Neuronal death in pneumococcal meningitis is triggered by pneumolysin and RrgA interactions with β-actin

Neuronal damage is a major consequence of bacterial meningitis, but little known about mechanisms interaction with neurons leading to neuronal cell death. Streptococcus pneumoniae (pneumococcus) cause meningitis and many survivors develop neurological sequelae after the acute infection has resolved, possibly due damage. Here, we studied for pneumococcal interactions neurons. Using human primary neurons, pull-down experiments mass spectrometry, show that pneumococci interact cytoskeleton protein β-actin through pilus-1 adhesin RrgA cytotoxin pneumolysin (Ply), thereby promoting adhesion invasion our bacteremia-derived mouse model, observe RrgA- Ply-expressing co-localize β-actin. purified proteins, Ply, its cholesterol-binding domain 4, interacts plasma membrane, increasing exposure on outer surface filaments, more binding sites available binding, thus enhanced Pneumococcal promotes death increased intracellular Ca 2+ levels depending presence as well actin disassembly. STED super-resolution microscopy showed disruption filaments in infected expressing Ply. Finally, caused by could be inhibited using antibodies against The generated data potentially helps explaining why frequently sequelae.