Chapter 4 - Genetics and Biosynthesis of Lipopolysaccharide

Abstract

Lipopolysaccharide (LPS), an integral component of the outer membrane in Gram-negative bacteria, consists of lipid A, core oligosaccharide (core), and O-specific polysaccharide or O antigen (OAg). LPS protects Gram-negative bacteria from environmental chemical and physical stress and is also recognized by the innate immune system upon infection. LPS biosynthesis, export and assembly require a large number of enzymes and structural proteins encoded by numerous genes. Both the lipid A and core are assembled on the cytoplasmic side of the inner membrane and translocated across the inner membrane. The OAg is independently assembled in a separate pathway, also translocated to the periplasmic side of the cell membrane, and ligated to the lipid A-core. Newly formed LPS is then shuttled across the periplasm by a complex multiprotein pathway, which also mediates the insertion of LPS into the outer leaflet of the outer membrane. This chapter discusses current mechanistic understanding of the synthesis and assembly of the LPS molecule.