Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782189390801403904 |
---|---|
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. |
format | Text |
id | pubmed-2964583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT taziasmaa thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT dissonolivier thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT bellaissamuel thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT bouaboudabdelouhab thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT dmytruknicolas thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT dramsishaynoor thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT mistoumichelyves thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT khunhuot thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT mechlercharlotte thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT tardieuxisabelle thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT trieucuotpatrick thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT lecuitmarc thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT poyartclaire thesurfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT taziasmaa surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT dissonolivier surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT bellaissamuel surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT bouaboudabdelouhab surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT dmytruknicolas surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT dramsishaynoor surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT mistoumichelyves surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT khunhuot surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT mechlercharlotte surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT tardieuxisabelle surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT trieucuotpatrick surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT lecuitmarc surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates AT poyartclaire surfaceproteinhvgamediatesgroupbstreptococcushypervirulenceandmeningealtropisminneonates |