PUBLICATION
Group B Streptococci lyse endothelial cells to infect the brain in a zebrafish meningitis model
- Authors
- Ravishankar, S., Tuohey, S.M., Ramos, N.O., Uchiyama, S., Hayes, M.I., Kang, K., Nizet, V., Madigan, C.A.
- ID
- ZDB-PUB-250705-4
- Date
- 2025
- Source
- PLoS Biology 23: e3003236e3003236 (Journal)
- Registered Authors
- Madigan, Cressida
- Keywords
- none
- MeSH Terms
-
- Zebrafish/microbiology
- Streptococcus agalactiae*/pathogenicity
- Streptococcus agalactiae*/physiology
- Animals
- Brain*/microbiology
- Brain*/pathology
- Streptococcal Infections*/microbiology
- Streptococcal Infections*/pathology
- Disease Models, Animal
- Blood-Brain Barrier/microbiology
- Blood-Brain Barrier/pathology
- Meningitis, Bacterial*/microbiology
- Meningitis, Bacterial*/pathology
- Endothelial Cells*/microbiology
- Endothelial Cells*/pathology
- PubMed
- 40609050 Full text @ PLoS Biol.
Citation
Ravishankar, S., Tuohey, S.M., Ramos, N.O., Uchiyama, S., Hayes, M.I., Kang, K., Nizet, V., Madigan, C.A. (2025) Group B Streptococci lyse endothelial cells to infect the brain in a zebrafish meningitis model. PLoS Biology. 23:e3003236e3003236.
Abstract
To cause meningitis, bacteria move from the bloodstream to the brain, crossing the endothelial cells of the blood-brain barrier. Most studies on how bacteria cross the blood-brain barrier have been performed in vitro using cultured endothelial cells, due to a paucity of animal models. Group B Streptococcus (GBS) is the leading cause of bacterial meningitis in neonates and is primarily thought to cross the blood-brain barrier by transcytosis through endothelial cells. To test this hypothesis in vivo, we used optically transparent zebrafish larvae. Time-lapse confocal microscopy revealed that GBS forms extracellular microcolonies in brain blood vessels and causes perforation and lysis of blood-brain barrier endothelial cells, which promotes bacterial entry into the brain. Vessels infected with GBS microcolonies were distorted and contained thrombi. Inhibition of clotting worsened brain invasion, suggesting a host-protective role for thrombi. The GBS lysin cylE, implicated in brain invasion in vitro, was found dispensable in vivo. Instead, pro-inflammatory mediators associated with endothelial cell damage and blood-brain barrier breakdown were specifically upregulated in the zebrafish head upon GBS entry into the brain. Therefore, GBS crosses the blood-brain barrier in vivo not by transcytosis, but by endothelial cell lysis and death. Given that we observe the same invasion route for a meningitis-associated strain of Streptococcus pneumoniae, our findings suggest that streptococcal infection of brain blood vessels triggers endothelial cell inflammation and lysis, thereby facilitating brain invasion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping