We study central building blocks underlying the maintenance of cellular fitness and governing cellular decisions. In particular, we are interested in an essential and ubiquitous building block: protein metal cofactors, such as Fe-S clusters. Fe-S proteins have emerged very early in evolution and they still shape the functioning of all living organisms. We study how Fe-S cofactors are made and inserted in client proteins by conserved machineries. We investigate reactivity of key proteins that intervene in metabolic fluxes by channeling electron transport via highly structurally and likely spatially organized protein systems to generate an electrochemical gradient across the membrane, in several model bacteria. Aerobic life pairs with the generation of reactive oxygen species that damage proteins. We are studying how these oxidized proteins are repaired by dedicated repair systems operating in the cytoplasm but also in the cell envelope. Critically, molecular respiration is also central to adapt bacteria to certain antibiotics classes, adding perspectives to our understanding of antibiotic resistance mechanisms. We are developing genetics and single cell approaches to study these links.
Keywords : Fe-S cluster, electron transfer, oxidative stress, protein repair, antibiotics
