{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T04:40:03Z","timestamp":1784349603672,"version":"3.55.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R15NS131921"],"award-info":[{"award-number":["R15NS131921"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2024,6,20]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Bacterial meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when bacteria are able to cross the blood\u2013brain barrier (BBB) or the meningeal\u2013cerebrospinal fluid barrier (mBCSFB). The BBB and mBCSFB comprise highly specialized brain endothelial cells (BECs) that typically restrict pathogen entry. Group B\n Streptococcus<\/jats:italic>\n (GBS or\n Streptococcus agalactiae<\/jats:italic>\n ) is the leading cause of neonatal meningitis. Until recently, identification of GBS virulence factors has relied on genetic screening approaches. Instead, we here conducted RNA-seq analysis on GBS when interacting with induced pluripotent stem cell-derived BECs (iBECs) to pinpoint virulence-associated genes. Of the 2,068 annotated protein-coding genes of GBS, 430 transcripts displayed significant changes in expression after interacting with BECs. Notably, we found that the majority of differentially expressed GBS transcripts were downregulated (360 genes) during infection of iBECs. Interestingly,\n codY<\/jats:italic>\n , encoding a pleiotropic transcriptional repressor in low-G + C Gram-positive bacteria, was identified as being highly downregulated. We conducted qPCR to confirm the\n codY<\/jats:italic>\n downregulation observed via RNA-seq during the GBS\u2013iBEC interaction and obtained\n codY<\/jats:italic>\n mutants in three different GBS background parental strains. As anticipated from the RNA-seq results, the\n \n \n \n \n \u2206<\/mml:mo>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n codY<\/jats:italic>\n strains were more adherent and invasive in two\n in vitro<\/jats:italic>\n BEC models. Together, this demonstrates the utility of RNA-seq during the BEC interaction to identify GBS virulence modulators.\n <\/jats:p>\n <\/jats:sec>\n \n IMPORTANCE<\/jats:title>\n \n Group B\n Streptococcus<\/jats:italic>\n (GBS) meningitis remains the leading cause of neonatal meningitis. Research work has identified surface factors and two-component systems that contribute to GBS disruption of the blood\u2013brain barrier (BBB). These discoveries often relied on genetic screening approaches. Here, we provide transcriptomic data describing how GBS changes its transcriptome when interacting with brain endothelial cells. Additionally, we have phenotypically validated these data by obtaining mutants of a select regulator that is highly down-regulated during infection and testing on our BBB model. This work provides the research field with a validated data set that can provide an insight into potential pathways that GBS requires to interact with the BBB and open the door to new discoveries.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/jb.00087-24","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T13:01:02Z","timestamp":1716296462000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Group B\n Streptococcus<\/i>\n transcriptome when interacting with brain endothelial cells"],"prefix":"10.1128","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-4410","authenticated-orcid":false,"given":"Nadine","family":"Vollmuth","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey 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