PUBLICATION
Pneumolysin promotes host cell necroptosis and bacterial competence during pneumococcal meningitis as shown by whole-animal dual RNA-seq
- Authors
- Jim, K.K., Aprianto, R., Koning, R., Domenech, A., Kurushima, J., van de Beek, D., Vandenbroucke-Grauls, C.M.J.E., Bitter, W., Veening, J.W.
- ID
- ZDB-PUB-221222-8
- Date
- 2022
- Source
- Cell Reports 41: 111851111851 (Journal)
- Registered Authors
- Bitter, Wilbert
- Keywords
- CP: Immunology, CP: Microbiology, Danio rerio, Streptococcus pneumoniae, competence, dual RNA-seq, host-pathogen interaction, meningitis, necroptosis
- Datasets
- GEO:GSE123988
- MeSH Terms
-
- Animals
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism
- Meningitis, Pneumococcal*/genetics
- Meningitis, Pneumococcal*/metabolism
- Meningitis, Pneumococcal*/microbiology
- Necroptosis
- RNA-Seq
- Streptococcus pneumoniae/metabolism
- Zebrafish/metabolism
- PubMed
- 36543127 Full text @ Cell Rep.
Citation
Jim, K.K., Aprianto, R., Koning, R., Domenech, A., Kurushima, J., van de Beek, D., Vandenbroucke-Grauls, C.M.J.E., Bitter, W., Veening, J.W. (2022) Pneumolysin promotes host cell necroptosis and bacterial competence during pneumococcal meningitis as shown by whole-animal dual RNA-seq. Cell Reports. 41:111851111851.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping