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Most studies on how bacteria cross the blood\u2013brain barrier have been performed in vitro using cultured endothelial cells, due to a paucity of animal models. Group B\n                    <jats:italic>Streptococcus<\/jats:italic>\n                    (GBS) is the leading cause of bacterial meningitis in neonates and is primarily thought to cross the blood\u2013brain barrier by transcytosis through endothelial cells. To test this hypothesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    , 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\u2013brain 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\n                    <jats:italic>in vitro<\/jats:italic>\n                    , was found dispensable\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Instead, pro-inflammatory mediators associated with endothelial cell damage and blood\u2013brain barrier breakdown were specifically upregulated in the zebrafish head upon GBS entry into the brain. Therefore, GBS crosses the blood\u2013brain barrier\n                    <jats:italic>in vivo<\/jats:italic>\n                    not by transcytosis, but by endothelial cell lysis and death. Given that we observe the same invasion route for a meningitis-associated strain of\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    , our findings suggest that streptococcal infection of brain blood vessels triggers endothelial cell inflammation and lysis, thereby facilitating brain invasion.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003236","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T16:01:37Z","timestamp":1751558497000},"page":"e3003236","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Group B Streptococci lyse endothelial cells to infect the brain in a zebrafish meningitis model"],"prefix":"10.1371","volume":"23","author":[{"given":"Sumedha","family":"Ravishankar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha 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