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Inhibition of new targets for fighting antibiotic resistance

Objective

The introduction of antibiotics in the medical practice has drastically reduced illness and death from infectious diseases. However, bacteria have exhibited a remarkable capacity to become resistant to commonly used antibacterial compounds. In parallel to efforts aimed at better understanding the strikingly diverse mechanisms they use, it is important to design strategies which will allow to counteract them and to search for new targets, ideally essential and specific to bacterial physiology. Our approach i s based on the well established facts that peptidoglycan biosynthesis and cell morphogenesis are related phenomena and that they are totally specific to bacterial cells, without even remotely equivalent processes in eukaryotic cells. By attempting to int erfere with these processes by inhibiting enzyme activities or perturbing protein-protein interactions, one should be able to design new antibacterial compounds active against pathogenic organisms such as streptococci, staphylococci, enterococci or chlamyd iae. Five workpackages will provide converging approaches to the same general goal. 1 The study and the design of inhibitors for penicillin-resistant transpeptidases. 2 The development of inhibitors of the glycosyltransferase domain of class A penicillin-binding proteins. 3 The study and the design of inhibitors for the synthesis and transport steps of cell wall subunits located at the plasma membrane. 4 The study and the design of inhibitors for the synthesis of soluble peptidoglycan precursors. 5 The s tudy of cell morphogenesis and of its regulation and the design of compounds which might interfere with these processes. This ambitious project will lead to new insights into bacterial physiology and might have a pronounced impact in other areas includin g biotechnology, and bacterial pathogenesis. Indeed, this project will create renewed interest in these key areas and pave the way to innovative for fighting resistance to antibiotics.

Call for proposal

FP6-2003-LIFESCIHEALTH-I
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Funding Scheme

NoE - Network of Excellence

Coordinator

UNIVERSITÉ DE LIÈGE
Address
Place Du Xx Août, 7
Liège
Belgium

Participants (14)

UNIVERSITEIT VAN AMSTERDAM
Netherlands
Address
Spui 21
Amsterdam
UNIVERSITE PARIS-SUD
France
Address
15, Rue Georges Clémenceau
Orsay
UTRECHT UNIVERSITY
Netherlands
Address
Padualaan 8
Utrecht
EBERHARD-KARLS-UNIVERSITAET TUEBINGEN
Germany
Address
Wilhelmstrasse 5
Tuebingen
UNIVERSITY OF KAISERSLAUTERN
Germany
Address
Gottlieb Daimler Strasse
3049 Kaiserslautern
THE UNIVERSITY OF LEEDS
United Kingdom
CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
University Offices, Wellington Square
Oxford
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
3 Rue Michel Ange
Paris
FACULTY OF PHARMACY, UNIVERSITY OF LJUBLJANA
Slovenia
Address
Askerceva 7
Ljubljana
LEK PHARMACEUTICALS D.D.
Slovenia
Address
Verovskova 57
Ljubljana
PROTNETEOMIX SAS
France
Address
2, Rue De La Houssinière
Nantes
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
Address
6 Kensington Terrace
Newcastle Upon Tyne
COMMISARIAT À L'ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
France
Address
31/33 Rue De La Fédération
Paris
LNSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE
France
Address
101 Rue De Tolbiac
Paris