{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:27:47Z","timestamp":1790778467859,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01-NS051247"],"award-info":[{"award-number":["R01-NS051247"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Streptococcus agalactiae<\/jats:named-content>\n            (group B\n            <jats:named-content content-type=\"genus-species\">Streptococcus<\/jats:named-content>\n            [GBS]) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immunocompromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite the use of the currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCSs). Here we investigated the contribution of a transcriptional regulator containing a LytTR domain, LtdR, to GBS pathogenesis. Disruption of the\n            <jats:italic>ltdR<\/jats:italic>\n            gene in the GBS chromosome resulted in a significant increase in bacterial invasion into human cerebral microvascular endothelial cells (hCMEC)\n            <jats:italic>in vitro<\/jats:italic>\n            as well as the greater penetration of the blood-brain barrier (BBB) and the development of meningitis\n            <jats:italic>in vivo<\/jats:italic>\n            . Correspondingly, infection of hCMEC with the \u0394\n            <jats:italic>ltdR<\/jats:italic>\n            mutant resulted in increased secretion of the proinflammatory cytokines interleukin-8 (IL-8), CXCL-1, and IL-6. Further, using a mouse model of GBS vaginal colonization, we observed that the \u0394\n            <jats:italic>ltdR<\/jats:italic>\n            mutant was cleared more readily from the vaginal tract and also that infection with the \u0394\n            <jats:italic>ltdR<\/jats:italic>\n            mutant resulted in increased cytokine production from human vaginal epithelial cells. RNA sequencing revealed global transcriptional differences between the \u0394\n            <jats:italic>ltdR<\/jats:italic>\n            mutant and the parental wild-type GBS strain. These results suggest that LtdR regulates many bacterial processes that can influence GBS-host interactions to promote both bacterial persistence and disease progression.\n          <\/jats:p>","DOI":"10.1128\/iai.00822-17","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T09:48:17Z","timestamp":1524476897000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Characterization of a Two-Component System Transcriptional Regulator, LtdR, That Impacts Group B Streptococcal Colonization and Disease"],"prefix":"10.1128","volume":"86","author":[{"given":"Liwen","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"},{"name":"Department of Cell and Molecular Biology, San Diego State University, San Diego, California, 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