Lipopolysaccharide and Its Constituents

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Lipopolysaccharide and its constituents

Lipopolysaccharide (LPS) is a molecule that is a constituent of the outer membrane of Gram-negative bacteria . The molecule can also be referred to as endotoxin. LPS can help protect the bacterium from host defenses and can contribute to illness in the host.

The LPS comprises much of the portion of the outer membrane that is oriented towards the outside of the bacterium. There are fewer phospholipid molecules in this outer "leaflet" of the membrane than there are on the inner side of the membrane. Thus, because of the presence of lipopolysaccahride, the construction of the outer membrane is asymmetric. In contrast, the inner membrane of Gram-negative bacteria and the single membrane of Gram-positive bacteria are more symmetric, with both leaflets of the membrane comprised of much the same molecules.

A complete LPS consists of a lipid portion and a chain of sugar. The lipid region is anchored into the inner portion of the membrane by a molecule called lipid A. A core polysaccharide is also considered part of the lipid region. This core contains a compound known as 2-keto-3-deoxyoctonic acid, or KDO. The lipid A and KDO portions of LPS are common to all bacterial LPS.

The other region of LPS is the sugar chain. This portion is also known as the O-antigen. The O-antigen gets its name from the fact that it is exposed to the external environment and will be the target of antibody formation by the host. The hydrophilic ("water-loving") sugar side chain extends outward from the surface of the cell into the watery environment that typically surrounds many Gram-negative bacteria. There are many chemical arrangements of the sugar chain.

The manufacture of LPS is a multi-step process involving many enzymes . The complete LPS molecule is incorporated into the outer membrane. The biosynthetic pathway of LPS was deduced by the isolation of mutants defective in LPS assembly.

LPS can be detected using microscopic techniques following the binding of LPS specific antibody . Additionally, a biochemical test can be done. The test utilizes a compound that is obtained from the horseshoe crab.

Not all bacteria have a complete sugar chain. Depending on the bacterial species a portion of the sugar chain can be present, or sugar chain may be entirely absent. The various LPS chemistries have an affect on the appearance of the bacteria when they are grown as colonies on solid growth media. Those bacteria with the complete side chain can appear smooth and even wet, whereas those with no side chain often appear crinkly and dry. For this reason, bacteria having the complete LPS are known as smooth strains and those bacteria with no sugar side chain are designated as rough strains. Those species of bacteria that are in between, having a portion of the sugar side chain, are called semi-rough strains.

The composition of the LPS also affects the overall chemistry of the bacterial surface. Because the sugar chains protruding from the surface are hydrophilic, the bacterium tends to prefer watery environments. In contrast the lack of the side chains exposes the hydrophobic ("water hating") lipid portion of the LPS. The surface of such bacteria tends to be more hydrophobic. In solution, the rough bacteria tend to clump together in an effort to avoid the water. Antibacterial compounds that are hydrophobic are more likely to penetrate into rough strains than into smooth strains. In the intestinal tract of warm-blooded animals, where many Gram-negative bacteria live, the possession of a complete LPS is advantageous for the absorption of hydrophilic nutrients by the bacteria.

The LPS structure has a profound influence on the potential of infectious Gram-negative bacteria to establish an infection in humans and other animals. The sugar chains of smooth LPS can overlay the surface proteins of the outer membrane, masking the proteins from immune detection. Also, a bacterium can vary the chemistry of the O-antigen, so as to make the targeting of antibodies to the bacterial surface even more difficult. In contrast, the immune response to a rough strain, where the surface proteins are not camouflaged, is greater and more consistent.

Lipopolysaccharide is medically important to humans. When free from the bacterium, LPS is toxic. The portion of the LPS that is responsible for the toxicity is the core and lipid A portion (the endotoxin). Endotoxin can produce a fever, decrease in the number of white blood cells, and damage to blood vessels resulting in reduced blood pressure. At high enough endotoxin concentrations, shock can set in and death can occur.

See also Bacterial membranes and cell wall; Enterotoxin and exotoxin; Immunization