On the essentiality of lipopolysaccharide to Gram-negative bacteria

•We discuss the cellular role of lipopolysaccharide within Gram-negative bacteria.•We propose explanations for why lipopolysaccharide is essential in certain organisms.•We consider implications for developing lipopolysaccharide-targeting antibiotics.

Lipopolysaccharide is a highly acylated saccharolipid located on the outer leaflet of the outer membrane of Gram-negative bacteria. Lipopolysaccharide is critical to maintaining the barrier function preventing the passive diffusion of hydrophobic solutes such as antibiotics and detergents into the cell. Lipopolysaccharide has been considered an essential component for outer membrane biogenesis and cell viability based on pioneering studies in the model Gram-negative organisms Escherichia coli and Salmonella. With the isolation of lipopolysaccharide-null mutants in Neisseria meningitidis, Moraxella catarrhalis, and most recently in Acinetobacter baumannii, it has become increasingly apparent that lipopolysaccharide is not an essential outer membrane building block in all organisms. We suggest the accumulation of toxic intermediates, misassembly of essential outer membrane porins, and outer membrane stress response pathways that are activated by mislocalized lipopolysaccharide may collectively contribute to the observed strain-dependent essentiality of lipopolysaccharide.