Outer membrane biogenesis in Gram-negative bacteria 

Gram-negative bacteria have become increasingly resistant to available antibiotics resulting in more illness, healthcare costs, and deaths. Their cell envelope consists of the inner membrane (IM) surrounding the cytoplasm and an outer membrane (OM) that protects the cells from harsh conditions. The OM is an asymmetric bilayer made up of phospholipids (PL) and lipopolysaccharides (LPS). Also, the OM harbors numerous β- barrel proteins (outer membrane proteins, OMPs). Both LPS and OMPs are synthesized in the cytoplasm and subsequently transported across the periplasm into the OM. In E. coli,  seven essential proteins LptABCDEFG spanning the entire cell envelope form the LPS transport system. Similarly, The β-Barrel Assembly Machinery (BAM), which consists of the BamABCDE subunits mediates folding and insertion of OMP precursors from periplasm into the OM.

 

The Lpt System - lipopolysaccharide (LPS) transport mechanism

The Lpt system transports LPS molecules from the inner membrane to the outer membrane through a tans-periplasmic bridge consisting of LptC, LptA, and the N-terminal domain of LptD. The ABC exporter LptB2FG located in the inner membrane is suggested to extract LPS molecules and push it through the periplasm at the expense of ATP hydrolysis. Structures of the individual subunits have been resolved. We investigate how the subunits interact with each other form the supramolecular trans-envelope complex and how ATP hydrolysis at the inner membrane powers LPS transport through the periplasm into the outer membrane.