Phd contract (M/F) DEVELOPMENT OF NEW ANTIBIOTICS ACTIVE ON SS-LACTAM-RESISTANT STRAINS OFSTAPHYLOCOCCUS AUREUS.DEVELOPMENT OF NEW ANTIBIOTICS ACTIVE ON B-LACTAM-RESISTANT STRAINS OF STAPHYLOCOCCUS AUREUS.

The thesis will be carried out at the Institut de Biologie Intégrative de la Cellule (I2BC), a joint research unit involving the CNRS,Université Paris-Saclay and the CEA. The I2BC offers exclusive access to state-of-the-art technological facilities, hosting 16 technical platforms. The subject of the thesis is directly linked to the core theme of the "Enzymology and non-ribosomal peptide synthesis" research team. This is a project in close collaboration with another research team in the Institute (structuralists from Function and architecture of macromolecular assemblies team) and other collaborators at national (Université de Strasbourg and Université Paris-cité) or international (Université KE Leuven) level. The PhD student will benefit from a dynamic environment and all the technical resources needed to carry out his or her research work (mass spectrometer coupled to high-pressure chromatography, HPLC and FPLC chains, peptide synthesizer, microbiology, biochemistry and chemistry laboratories).

The aim of this project is to synthesize a new family of antibacterials active on resistant strains of Staphylococcus aureus. The first aim is to understand how this pathogen efficiently diverts aminoacyl-tRNAs from the translational machinery for synthesis or modification of the bacterial wall, and more specifically what role post-transcriptional modifications may play in this process. The mechanistic information obtained from these studies will be used to design and synthesize specific inhibitors of aminoacyl transferases to obtain, after vectorization, compounds with antibacterial activities. These molecules will be used alone or in combination with existing antibiotics, in order to circumvent resistance phenomena in S. aureus, which are posing ever-greater public health problems worldwide.