Copper (Cu) is required for various key metabolisms, yet it is cytotoxic even at low concentrations. The antimicrobial properties of Cu are used by the immune system and for anthropogenic activities in Human health and agriculture. The accumulation of Cu in the environment due to these activities is a threat to health and ecosystems and contributes to the emergence of Cu-resistant organisms. Understanding the diversity of bacterial Cu homeostasis is therefore very important to identify targets for new antimicrobial treatments. This project aims to describe a new mechanism of Cu resistance in environmental or pathogenic bacteria by targeting three model organisms (Rubrivivax gelatinosus, Vibrio cholerae and Pseudomonas aeruginosa). This unresolved mechanism occurs under anaerobic or micro-aerobic conditions and involves the periplasmic cuproprotein CopI and its yet to be identified potential partners. These homologous proteins and their potential partners will be studied by an integrative and multidisciplinary approach ranging from in vitro characterization (advanced magnetic resonance techniques, electron transfer, ...) to in vivo studies (copper resistance tests under different conditions, complementation, mutants, ...). The results of this project could constitute the basic knowledge to design new molecules targeting the Cu homeostasis pathways and able to modulate bacterial growth.
