A lipopolysaccharide (LPS) is a large molecule that contains both lipid and a carbohydrate. They are a major suprastructure of Gram-negative bacteria which contributes greatly to the structural integrity of the bacteria, and protects them from host immune defenses.
It comprises three parts: polysaccharide (O) side chains; core polysaccharides; and lipid A. Lipid A contains unusual fatty acids (e.g. hydroxy-myristic acid) and is inserted into the outer membrane while the rest of the LPS projects from the surface. Core polysaccharide contains unusual sugars (e.g. KDO, keto-deoxyoctulonate and heptulose). It contains two glucosamine sugar derivatives each containing three fatty acids with phosphate or pyrophosphate attached. The core polysaccharide is attached to lipid A, which is also in part responsible for the toxicity of gram-negative bacteria. LPS acts as the protypical endotoxin, because it binds the CD14/TLR4/MD2 receptor complex, which promotes the secretion of pro-inflammatory cytokines in many cell types. An "LPS challenge" in immunology is the exposing of the subject to an LPS which may act as a toxin.
The polysaccharide side chain is referred as the O-antigen of the bacteria. O side chain (O antigen) is also a polysaccharide chain that extends from the core polysaccharide. The composition of the O side chain varies between different gram-negative bacterial strains. O side chains are easily recognized by the antibodies of the host, however, the nature of the chain can easily be modified by Gram-negative bacteria to avoid detection. LPS also increases the negative charge of the cell wall and helps stabilize the overall membrane structure.
The making of LPS can be modified in order to present a specific sugar structure. Those can be recognised by either other LPS (which enables to inhibit LPS toxins) or glycosyltransferases which will use those sugar strucure to add more specific sugars.
O antigen ie the outer carbohydrates are supposed to be most variable imparting the antigenic specificity. In contrast lipid A is the most conserved part. However LPS lipid A composition also may vary (eg in number and nature of acyl chains even within or between genera). Some of these variations may be impart antagonistic property to these LPS. For example Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) is a potent antagonist of LPS in human cells, but is an agonist in hamster and equine cells. It has been speculated that conical Lipid A (eg from E coli) are more agonistic, less conical lipid A like those of Porphyromonas gingivalis may activate a different signal (?TLR2 instead of TLR4?), and completely cylindrical lipid A like that of Rhodobacter sphaeroides is antagonistic to TLRs. * *
LPS function, has been for several years under experimental research, due to its role in activating many transcriptional factors, which become active after stimulation with LPS. LPS also produce many types of mediators involved in septic shock.
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