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.

Outer membrane biogenesis is a complex process for Gram-negative bacteria as the components are synthesized in the cytoplasm or at the inner membrane and then transported to the outer membrane. Stress pathways monitor and respond to problems encountered in assembling the outer membrane. The two-component system CpxAR was recently reported to be a stress pathway for transport of lipoproteins to the outer membrane, but it was unclear how this stress is sensed. May et al. [K.L. May, K.M. Lehman, A.M.Mitchell, and M. Grabowicz, mBio 10(3): e00618-19, 2019, https://doi.org/10.1128/mBio.00618-19] determined that an outer membrane lipoprotein, NlpE, is the sensor for lipoprotein biogenesis stress. The group demonstrated that CpxAR is activated by the N-terminal domain of NlpE when the lipoprotein accumulates at the inner membrane. Further, this work resolved a previously debated role for NlpE in sensing copper stress; copper was shown to inhibit acylation of lipoproteins, preventing them from being transported to the outer membrane.

Asymmetry in the outer membrane has long defined the cell envelope of Gram-negative bacteria. This asymmetry, with lipopolysaccharide (LPS) or lipooligosaccharide (LOS) exclusively in the outer leaflet of the membrane, establishes an impermeable barrier that protects the cell from a number of stressors in the environment. Work done over the past 5 years has shown that Acinetobacter baumannii has the remarkable capability to survive with inactivated production of lipid A biosynthesis and the absence of LOS in its outer membrane. The implications of LOS-deficient A. baumannii are far-reaching - from impacts on cell envelope biogenesis and maintenance, bacterial physiology, antibiotic resistance and virulence. This review examines recent work that has contributed to our understanding of LOS-deficiency and compares it to studies done on Neisseria meningitidis and Moraxella catarrhalis; the two other organisms with this capability.