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
  • Necroptosis
  • Streptococcus pneumoniae/metabolism
  • Zebrafish/metabolism
  • RNA-Seq
  • Bacterial Proteins/genetics
  • Bacterial Proteins/metabolism
  • Meningitis, Pneumococcal*/genetics
  • Meningitis, Pneumococcal*/metabolism
  • Meningitis, Pneumococcal*/microbiology
  • Animals
(all 10)
PubMed
36543127 Full text @ Cell Rep.
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
Figures
Figure Gallery (6 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
a9
    		Complex
    i114TgTransgenic Insertion
      ibl150TgTransgenic Insertion
        w2
          		Point Mutation
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          No data available
          Fish
          No data available
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GFPEFGGFP
          1 - 2 of 2
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          Mapping
          No data available
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          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.