Lipopolysaccharides
Lipopolysaccharides (LPS) are relatively thermostable (heat-insensitive) compounds made from fat-like ( lipo ) and sugar components ( polysaccharides ). They are contained in the outer membrane of gram-negative bacteria . They act as antigens and are used for the serological characterization and identification of the bacteria. When the bacteria decay, parts of them are released and have a toxic effect. These parts are known as endotoxins and are not released by intact bacteria.
In the case of short-chain sugar components ( oligosaccharides ) one also speaks of lipooligosaccharides (LOS) .
structure
Lipopolysaccharides consist of three sub-areas that are interconnected:
- Lipid A
- Lipid A forms the inner area of the LPS (or LOS), which is also anchored in the outer membrane . This part acts as an endotoxin . It becomes free after the cell is destroyed. In contrast to most other lipids of the cell membrane, lipid A is not a phospholipid : the fatty acids are bound to a disaccharide consisting of N -acetylglucosamine phosphate through ester bonds . The most common fatty acids here include caproic , lauric , myristic , palmitic and stearic acids . Lipid A can be different depending on the type of bacteria.
- Core region
- The core region is bound to lipid A and consists of an inner and an outer core region. It essentially consists of 2-keto-3-deoxy-octonate (KDO) as well as heptose , glucose, galactose and N -acetylglucosamine . The core region can also be different for different types of bacteria.
- Polysaccharide (or oligosaccharide)
- An oligo- or polysaccharide bound to the core forms the third, outer area. It forms a chain of one or more hexoses , for example rhamnose , galactose , glucose and mannose , and one or more dideoxy sugars such as abequose , colitose , paratose or tyvelose , partially modified. These sugars are linked in four- or five-part sequences that are often branched. The repetition of the sugar sequences creates the long polysaccharide. This polysaccharide is called O-polysaccharide because it acts as the bacterium's O-antigen . This area differs depending on the type and strain of bacteria and can be used to differentiate between bacteria, including differentiating between pathogenic and non-pathogenic species. Usually serological methods are used for this, especially the Gruber-Widal reaction . For example, typhoid and other salmonellosis can be distinguished.
The oligosaccharide chains can be very short or absent. In contrast, there is no lack of the core region.
biosynthesis
- Lipid A and the core region
- are synthesized in the cytoplasm and attached to one another there. This bandage is then folded through the cell membrane and is spontaneously stored in the outer membrane of the cell wall .
- Oligo / ploysaccharide chains
- are also synthesized in the cytoplasm, but they are highly hydrophilic and cannot easily be transported through the lipophilic cell membrane. So that this is still possible, undecaprenyl phosphate is bound to it. This gives it a lipophilic end through which it can be pulled through the cell membrane. In the periplasmic space , partial areas are now copied by polymerases and attached to the existing chains.
The saccharide chains are now connected to the lipid A core region association by ligases and transported into the outer membrane with the help of pores ( Bayer's junctions ). This process is passive and therefore possible without any expenditure of energy.
Reactions of the human body to endotoxic lipopolysaccharides
If lipopolysaccharides get into the blood, they bind to the serum protein lipopolysaccharide-binding protein (LBP). This complex binds to the membrane receptor CD14 , including on the monocyte surface, and induces the release of tumor necrosis factor and interleukin-1β by this CD14-bearing cell via NF-κB . The CD14 expression is in turn induced temporarily paracrine by TNF (positive self-reinforcement).
Lipopolysaccharides can pass through circumventricular organs (places with a more permeable blood-brain barrier ) directly into the brain and from there, especially in the microglia, induce their own receptor, CD14, in order to then locally stimulate the subsequent cytokine production. This is one of the ways that leads to a fever .
Destruction of lipopolysaccharides
Heat-resistant devices can be freed of lipopolysaccharides by heating them for 5 hours at 200 ° C, and non-heat-resistant devices with 1 molar sodium hydroxide solution, which should act for 15 hours.
