Nicolas Coudray

The outer membrane (OM) of Gram-negative bacteria is an asymmetric bilayer composed of LPS in the outer leaflet and phospholipids in the inner leaflet. It constitutes a robust barrier for the cell, often making bacteria resistant to antibiotics that are unable to cross this barrier. Targeting pathways involved in maintaining the integrity of the outer membrane may be a fruitful approach for developing new antibiotics. Elucidating the structure and mechanism of proteins involved in the transport of lipids across the periplasm constitutes a step in that direction. The MCE protein family has been shown to be involved in phospholipid transport in double membraned bacteria. Using the core “MCE domain” as a fundamental building block, this protein family can adopt substantially different architectures and thus, different mechanisms, to transport lipids between membranes. Cryo EM data processing and insights gained from structures of two of these systems from E. coli will be discussed: the Mla system and the Let system. These structures provide the basis for two fundamentally different mechanisms of lipid transport in bacteria