biostudies-literatureZhu NNIAID NIH HHSNINDS NIH HHSNational Institutes of Healthe12651https://www.ebi.ac.uk/biostudies/studies/S-EPMC7933950biostudies-literatureUnknown13(3)Group B Streptococcus (GBS) remains the most common Gram-positive bacterium causing neonatal meningitis and GBS meningitis continues to be an important cause of mortality and morbidity. In this study, we showed that GBS penetration into the brain occurred initially in the meningeal and cortex capillaries, and exploits a defined host cell signaling network comprised of S1P₂ , EGFR, and CysLT1. GBS exploitation of such network in penetration of the blood-brain barrier was demonstrated by targeting S1P₂ , EGFR, and CysLT1 using pharmacological inhibition, gene knockout and knockdown cells, and gene knockout animals, as well as interrogation of the network (up- and downstream of each other). More importantly, counteracting such targets as a therapeutic adjunct to antibiotEMBO molecular medicineTherapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR.PMC7933950R01 AI084984NS091102R01 NS091102AI84984AI113273AI126176R21 AI126176R21 AI113273Zhu NHou ZPrakash AMorris AShe WZhang CSik Kim KLiu WfalseTherapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR.Group B Streptococcus (GBS) remains the most common Gram-positive bacterium causing neonatal meningitis and GBS meningitis continues to be an important cause of mortality and morbidity. In this study, we showed that GBS penetration into the brain occurred initially in the meningeal and cortex capillaries, and exploits a defined host cell signaling network comprised of S1P₂ , EGFR, and CysLT1. GBS exploitation of such network in penetration of the blood-brain barrier was demonstrated by targeting S1P₂ , EGFR, and CysLT1 using pharmacological inhibition, gene knockout and knockdown cells, and gene knockout animals, as well as interrogation of the network (up- and downstream of each other). More importantly, counteracting such targets as a therapeutic adjunct to antibiot2021-01-01T00:00:00Z2021 Mar2026-04-16T13:26:39.296Z2021-03-18T08:31:34ZS-EPMC79339503347481810.15252/emmm.202012651