The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates
Asmaa Tazi,Asmaa Tazi,Olivier Disson,Olivier Disson,Samuel Bellais,Samuel Bellais,Abdelouhab Bouaboud,Abdelouhab Bouaboud,Nicolas Dmytruk,Shaynoor Dramsi,Michel-Yves Mistou,Huot Khun,Charlotte Mechler,Isabelle Tardieux,Isabelle Tardieux,Patrick Trieu-Cuot,Marc Lecuit,Marc Lecuit,Marc Lecuit,Claire Poyart +19 more
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Lethal meningitis triggered by the hypervirulent group B streptococcus clone ST-17 is mediated by a novel surface protein called HvgA.Abstract:
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.read more
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Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion
Samantha J. Dando,Alan Mackay-Sim,Robert Norton,Bart J. Currie,James Anthony St John,Jenny Ekberg,Jenny Ekberg,Michael R. Batzloff,Glen C. Ulett,Ifor R. Beacham +9 more
TL;DR: Recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain are focused on, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.
Journal ArticleDOI
Community-acquired bacterial meningitis.
Diederik van de Beek,Matthijs C. Brouwer,Rodrigo Hasbun,Uwe Koedel,Cynthia G. Whitney,Eelco F. M. Wijdicks +5 more
TL;DR: Despite advances in treatment and vaccinations, community-acquired bacterial meningitis remains one of the most important infectious diseases worldwide and the growing emergence of drug resistance as well as shifts in the distribution of serotypes and groups are fuelling further development of new vaccines and treatment strategies.
Journal ArticleDOI
Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015: Multistate Laboratory and Population-Based Surveillance.
Srinivas Nanduri,Susan Petit,Chad Smelser,Mirasol Apostol,Nisha B Alden,Lee H. Harrison,Ruth Lynfield,Paula Snippes Vagnone,Kari Burzlaff,Nancy L Spina,Elizabeth Dufort,William Schaffner,Ann Thomas,Monica M. Farley,Monica M. Farley,Jennifer H. Jain,Tracy Pondo,Lesley McGee,Bernard Beall,Stephanie J. Schrag +19 more
TL;DR: Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.
Journal ArticleDOI
Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline
Violette Da Cunha,Violette Da Cunha,Mark R. Davies,Mark R. Davies,Pierre-Emmanuel Douarre,Pierre-Emmanuel Douarre,Isabelle Rosinski-Chupin,Isabelle Rosinski-Chupin,Immaculada Margarit,Sebastien Spinali,Tim Perkins,Pierre Lechat,Nicolas Dmytruk,Elisabeth Sauvage,Elisabeth Sauvage,Laurence Ma,Benedetta Romi,Magali Tichit,Maria-José Lopez-Sanchez,Maria-José Lopez-Sanchez,Stéphane Descorps-Declère,Erika Souche,Carmen Buchrieser,Carmen Buchrieser,Patrick Trieu-Cuot,Patrick Trieu-Cuot,Ivan Moszer,Dominique Clermont,Domenico Maione,Christiane Bouchier,David J. McMillan,David J. McMillan,Julian Parkhill,John L. Telford,Gordan Dougan,Mark J. Walker,Matthew T. G. Holden,Matthew T. G. Holden,Claire Poyart,Philippe Glaser,Philippe Glaser +40 more
TL;DR: It is proposed that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates.
Journal ArticleDOI
Group B Streptococcal Colonization, Molecular Characteristics, and Epidemiology
TL;DR: The aim of the current review is to shed new light on the latest epidemiological data and clonal distribution of GBS in addition to discussing the most important colonization determinants at a molecular level to prevent invasive GBS disease worldwide.
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Journal ArticleDOI
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TL;DR: The genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans, was generated and Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactic pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
Journal ArticleDOI
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TL;DR: In this article, normal human brain endothelial cells were transduced by lentiviral vectors incorporating human telomerase or SV40 T antigen, and one was selected for expression of normal endothelial markers, including CD31, VE cadherin, and von Willebrand factor.
Journal ArticleDOI
Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005.
Christina R. Phares,Ruth Lynfield,Monica M. Farley,Janet C. Mohle-Boetani,Lee H. Harrison,Susan Petit,Allen S. Craig,William Schaffner,Shelley M. Zansky,Ken Gershman,Karen Stefonek,Bernadette A. Albanese,Elizabeth R. Zell,Anne Schuchat,Stephanie J. Schrag +14 more
TL;DR: In this article, an analysis of active, population-based surveillance in 10 states participating in the Active Bacterial Core surveillance/Emerging Infections Program Network was performed to describe disease trends among populations that might benefit from vaccination and among newborns during a period of evolving prevention strategies.