Pneumolysin promotes host cell necroptosis and bacterial competence during pneumococcal meningitis as shown by whole-animal dual RNA-seq

Pneumolysin is a major virulence factor of Streptococcus pneumoniae that plays a key role in interac-tion with the host during invasive disease. How pneumolysin influences these dynamics between host and pathogen interaction during early phase of central nervous system infection in pneumococcal meningitis remains unclear. Using a whole-animal in vivo dual RNA sequencing (RNA-seq) approach, we identify pneumolysin-specific transcriptional responses in both S. pneumoniae and zebrafish (Danio rerio) during early pneumococcal meningitis. By functional enrichment analysis, we identify host path-ways known to be activated by pneumolysin and discover the importance of necroptosis for host sur-vival. Inhibition of this pathway using the drug GSK0872 increases host mortality during pneumococcal meningitis. On the pathogen's side, we show that pneumolysin-dependent competence activation is crucial for intra-host replication and virulence. Altogether, this study provides new insights into pneumolysin-specific transcriptional responses and identifies key pathways involved in pneumococcal meningitis.

Automated summary

This study investigates the specific transcriptional responses of pneumolysin and identifies key pathways involved in early pneumococcal meningitis using an in vivo dual RNA sequencing approach. The study provides new insights into the interactions between the host and pathogen during the early phase of central nervous system infection.