Bacterial resistance : in search of new antibiotic agents

Despite the extensive use of antibiotic agents and the existence of vaccination programs, infectious diseases, particularly bacterial infections are still a major cause of death worldwide. Indeed, because of the massive and often inadequate use of antibiotics, pathogenic bacteria have developed resistance mechanisms against most classes of currently available antibiotics. This trend has been particularly dramatic over the past twenty years. The possible transmission of genes that encode the mechanisms of resistance between different bacterial species has led to the emergence of multiresistant bacteria. This situation causes problems in therapy, particularly in hospitals, The recent and continuous emergence of conventionally used antibiotic-resistant strains in clinic is a serious public health issue. It is urgent new antibacterial agents be discovered. Such molecules must be targeted to proteins that are essential for cell viability, but absent in mammals.

The main objects of this research work are:
-the design and the synthesis of compounds with potential antimicrobial properties depending on their chemical structure (drug design) : the targets being the enzymes involved in the biosynthetic pathway of diaminopimelic acid (DAP) and peptidoglycan or in cell signalling/general regulation of cellular functions.
-the measure of the inhibitory activity of these compounds
-the evaluation of the antimicrobial activity of these molecules in vitro on a wide range of Gram-positive and Gram-negative antibiotic-sensitive or multiresistant strains.

This project is a collaboration with :

-Bacteriology-Virology Laboratory (Laboratoire de Bactériologie-Virologie)
CHU de Nîmes /INSERM U1047, UFR de Médecine de Nîmes (Jean-Philippe LAVIGNE, PUPH)

-le Laboratoire des Enveloppes Bactériennes et Antibiotiques IBBMC, UMR 8619 CNRS Université Paris-Sud, Orsay (Dr. Dominique Mengin-Lecreulx)

-The Scripps Research Institute, La Jolla, CA, USA (Dr. Hendrik Szurmant)

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