Contributors: Institut Cochin (IC UM3 (UMR 8104 / U1016)); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Centre national de Référence des Streptocoques (CNR); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Microorganismes et Barrières de l'Hôte (Equipe avenir); Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur Paris; Biologie des Bactéries Pathogènes à Gram-positif; Institut Pasteur Paris -Centre National de la Recherche Scientifique (CNRS); Histotechnologie et Pathologie; Institut Pasteur Paris; Hôpital Louis Mourier - AP-HP Colombes; Université Paris Descartes - Paris 5 (UPD5); CHU Necker - Enfants Malades AP-HP; Service des Maladies infectieuses et tropicales CHU Necker; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); This work was supported by the Agence Nationale de la Recherche (ANR HyperVirGBS Project; ANR-08-MIE-015), Institut National de la Santé et de la Recherche Médicale, Institut Pasteur, Fondation pour la Recherche Médicale (FRM), Université Paris Descartes, the Institut de Veille Sanitaire, Programme Transversal de Recherche #190. S. Bellais was a recipient of a post-doctoral fellowship from the ANR-08-MIE-015 grant and O. Disson from FRM and Institut National de la Santé et de la Recherche Médicale.; We are grateful to Alexandra Gruss for helpful discussion and critical reading of the manuscript. We thank Pierre-Olivier Couraud for providing HCMEC/D3 cells.; ANR-08-MIEN-0015,HYPERVIRGBS,Rôle de la protéine Gbs2018C dans l'hypervirulence du clone ST-17 du Streptocoque du groupe B(2008)
نبذة مختصرة : International audience ; 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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