Current mechanistic understanding of intermembrane lipid trafficking important for maintenance of bacterial outer membrane lipid asymmetry

The outer membrane (OM) of Gram-negative bacteria exhibits unique lipid asymmetry that makes it an effective permeability barrier against toxic molecules, including antibiotics. Central to the maintenance of OM lipid asymmetry is the OmpC-Mla (maintenance of lipid asymmetry) system, which mediates the retrograde transport of phospholipids from the outer leaflet of the OM to the inner membrane. The molecular mechanism(s) of this lipid trafficking process is not fully understood; however, recent advances in structural elucidations and biochemical reconstitutions have provided detailed new insights. Here, we present an integrated understanding of how the OmpC-Mla system transports mislocalized phospholipids across the bacterial cell envelope.