Pushing the envelope: LPS modifications and their consequences

The defining feature of the Gram-negative cell envelope is the presence of two cellular membranes, with the specialized glycolipid lipopolysaccharide (LPS) exclusively found on the surface of the outer membrane. The surface layer of LPS contributes to the stringent permeability properties of the outer membrane, which is particularly resistant to permeation of many toxic compounds, including antibiotics. As a common surface antigen, LPS is recognized by host immune cells, which mount defences to clear pathogenic bacteria. To alter properties of the outer membrane or evade the host immune response, Gram-negative bacteria chemically modify LPS in a wide variety of ways. Here, we review key features and physiological consequences of LPS biogenesis and modifications. Lipopolysaccharide is a key component of the Gram-negative cell envelope and functions, for example, as a permeability barrier or determinant of host immune responses. In this Review, Simpson and Trent guide us through lipopolysaccharide biogenesis and modifications and their functional and therapeutic implications.