Lipid Transport to the Bacterial Outer Membrane

Abstract

The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer with phospholipids (PLs) in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. As the problem of antibiotic resistance becomes ever more dire, there is an urgent need to understand how bacteria build and maintain this barrier. One long-standing mystery in the field is how PLs are transported to the OM. In this study, we present evidence that PL transport can occur via a high-flux, diffusive pathway. The rate of transport in this pathway is modulated by the inner membrane (IM) protein YhdP. We also show that the essential IM protein YejM, previously implicated in PL transport, actually functions to adjust OM levels of LPS by preventing degradation of the LPS key biosynthetic enzyme LpxC. These findings provide insight both into the process of LPS regulation and into the poorly understood process of anterograde PL transport.