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Updated: Oct 11, 2025
Neisseria meningitidis Infection of Induced Pluripotent Stem-Cell Derived Brain Endothelial Cells
Published on: July 14, 2020
Streptococcus pneumoniae utilizes a novel dynamin independent pathway for entry and persistence in brain endothelium
Manalee V Surve1, Shruti Apte1, Smita Bhutda1
1Bacterial Pathogenesis Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Abstract:
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.
Insights
Streptococcus pneumoniae uses a unique endocytosis pathway to enter brain endothelial cells, evading degradation and facilitating meningitis development. This pathway is crucial for safe intracellular trafficking across the blood-brain barrier.
Area of Science:
- Microbiology
- Cell Biology
- Neuroscience
Background:
- Invasive diseases caused by Streptococcus pneumoniae (SPN) require endocytosis for intracellular trafficking.
- The blood-brain barrier (BBB) is a critical site for SPN to breach during meningitis development.
Purpose of the Study:
- To investigate the specific endocytic routes used by SPN for internalization into the BBB.
- To determine the role of these pathways in SPN survival and potential transit across the BBB.
Main Methods:
- SPN entry and survival in brain endothelial cells were assessed.
- Inhibitors were used to block multiple endocytosis pathways, isolating specific entry routes.
Main Results:
- SPN utilizes a novel, dynamin-independent pathway for entry into brain endothelium.
- This unique pathway dictates a distinct intracellular trafficking itinerary, distinct from other endocytic routes.
- The identified pathway allows SPN to evade lysosomal degradation.
Conclusions:
- A dynamin-independent endocytosis route facilitates SPN entry and survival in brain endothelial cells.
- This pathway is critical for SPN's ability to traffic safely across the BBB.
- Targeting this specific pathway may offer a strategy to prevent pneumococcal meningitis.
