Lipopolysaccharide (LPS) layer also called the outer membrane is the outer most layer present in the cell wall of gram negative bacteria. It is a characteristics feature of Gram negative bacteria. As in peptidoglycan biosynthesis, LPS molecules are assembled at the plasma or inner membrane.
Exception: Only one Gram positive bacteria, i.e. Listeria monocyotogenes has been found to contain an authentic lipopolysaccharide.
Lipopolysaccharide is pyrogenic (responsible for fever), and also causes endotoxic shock.The LPS is composed of three distinct units;
- A phospholipid called Lipid A; It embeds Lipolysaccharide layer in the outer leaflet. Also known as endotoxin, it is responsible for toxic effects (fever and shock). Generally it is not released until death of cell. Exception: Neisseria meningitidis, which over-produces outer membrane fragments.
- A core polysaccharide of fiver sugars linked through ketodeoxyoctulonate (KDO) to lipid A.
- O antigen: An outer polysaccharide consisting of up to 25 repeating units of 3-5 sugars. These are hydrophilic in nature. O antigen is highly varied among species. Example: E.coli O157:H7 which causes food poisoning and hemolytic uremic syndrome. O antigens are used to identify certain organisms in microbiology laboratory. O antigens are toxic and account for some of the virulence of certain gram negative bacteria.
Note: LPS is heat stable and not strongly immunogenic so it cannot be converted to a toxoid.
Mechanism of Action:
- LPS activates macrophages, leading to release of TNF-alpha, IL- 1 , and IL-6. IL- 1 is a major mediator of fever.
- Macrophage activation and products lead to tissue damage.
- Damage to the endothelium from bradykinin-induced vasodilation leads to shock.
- Coagulation (DIC) is mediated through the activation of Hageman factor.