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    Physiopathogeny of Group B Streptococcus

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    Team leader Claire Poyart

    Principal Investigator Claire Poyart
    claire.poyart@aphp.fr
    01 58 41 15 60

     

    Objective

     Streptococcus agalactiae, Group B Streptococcus, SGB, is a normal component of the digestive flora of numerous mammals and is found in the vaginal flora of 30% women. It is a formidable pathogen for the neonate and is the leading cause of neonatal infections in the industrialized countries. Many worldwide epidemiological studies have identified a capsular type III clone, coined ST-17, as responsible for roughly half the early, 70% of the late onset diseases and two-thirds of the meningitis. Yet, this clone represents only 15% of the adult strains. Our studies aim at understanding this apparent paradox and at deciphering what renders this clone hyper virulent for the neonate.  

     

    The group

    C. Poyart, PU-PH
    Agnès Fouet, Scientist
    Julie Guignot, Scientist
    Asmaa Tazi, MCU-PH
    Constantin Hays, PhD student
    Anne-Sophie Bourrel, AHU.

     

    Research interests

    Neonate infections come forward as either an early onset disease (EOD) or a late onset disease (LOD), occurring during the first week of life or between the first week and three months after birth, respectively. The EOD, characterized by a pneumoniae, results most of the time from the ingestion or inhalation of contaminated vaginal secretions during birth by the neonate. The LOD is characterized by a septicemia with no obvious portal of entry and often associated with meningitis. A transmission during birth is the most plausible scenario suggesting that the bacterium could persist in the newborn digestive tract and in some instances cross the intestinal barrier.

    The ST-17 clone displays two specific surface proteins, HvgA and Srr2. We have assigned the ST-17 clone hypervirulence to enhanced capacities to colonize the intestinal tract and to cross the blood brain barrier (BBB). HvgA favors adhesion to epithelial cells and to micro-vessels endothelial cells, which constitute the BBB. Moreover, HvgA is necessary in vivo for intestinal colonization and translocation through intestinal and BB barriers (ref. 2,3). As for Srr2, in contrast to Srr1, the homologous protein found in non-ST-17 clones, it binds plasminogen and plasmin (ref. 1). Furthermore, Srr2 is strongly expressed and binds fibrinogen with a higher affinity than Srr1. The Srr2 plasmatic protein binding capacity leads to the formation of bacterial aggregates that are efficiently phagocytosed. Moreover, Srr2 increases bacterial survival to phagocytic killing and bacterial persistence in a murine model of bacterial meningitis. Thus, Srr2 is a multifaceted adhesin used by the ST-17 clone to hijack ligands of the host coagulation system, thereby contributing to bacterial dissemination and invasiveness, and ultimately to meningitis.

    Nevertheless, these characteristics do not, on their on, explain the association between the ST-17 clone and neonatal infections. Host factors are certainly involved in its hypervirulence in this context. Our current studies use different cellular and tissue models to identify molecular and cellular mechanisms involved in the crossing of these different barriers.

     

    Main publications and patents

    1. Six A, Bellais S, Bouaboud A, Fouet A, Gabriel C, Tazi A, Dramsi S, Trieu-Cuot P, Poyart C. Srr2, a multifaceted adhesin expressed by ST-17 hypervirulent Group B Streptococcus involved in binding to both fibrinogen and plasminogen. Mol Microbiol. 2015 Sep;97(6):1209-22.
    2. Tazi A, Bellais S, Tardieux I, Dramsi S, Trieu-Cuot P, Poyart C. Group B Streptococcus surface proteins as major determinants for meningeal tropism. Curr Opin Microbiol. 2012 Feb;15(1):44-9.
    3. Tazi A, Disson O, Bellais S, Bouaboud A, Dmytruk N, Dramsi S, Mistou MY, Khun H, Mechler C, Tardieux I, Trieu-Cuot P, Lecuit M, Poyart C. The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates. J Exp Med. 2010 Oct 25;207(11):2313-22.
    4. Firon A, Tazi A, Da Cunha V, Brinster S, Sauvage E, Dramsi S, Golenbock DT, Glaser P, Poyart C, Trieu-Cuot P. The Abi-domain protein Abx1 interacts with the CovS histidine kinase to control virulence gene expression in group B Streptococcus. PLoS Pathog. 2013 Feb;9(2):e1003179.
    5. Dramsi S, Morello E, Poyart C, Trieu-Cuot P Epidemiologically and clinically relevant Group B Streptococcus isolates do not bind collagen but display enhanced binding to human fibrinogen. Microbes Infect. 2012;14(12):1044-8

                          

    Patent

    Brevet 2015 : The immunogenic peptide BR of Srr2 use for diagnostic and therapeutic of the "high-virulent" ST-17 clone of group B Streptococcus. EP15305541 10-04-15 Claire Poyart, Patrick Trieu Cuot, Shaynooor Dramsi, Anne Six, Samuel Bellais

     

    Financial supports

    These programs are supported by
    Fondation pour la Recherche Médicale (Grant N°DEQ20100318279),
    DIM Mal INF
    Institut Pasteur
    Ministère de la Recherche et de l’Enseignement Supérieur University Paris Descartes, Grant N° 641 113 10.