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

Kin Ki Jim, Rieza Aprianto, Rutger Koning, Arnau Domenech, Jun Kurushima, Diederik van de Beek, Christina M J E Vandenbroucke-Grauls, Wilbert Bitter, Jan-Willem Veening

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)


Pneumolysin is a major virulence factor of Streptococcus pneumoniae that plays a key role in interaction 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 pathways known to be activated by pneumolysin and discover the importance of necroptosis for host survival. Inhibition of this pathway using the drug GSK′872 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.
Original languageEnglish
Article number111851
Pages (from-to)1-22
Number of pages22
JournalCell reports
Issue number12
Publication statusPublished - 20 Dec 2022


  • CP: Immunology
  • CP: Microbiology
  • Danio rerio
  • Streptococcus pneumoniae
  • competence
  • dual RNA-seq
  • host-pathogen interaction
  • meningitis
  • necroptosis

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