lipopolysaccharides

Lipopolysaccharides (LPS) are large, amphipathic molecules that form the outer leaflet of the outer membrane of most Gram-negative bacteria. LPS is typically described as consisting of three regions: lipid A, the core polysaccharide, and the O-antigen, a long, variable chain of sugars.

Lipid A is the hydrophobic anchor of LPS, a disaccharide of glucosamine that is N-acylated and phosphorylated. It is the primary determinant of endotoxic activity in mammals. The core polysaccharide links lipid A to the O-antigen and contains unusual sugars such as 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) and heptose residues. The O-antigen is a repeating oligosaccharide unit whose composition and linkage vary between species and strains, giving rise to numerous serotypes. Many laboratory and pathogenic strains possess full-length O-antigen, while rough mutants lack it.

Functionally, LPS contributes to the structural integrity and permeability barrier of the Gram-negative outer membrane. It also serves as a potent endotoxin: lipid A activates the host innate immune system by engaging the TLR4–MD-2–CD14 receptor complex, triggering cytokine release and inflammation. The degree of activity depends on the acylation and phosphorylation pattern of lipid A and on the presence and structure of the O-antigen.

Clinical and research relevance: LPS is a major cause of fever and septic shock in Gram-negative infections and is routinely detected in clinical settings using assays such as the Limulus amebocyte lysate test. In research, LPS is used to stimulate immune responses; O-antigen and core polysaccharide components are targets for diagnostics and vaccine development.