TROjAN

This project is part of the critical field of research that concerns bacterial resistance. Today, the efficacy of the most widely used therapeutic class, the ß-lactam agents, and especially the last-resort carbapenems, is endangered by the worldwide dissemination of extensively- or pan-drug resistant strains, including carbapenemase-producing isolates. To fight this major threat, several strategies are ongoing including drug repositioning approaches. In this field, one of the most promising therapeutic class is nucleoside analogues thanks to their pleiotropic and fundamental roles in life. The development of alternative ways to fight bacterial resistance is crucial. We propose to take over one of the mechanism of bacterial resistance to reach a selective antibacterial delivery of nucleoside analogs. These prodrugs may have a broad-spectrum activity especially toward the Gram-negative pathogens, which are highly resistant and involved in numerous severe hospital infections. Thanks to specific drug targeting into the bacterial periplasm, the antibiotic effects will be increased while side effects may be reduced. The aim of this project is to propose a new way to negate the bacterial resistance. To meet this ambitious challenge, a cross-functional team is proposed based on two complementary fields: medicinal chemistry and microbiology.