒力很重要。。此外，我们确定在BBB中表达的（V）LDL受体LpR2作为Blr的宿主受体，从而允许GBS通过胞吞作用进行易位。最后，我们表明在鼠类感染模型中，Brl是BBB穿越和致病性所必需的。我们的结果证明了果蝇研究病原体穿越血脑屏障的潜力，并确定了病原体利用宿主屏障机制产生脑部感染的新机制。