Presenter of 1 Presentation
O062 - MOLECULAR MECHANISMS OF NEURONAL DAMAGE CAUSED BY PNEUMOCOCCAL INFECTION (ID 818)
Abstract
Background
Streptococcus pneumoniae (the pneumococcus) is the main etiological cause of bacterial meningitis globally. 50% of survivors suffer from permanent neurological dysfunctions, such as cognitive and motor delay, hearing loss, and psychiatric disorders, due to a neuronal injury caused by the bacterial infection.
Methods
Through cell-culture assays, we have investigated the cytotoxicity inflicted by pneumococci to human neurons, and the capacity of pneumococci to interact (adhesion/invasion) with neurons. In vitro assays using purified proteins were performed to investigate pneumococcal-neuron interaction. Results were confirmed with our in vivo meningitis mouse model combined with ex vivo high-resolution immunofluorescence microscopy analysis.
Results
Thanks to their elasticity and motility, neurons present some cytoskeleton β-actin filaments exposed on their plasma membrane. S. pneumoniae can invade and kill neurons through interaction with the pneumococcal pilus-1 adhesin RrgA and pneumolysin with the neuronal β-actin filaments exposed on the neuronal plasma membrane. S. pneumoniae can then exploit the interaction with neuronal β-actin to invade neurons causing disruption of the cytoskeleton. Importantly, when the surface-exposed β-actin filaments are blocked with specific antibodies, pneumococcal adhesion to neurons is prevented and neurons in vitro survive from pneumococcal infection.
Conclusions
For the first time in literature, our study published in 2021 in PLOS Pathogens has shed light into important aspects of pneumococcal-neuron interactions: 1. Pneumococci adhere to and invade neurons through interaction of the pilus-1 tip-protein RrgA and pneumolysin with β-actin exposed on neuronal plasma membrane 2. Blockade of this interaction can prevent neuronal death during a pneumococcal infection in vitro opening new avenues for new therapeutic approaches.