Biomedical research institute
     
    You are here: Home / Departments / Infection, Immunity and Inflammation / Team C. Poyart, A. Fouet / Molecular bases of GAS tissue colonization

    Molecular bases of GAS tissue colonization

    •  

    Principal Investigator

    Agnès Fouet

    agnes.fouet@inserm.fr 01 40 51 64 50

     

    Objective

    GAS causes a variety of diseases, from non-invasive to invasive infections and post-streptococcal sequelae. GAS, a genetically very diverse bacterium, displays multiple tissue tropisms. An increase of puerperal fever has been reported and currently over 75 000 pregnant women die each year from puerperal infections worldwide, the most severe cases being linked to the presence of GAS. To establish an infection, GAS must first adhere to and multiply at a tissue surface and then invade it. The mechanisms involved remain poorly understood. Our objective is to describe at the molecular and cellular levels the bacterial – host interaction at the onset of a GAS invasive infection with, as a model, GAS decidual infection.

     

    The group

    Agnès Fouet, Scientist; C. Poyart, professor-hospital practitioner; Clara Lambert, PhD fellow; Céline Plainvert, hospital practitioner; Marine Gaillard, engineer.

     

    Research interests

    With the goal of deciphering cellular and molecular mechanisms involved in GAS invasive infections, we set up a relevant and coherent model, matching the prokaryotic and eukaryotic partners. Our research is organized in four axes.

    1)  GAS strains are genetically very diverse, mobile genetic elements composing up to 15% of the genome. One group, the emm28, is associated with endomitritis. We choose, based on genetic and phenotypic criteria, a representative strain among 50 endometritis-eliciting clinical isolates (3).

    2)  The R28 protein is to an emm28-specific adhesin. Through biochemical, genetic and cell biology approaches, we determined that the N-terminal domain mediates the adhesion to host cells including endometrial epithelial and stromal decidual cells. We also characterized R28 cell receptors and demonstrated a direct binding between the R28 N-terminal domain and integrins (1).

    3)  We have set-up an ex vivo model of decidual infection and through its use we are characterizing the role of given GAS virulence factors during the initial steps of tissue colonization. We will determine the host response, cytokine, chemokine and anti- microbial peptide production as well as immune cell recruitment.

    4)  GAS multiplies actively in the presence of cells or tissue. We will identify the molecules produced by the cells that promote bacterial growth and define the bacterial metabolic pathways induced by the cell-secreted molecules.

     

    Main publications and patents

    1. Weckel A, Ahamada D, Bellais S, Méhats C, Plainvert C, Longo M, Poyart C, Fouet A. The N-terminal domain of the R28 protein promotes emm28 Group A Streptococcus adhesion to host cells via direct binding to three integrins. J Biol Chem. (2018) 293:16006-16018. (https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/30150299)
    2. Plainvert C, Longo M, Seringe E, Saintpierre B, Sauvage E, Ma L, Beghain J, Dmytruk N, Collobert G, Hernandez E, Manuel C, Astagneau P, Glaser P, Ariey F, Poyart C, Fouet A. A clone of the emergent Streptococcus pyogenes emm89 clade responsible for a large outbreak in a post-surgery oncology unit in France. Med Microbiol Immunol. (2018). (https://www-ncbi-nlm-nih-gov.gate2.inist.fr/pubmed/29936564)
    3. Longo M., M. De Jode, C. Plainvert, A. Weckel, A. Hua, A. Château, P. Glaser, C. Poyart, A. Fouet. 2015 Complete Genome Sequence of Streptococcus pyogenes emm28 clinical isolate M28PF1, responsible of a puerperal fever. Genome Announ. 3:e00750-15 (http://www.ncbi.nlm.nih.gov.gate2.inist.fr/pubmed/26184934)

     

     

    Financial supports

    These programs are supported by

    Institut National de Veille Sanitaire

    Assistance publique Hôpitaux de Paris (AP-HP),

    DHU Risques et Grossesse

    DIM Malinf One health

    Departments