The bacterial secretosome for bacterial envelope biogenesis

The Gram-negative bacterial envelope is a robust line of defence against physical and chemical environmental stress, including antibiotics. Therefore, its biogenesis is of considerable interest, as well as a target to address the growing problem of antimicrobial resistance. All bacterial proteins are synthesised in the cytosol, so inner- and outer-membrane proteins, and periplasmic residents have to be transported to their final destinations via specialised protein machineries. The Sec translocon, a ubiquitous integral inner-membrane complex, is key to this process as the major gateway for protein transit from the cytosol to the cell envelope; this can be achieved during their translation, or afterwards. Proteins need to be directed into the inner-membrane (usually co-translational), otherwise SecA utilises ATP and the proton-motive-force (PMF) to drive proteins across the membrane post-translationally. These proteins are then picked up by chaperones for folding in the periplasm, or delivered to the β-barrel assembly machinery (BAM) for incorporation into the outer-membrane. The core hetero-trimeric SecYEG-complex forms the hub for an extensive network of interactions that regulate protein transport and quality control. My talk will overview recent work on the association of the translocons of the inner- (Sec) and outer-membrane (BAM), along with periplasmic chaperones for the formation of the bacterial secretosome. I will describe our findings on the structure, dynamics and orchestration of this inter-membrane assembly for efficient passage of proteins into the inner-membrane, periplasm and outer-membrane - critical for efficient envelope biogenesis.