{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:49:59Z","timestamp":1785822599018,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Bacterial meningitis is defined as serious inflammation of the central nervous system (CNS) in which bacteria infect the blood\u2013brain barrier (BBB), a network of highly specialized brain endothelial cells (BECs). Dysfunction of the BBB is a hallmark of bacterial meningitis. Group B Streptococcus (GBS) is one of the leading organisms that cause bacterial meningitis, especially in neonates. Macropinocytosis is an actin-dependent form of endocytosis that is also tightly regulated at the BBB. Previous studies have shown that inhibition of actin-dependent processes decreases bacterial invasion, suggesting that pathogens can utilize macropinocytotic pathways for invasion. The purpose of this project is to study the factors that lead to dysfunction of the BBB. We demonstrate that infection with GBS increases rates of endocytosis in BECs. We identified a potential pathway, PLC-PKC-Nox2, in BECs that contributes to macropinocytosis regulation. Here we demonstrate that downstream inhibition of PLC, PKC, or Nox2 significantly blocks GBS invasion of BECs. Additionally, we show that pharmacological activation of PKC can turn on macropinocytosis and increase bacterial invasion of nonpathogenic yet genetically similar Lactococcus lactis. Our results suggest that GBS activates BEC signaling pathways that increase rates of macropinocytosis and subsequently the invasion of GBS.<\/jats:p>","DOI":"10.3390\/pathogens11040474","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T01:03:01Z","timestamp":1650330181000},"page":"474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Group B Streptococcus-Induced Macropinocytosis Contributes to Bacterial Invasion of Brain Endothelial Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2038-9749","authenticated-orcid":false,"given":"Eric R.","family":"Espinal","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teralan","family":"Matthews","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna M.","family":"Holder","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia B.","family":"Bee","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle M.","family":"Humber","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline E.","family":"Brook","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Divyapicigil","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerod","family":"Sharp","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Alabama, 300 Hackberry Lane, Tuscaloosa, AL 35405, USA"},{"name":"Department of Microbiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Center for Convergent Biosciences and Medicine, University of Alabama, Tuscaloosa, AL 35487, USA"},{"name":"Alabama Life Research Institute, University of Alabama, Tuscaloosa, AL 35487, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/S1474-4422(18)30387-9","article-title":"Global, regional, and national burden of meningitis, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"17","author":"Zunt","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jinf.2016.04.009","article-title":"Neurological sequelae of bacterial meningitis","volume":"73","author":"Lucas","year":"2016","journal-title":"J. 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