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The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates

Streptococcus agalactiae (group B streptococcus; GBS) is a normal constituent of the intestinal microflora and the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized b...

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Autores principales: Tazi, Asmaa, Disson, Olivier, Bellais, Samuel, Bouaboud, Abdelouhab, Dmytruk, Nicolas, Dramsi, Shaynoor, Mistou, Michel-Yves, Khun, Huot, Mechler, Charlotte, Tardieux, Isabelle, Trieu-Cuot, Patrick, Lecuit, Marc, Poyart, Claire
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964583/
https://www.ncbi.nlm.nih.gov/pubmed/20956545
http://dx.doi.org/10.1084/jem.20092594
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author Tazi, Asmaa
Disson, Olivier
Bellais, Samuel
Bouaboud, Abdelouhab
Dmytruk, Nicolas
Dramsi, Shaynoor
Mistou, Michel-Yves
Khun, Huot
Mechler, Charlotte
Tardieux, Isabelle
Trieu-Cuot, Patrick
Lecuit, Marc
Poyart, Claire
author_facet Tazi, Asmaa
Disson, Olivier
Bellais, Samuel
Bouaboud, Abdelouhab
Dmytruk, Nicolas
Dramsi, Shaynoor
Mistou, Michel-Yves
Khun, Huot
Mechler, Charlotte
Tardieux, Isabelle
Trieu-Cuot, Patrick
Lecuit, Marc
Poyart, Claire
author_sort Tazi, Asmaa
collection PubMed
description Streptococcus agalactiae (group B streptococcus; GBS) is a normal constituent of the intestinal microflora and the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized by meningitis in infants after the first week of life. The pathophysiology of LOD remains poorly understood, but our epidemiological and histopathological results point to an oral route of infection. Here, we identify a novel ST-17–specific surface-anchored protein that we call hypervirulent GBS adhesin (HvgA), and demonstrate that its expression is required for GBS hypervirulence. GBS strains that express HvgA adhered more efficiently to intestinal epithelial cells, choroid plexus epithelial cells, and microvascular endothelial cells that constitute the blood–brain barrier (BBB), than did strains that do not express HvgA. Heterologous expression of HvgA in nonadhesive bacteria conferred the ability to adhere to intestinal barrier and BBB-constituting cells. In orally inoculated mice, HvgA was required for intestinal colonization and translocation across the intestinal barrier and the BBB, leading to meningitis. In conclusion, HvgA is a critical virulence trait of GBS in the neonatal context and stands as a promising target for the development of novel diagnostic and antibacterial strategies.
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spelling pubmed-29645832011-04-25 The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates Tazi, Asmaa Disson, Olivier Bellais, Samuel Bouaboud, Abdelouhab Dmytruk, Nicolas Dramsi, Shaynoor Mistou, Michel-Yves Khun, Huot Mechler, Charlotte Tardieux, Isabelle Trieu-Cuot, Patrick Lecuit, Marc Poyart, Claire J Exp Med Brief Definitive Report Streptococcus agalactiae (group B streptococcus; GBS) is a normal constituent of the intestinal microflora and the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized by meningitis in infants after the first week of life. The pathophysiology of LOD remains poorly understood, but our epidemiological and histopathological results point to an oral route of infection. Here, we identify a novel ST-17–specific surface-anchored protein that we call hypervirulent GBS adhesin (HvgA), and demonstrate that its expression is required for GBS hypervirulence. GBS strains that express HvgA adhered more efficiently to intestinal epithelial cells, choroid plexus epithelial cells, and microvascular endothelial cells that constitute the blood–brain barrier (BBB), than did strains that do not express HvgA. Heterologous expression of HvgA in nonadhesive bacteria conferred the ability to adhere to intestinal barrier and BBB-constituting cells. In orally inoculated mice, HvgA was required for intestinal colonization and translocation across the intestinal barrier and the BBB, leading to meningitis. In conclusion, HvgA is a critical virulence trait of GBS in the neonatal context and stands as a promising target for the development of novel diagnostic and antibacterial strategies. The Rockefeller University Press 2010-10-25 /pmc/articles/PMC2964583/ /pubmed/20956545 http://dx.doi.org/10.1084/jem.20092594 Text en © 2010 Tazi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Tazi, Asmaa
Disson, Olivier
Bellais, Samuel
Bouaboud, Abdelouhab
Dmytruk, Nicolas
Dramsi, Shaynoor
Mistou, Michel-Yves
Khun, Huot
Mechler, Charlotte
Tardieux, Isabelle
Trieu-Cuot, Patrick
Lecuit, Marc
Poyart, Claire
The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
title The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
title_full The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
title_fullStr The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
title_full_unstemmed The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
title_short The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
title_sort surface protein hvga mediates group b streptococcus hypervirulence and meningeal tropism in neonates
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964583/
https://www.ncbi.nlm.nih.gov/pubmed/20956545
http://dx.doi.org/10.1084/jem.20092594
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