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 | Cell Rep. 2022 Dec 20;41(12):111851
Summary
Pneumolysin is a major virulence factor produced by Streptococcus pneumoniae and plays an important role in host-pathogen interactions during invasive infection. Its role during the early stages of pneumococcal meningitis, however, has remained unclear.
In this study, the authors used whole-animal in vivo dual RNA sequencing to investigate pneumolysin-dependent transcriptional responses in both S. pneumoniae and zebrafish during early infection.
Functional enrichment analysis identified host pathways known to respond to pneumolysin and revealed an important role for necroptosis in host survival. Inhibition of this pathway with GSK’872 increased host mortality during infection.
On the bacterial side, the authors showed that pneumolysin-driven activation of competence pathways was essential for replication within the host and for full virulence.
Overall, the findings provide new insight into pneumolysin-specific host-pathogen interactions and key pathways involved in pneumococcal meningitis.
Why REscan for this study
To see where and when the bacteria switched on their competence pathway during infection, the authors used a pneumococcal strain carrying a fluorescent SsbB reporter. The RCM2 REscan confocal microscope imaged infected zebrafish larvae, making the reporter signal visible throughout the whole animal. This imaging supported the study’s key finding: that pneumolysin-driven competence is essential for the bacteria to replicate in the host and cause full disease.