Transport of lipopolysaccharide across the cell envelope: the long road of discovery

In this Timeline, Silhavy and colleagues trace the experiments that revealed the structure and composition of the membranes and cell wall of Gram-negative bacteria and describe our current knowledge of the synthesis and transport pathways of lipopolysaccharide. Intracellular lipid transport is poorly understood. Genetic studies to identify lipid-transport factors are complicated by the essentiality of many lipids, whereas biochemical and cell biology approaches aiming to determine localization and mechanisms of lipid transport are often challenged by the lack of adequate technology. Here, we review the epic history of how different approaches, technological advances and ingenuity contributed to the recent discovery of a multi-protein pathway that transports lipopolysaccharide across the envelope of Gram-negative bacteria.