Streptococcus pneumoniae utilizes a novel dynamin independent pathway for entry and persistence in brain endothelium

•S. pneumoniae invades brain endothelium through a novel dynamin independent endocytosis pathway.•Invasion through dynamin independent pathway is aided by SPN adhesin and host receptor interaction.•Entry through dynamin independent route promotes enhanced intracellular persistence. Adoption of an endocytosis route promoting safe intracellular trafficking is a pre-requisite for development of invasive diseases by Streptococcus pneumoniae (SPN). We aim to explore the contribution of various endocytic routes in internalization and survival of SPN in blood brain barrier (BBB), a key event in development of pneumococcal meningitis. Pneumococcal entry and survival in brain endothelial cells were evaluated following treatment with combinations of inhibitors to block multiple endocytosis pathways leaving a single entry port open. Entry of SPN into brain endothelium through a novel dynamin independent pathway dictates a separate downstream trafficking itinerary. This allows SPN to evade lysosomal degradation, potentially promoting safe transit across BBB, leading to development of meningitis. [Display omitted]