Gram-negative bacteria are among the most difficult pathogen to combat, mainly due to their unique “outer membrane” which prevents most antibiotics from entering the cell. Lipopolysaccharide (LPS) is the major component of the outer membrane, and plays critical roles in antibiotic resistance. In a recent Nature paper, the Liao lab has used single-particle cryo-electron microscopy (cryo-EM) to determine a series of structures of E. coli LptB₂FGC, illustrating the mechanism of LPS extraction out of the inner membrane. Together with their previous cryo-EM structures of MsbA (Wi et al, Nature 2017, doi: 10.1038/nature23649), the work from the Liao lab has provided a high-resolution view of how ABC transporters fuel the remarkable journey of LPS across two membranes and the periplasm. Their cryo-EM structures will also facilitate structure-based development of novel antibiotics.