LPS (lipopolysaccharide) is a major glycolipid component of the outer membrane of Gram negative bacteria. It consists of a hydrophobic lipid A region anchored in the membrane, a core oligosaccharide, and an O‑antigen polysaccharide that extends outward.
Structure and Biological Function
Lipopolysaccharide molecules create an asymmetrical bilayer in which the outer leaflet of the bacterial outer membrane is composed almost entirely of LPS. The lipid A moiety is a phosphorylated disaccharide of glucosamine with multiple fatty acid chains; it anchors the molecule and triggers innate immune responses through the Toll‑like receptor 4–MD‑2 complex. The core region contains unusual sugars such as Kdo (3‑deoxy‑D‑manno‑octulosonic acid) and heptoses and links lipid A to the highly variable O‑antigen repeat units. The O‑antigen, composed of repeating oligosaccharide units, provides serotype‑specific antigenic diversity and contributes to complement resistance and evasion of host immunity. LPS stabilizes the outer membrane, forms a permeability barrier against hydrophobic antibiotics and detergents, and is essential for the viability of many Gram‑negative bacteria. Cells can modify lipid A phosphorylation and acylation patterns in response to environmental stresses, altering immune detection and antibiotic susceptibility.
Health Implications and Uses
When LPS molecules are shed from the bacterial surface or released upon lysis, they act as potent endotoxins. Exposure to high concentrations of lipid A can provoke fever, hypotension and disseminated intravascular coagulation, contributing to the pathogenesis of septic shock and meningococcemia. Clinically important strains such as Escherichia coli O157:H7 are defined by their O‑antigen structures, which determine serogroup and virulence. In research, purified LPS is widely used to activate macrophages and dendritic cells in vitro and to model systemic inflammation in animals. Detoxified derivatives such as monophosphoryl lipid A are used as adjuvants in several vaccines.
As both a structural component and an endotoxin, LPS plays central roles in bacterial physiology and host–pathogen interactions. Understanding its structure and biological effects informs antimicrobial development, vaccine design and the management of septic shock.
Related Terms: Endotoxin, Gram Negative Bacteria, Lipid A, O Antigen, TLR4