On the essentiality of lipopolysaccharide to Gram-negative bacteria

Abstract

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.

Figure 1

Pathways that mediate outer membrane (OM) biogenesis and maintain OM integrity. (A) LPS is a complex glycolipid that consists of three regions: lipid A, a core oligosaccharide and an O-antigen polysaccharide. (B) O-antigen is assembled through the Wzy-dependent pathway. The O-antigen repeat unit is assembled in the cytoplasm and flipped to the periplasmic face of the IM by Wzx; O-antigen is polymerized by Wzy and the chain length is modulated by Wzz. (C) LPS is biosynthesized in the cytoplasm, flipped to the periplasmic face of the inner membrane (IM) and transported through the periplasm to the outer leaflet of the OM via the Lpt pathway. Ligation to O-antigen depends on the particular strain background. (D) Mislocalized or misfolded OMPs and LPS loss or defects initiate the σ^E envelope stress response pathway. LPS loss or defects affect porin assembly; misassembled porin binds to DegS, degrading RseA and initiating the σ^E stress response. LPS signal could directly bind to RseB, subjecting RseA to proteolysis by DegS to activate the σ^E stress response.