High-resolution views of lipopolysaccharide translocation driven by ABC transporters MsbA and LptB₂FGC

Gram-negative bacteria possess a dual-membrane envelope, which provides defense against environmental assault, as well as formidable resistance against antibiotics. Lipopolysaccharide (LPS) is the primary lipid component in the outermost membrane leaflet of most Gram-negative bacteria, and plays critical roles in cell envelope formation. Newly synthesized LPS at the cytoplasmic side of the inner membrane is flipped across the inner membrane and pushed across the periplasm by two ATP-binding cassette transporters, MsbA and LptB₂FGC, respectively. Both transporters represent promising targets for developing new classes of antibiotics. In this review, we discuss recent advances in understanding the mechanism of LPS translocation driven by MsbA and LptB₂FGC, with a particular focus on new findings from structural studies.