{"doi":"10.1371/journal.pbio.3003236","title":"Group B Streptococci lyse endothelial cells to infect the brain in a zebrafish meningitis model","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.","journal":"PLoS Biology","year":2025,"id":521558,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1392394,"name":"Samantha M. Tuohey","orcid":null,"position":1,"is_corresponding":false},{"id":1392395,"name":"Nicole O. Ramos","orcid":null,"position":2,"is_corresponding":false},{"id":328105,"name":"Satoshi Uchiyama","orcid":"0000-0002-0979-7998","position":3,"is_corresponding":false},{"id":1392396,"name":"Megan Hayes","orcid":null,"position":4,"is_corresponding":false},{"id":1248814,"name":"Kalisa Kang","orcid":"0009-0006-1939-8129","position":5,"is_corresponding":false},{"id":225262,"name":"Victor Nizet","orcid":"0000-0003-3847-0422","position":6,"is_corresponding":false},{"id":695523,"name":"Cressida A. Madigan","orcid":"0000-0003-3270-7142","position":7,"is_corresponding":false},{"id":347640,"name":"Sumedha Ravishankar","orcid":"0000-0002-4026-0742","position":0,"is_corresponding":true}],"reference_count":111,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40609050","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}