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FimH-Mech

The molecular mechanism of E. coli FimH pathogenicity

Total Cost €

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EC-Contrib. €

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Partnership

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Project "FimH-Mech" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 185˙076 €
 EC max contribution 185˙076 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2019-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 185˙076.00

Map

 Project objective

Pathogenic bacteria such as E. coli are responsible for a large variety of diseases, including persistent urinary tract and intestinal infections. Their adhesion to the host cell wall is promoted by the binding of FimH located at the tip of the bacterial fimbriae to highly mannosylated cell surface receptors. To resist human defences such as the urinary flow, bacterial adhesion is enhanced under shear force. The shear-force dependence and thus also the pathogenicity of different E. coli strains has been shown to depend on natural sequential variation of the FimH protein. Also probiotic E. coli strains have been shown to attach to host cells, which raises the question as to why these bacteria evoke a beneficial effect upon their host. The FimH-Mech project intends to decipher the molecular mechanism that determines the pathogenicity of different E. coli strains, by investigating the shear-force dependence of FimH and FimH variants and by modelling the complex formation with one of its targets receptors, namely CEACAM6. The results of these investigations will allow me to establish the molecular difference between a pathogenic and probiotic FimH adhesin. I will use a large variety of state-of-the-art computational and theoretical techniques, such as molecular modelling, quantum mechanics, docking and two-state kinetic models. These techniques will be enriched by but also feed into experimental essays to be performed in the host institute. The thus gained understanding of the molecular action of bacterial adhesins will allow for the development of more efficient inhibitors. This constitutes a promising and important milestone in the design of new non-antibiotic drugs against harmful adhesive bacteria.

 Publications

year authors and title journal last update
List of publications.
2018 Tetiana Dumych, Clarisse Bridot, Sébastien Gouin, Marc Lensink, Solomiya Paryzhak, Sabine Szunerits, Ralf Blossey, Rostyslav Bilyy, Julie Bouckaert, Eva-Maria Krammer
A Novel Integrated Way for Deciphering the Glycan Code for the FimH Lectin
published pages: 2794, ISSN: 1420-3049, DOI: 10.3390/molecules23112794
Molecules 23/11 2019-08-07
2018 Eva-Maria Krammer, Jerome de Ruyck, Goedele Roos, Julie Bouckaert, Marc Lensink
Targeting Dynamical Binding Processes in the Design of Non-Antibiotic Anti-Adhesives by Molecular Simulation—The Example of FimH
published pages: 1641, ISSN: 1420-3049, DOI: 10.3390/molecules23071641
Molecules 23/7 2019-08-07
2017 Mohamed Touaibia, Eva-Maria Krammer, Tze Shiao, Nao Yamakawa, Qingan Wang, Anja Glinschert, Alex Papadopoulos, Leila Mousavifar, Emmanuel Maes, Stefan Oscarson, Gerard Vergoten, Marc Lensink, René Roy, Julie Bouckaert
Sites for Dynamic Protein-Carbohydrate Interactions of O- and C-Linked Mannosides on the E. coli FimH Adhesin
published pages: 1101, ISSN: 1420-3049, DOI: 10.3390/molecules22071101
Molecules 22/7 2019-08-07

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