Endotoxins are potentially toxic, natural compounds found inside pathogens such as bacteria. Classically, an "endotoxin" is a toxin, which unlike an "exotoxin", is not secreted in soluble form by live bacteria, but is a structural component in the bacteria which is released mainly when bacteria are lysed. Galunggung in 1982, showing a combination of natural events. ... A pathogen or infectious agent is a biological agent that causes disease or illness to its host. ... Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ... This article or section does not cite any references or sources. ... An exotoxin is a soluble chemical excreted by a microorganism, including bacteria, fungi, algae, and protozoa. ... Lysis (Greek lusis from luein = to separate) refers to the death of a cell by bursting, often by viral or osmotic mechanisms that compromise the integrity of the cellular membrane. ...

Lipopolysaccharide and other endotoxins

The prototypical examples of endotoxin are lipopolysaccharide (LPS) or lipo-oligo-saccharide (LOS) found in the outer membrane of various Gram-negative bacteria. The term LPS is often used exchangeably with endotoxin, owing to its historical discovery. In the 1800s it became understood that bacteria could secrete toxins into their environment, which became broadly known as "exotoxin". The term endotoxin came from the discovery that portions of Gram-negative bacteria itself can cause toxicity, hence the name endotoxin. Studies of endotoxin over the next 50 years revealed that the effects of "endotoxin" was in fact due to lipopolysaccharide. A lipopolysaccharide (LPS) is any of a class of large molecules consisting of a lipid and a polysaccharide (carbohydrate) joined by a covalent bond. ... Bacteria that are Gram-negative are not stained dark blue or violet by Gram staining, in contrast to Gram-positive bacteria. ... An exotoxin is a soluble chemical excreted by a microorganism, including bacteria, fungi, algae, and protozoa. ... // Toxic and Intoxicated redirect here – toxic has other uses, which can be found at Toxicity (disambiguation); for the state of being intoxicated by alcohol see Drunkenness. ...

There are, however, endotoxins other than LPS:

• For example, delta endotoxin of Bacillus thuringiensis makes crystal-like inclusion bodies next to the endospore inside the bacteria. It is toxic to larvae of insects feeding on plants, but is harmless to humans (as we do not possess the enzymes and receptors necessary for its processing followed by toxicity).
• The only gram positive bacteria that produces endotoxin is Listeria monocytogenes.

LPS consist of a polysaccharide (sugar) chain and a lipid moiety, known as lipid A, which is responsible for the toxic effects. The polysaccharide chain is highly variable amongst different bacteria. Endotoxins are approximately 10 kDa in size but can form large aggregates up to 1000 kDa. Humans are able to produce antibodies to endotoxins after exposure but these are generally directed at the polysaccharide chain and do not protect against a wide variety of endotoxins. Injection of a small amount of endotoxin in human volunteers produced fever, a lowering of the blood pressure, and activation of inflammation and coagulation. Endotoxins are in large part responsible for the dramatic clinical manifestations of infections with pathogenic Gram-negative bacteria, such as Neisseria meningitidis, the pathogen that causes fulminant meningitis. Binomial name Bacillus thuringiensis Berliner 1915 Bacillus thuringiensis is a Gram-positive, soil dwelling bacterium of the genus Bacillus. ... An endospore is a dormant, tough, non-reproductive structure produced by a small number of bacteria from the Firmicute family. ... Gram-positive Bacillus anthracis bacteria (purple rods) in cerebrospinal fluid sample. ... Binomial name Listeria monocytogenes Murray , 1926 Listeria monocytogenes is a Gram-positive bacterium, in the division Firmicutes, named for Joseph Lister. ... Polysaccharides (sometimes called glycans) are relatively complex carbohydrates. ... Look up moiety in Wiktionary, the free dictionary. ... The unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic masses and molecular masses. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... Binomial name Neisseria meningitidis Albrecht & Ghon, 1901 Neisseria meningitidis, also simply known as meningococcus is a gram-negative bacterium best known for its role in meningitis. ... Fulminant is any event or process which occurs suddenly, quickly and is intense and severe to the point of lethality, i. ... Meningitis is the inflammation of the protective membranes covering the central nervous system, known collectively as the meninges. ...

Mechanism

In humans, LPS binds to the lipid binding protein (LBP) in the serum which transfers it to CD14 on the cell membrane, which in turn transfers it to another non-anchored protein, MD2, which associates with Toll-like receptor-4 (TLR4). Trinomial name Homo sapiens sapiens Linnaeus, 1758 Humans, or human beings, are bipedal primates belonging to the mammalian species Homo sapiens (Latin: wise man or knowing man) in the family Hominidae (the great apes). ... CD14 is a membrane-associated glycosylphosphatidylinositol-linked protein expressed at the surface of cells, especially macrophages. ... Toll-like receptors (TLRs) are type I transmembrane proteins that serve as a key part of the innate immune system. ...

CD14 and TLR4 are present in several immune system cells (including macrophages and dendritic cells), triggering the signaling cascade for macrophage/endothelial cells to secrete pro-inflammatory cytokines and Nitric oxide that lead to "endotoxic shock". A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... Dendritic cells (DC) are immune cells and form part of the mammal immune system. ... A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens Macrophages (Greek: big eaters, makros = long, phagein = eat) are white blood cells, more specifically phagocytes, acting in the nonspecific defense as well as the specific defense system of vertebrate animals. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ... R-phrases , , , , S-phrases , , , Supplementary data page Structure and properties n, εr, etc. ...

Other than TLR4, components of gram negative cell wall may also activate other pathways which may contribute to the overall endotoxic effect.

Endotoxin contamination

Endotoxins are frequent contaminants in plasmid DNA prepared from bacteria, and must be removed from the DNA to avoid unwanted inflammatory responses prior to in vivo applications such as gene therapy. Figure 1: Schematic drawing of a bacterium with plasmids enclosed. ... The structure of part of a DNA double helix Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions for the development and function of living organisms. ... In vivo (Latin for (with)in the living). ... Gene therapy is the insertion of genes into an individuals cells and tissues to treat a disease, and hereditary diseases in particular. ...

In pharmaceutical production, it is necessary to remove all traces of endotoxin from drug product containers as even small amounts of endotoxin will cause illness, but not disease, in humans. A depyrogenation oven is used for this purpose. Temperatures in excess of 300 degrees celsius are required to break down this substance. A defined endotoxin reduction rate is a correlation between time and temperature. Based on primary packaging material as syringes or vials a glass temperature of 250°C and a holding time of 30min is typical to achieve 3log reduction on endotoxin levels. Depyrogenation refers to the removal of pyrogens from solution, most commonly from injectable pharmaceuticals. ...

A very sensitive assay for detecting presence of endotoxin is the Limulus Amebocyte Lysate assay, utilizing blood from the Horseshoe crab. Very low levels of LPS can cause coagulation of the limulus lysate due to a powerful amplification through an enzymatic cascade. An assay is a procedure where the concentration of a component part of a mixture is determined. ... Please wikify (format) this article as suggested in the Guide to layout and the Manual of Style. ... Binomial name Limulus polyphemus Linnaeus, 1758 The horseshoe crab, horsefoot, or sauce-pan (Limulus polyphemus, syn. ...

See also

• Exotoxin

An exotoxin is a soluble chemical excreted by a microorganism, including bacteria, fungi, algae, and protozoa. ...

References

• Textbook of Bacteriology
• Sofer, G.; Hagel, L. (1997). Handbook of Process Chromatography: A guide to Optimization, Scale-up, and Validation. Academic Press, 158-161. ISBN 0-12-654266-X

External links

• MeSH Endotoxins