Exotoxin

Exotoxins (also Ektotoxine, from Ancient Greek ecto ἐκto, "outside", " outside " and τοξίνη, toxins, " toxic substance" ) are secreted by bacteria toxins against which the host body can make antivenoms ( antitoxins ). Here, " leaving " the toxin so the bacterium (in contrast to endotoxin).

Exotoxins are usually proteins and therefore not thermodynamically stable, ie not heat resistant.

They can be classified into three classes:

• Membrane- damaging toxins
• AB- toxins ( have many function)
• Superantigen toxins

Membrane -damaging exotoxins

Some have catalytic properties, such as the alpha toxin produced by Clostridium perfringens and not others, such as the alpha toxin of Staphylococcus aureus. The alpha toxin produced by Clostridium perfringens is a lipase, which destabilizes the membrane by cutting the local phospholipids. The alpha toxin of Staphylococcus aureus, however, forms a polymer on the surface of the target cell, which perforates the membrane of the cell, and thus acts as a pore-forming toxin. The membrane of macrophages and leukocytes, is damaged by the staphylococci, especially Staphylococcus aureus, formed leukocidin, an exotoxin.

AB toxins

In the simplest case they consist of an A - part, which has the catalytic activity, and a B portion, which mediates specific binding to the target cell. However, there are numerous AB toxins that have more than B subunits (for example, pertussis toxin, cholera toxin, diphtheria toxin).

The inclusion of toxins into the cell occurs by receptor- mediated endocytosis ( receptor mediated endocytosis English, RME). This binds to the B moiety to a specific receptor on the target cell, whereupon the latter receives the toxin by endocytosis. The toxin is then in an endosome, which is usually acidified during its maturation. This acidification then triggers the export of the A- part from the endosome into the cytoplasm. Thus, the A- part exert its effect.

Tetanus and botulism

Are triggered these two diseases by neurotoxins produced by Clostridium tetani or Clostridium botulinum. The neurotoxins are among the AB- toxins and make an impact on neurons. These toxins are among the most potent toxins known. The lethal dose is already at a few nanograms per kilogram.

Both toxins are endopeptidases. They destroy proteins that are important for the fusion of synaptic vesicles with the membrane of neurons. This can not be released into the synapse, the neurotransmitter Inter. In the case of botulism, the release of acetylcholine ( in tetanus glycine ) is prevented, resulting in relaxation of the muscle fibers ( lasting at tetanus muscle contraction ).

AB toxins that interact with G- proteins

Another class AB toxins acting on G- proteins. These toxins are highly effective. Once the toxin is ingested RME catalyzes the transfer of a part of A- ADP Ribosylrestes of NAD to the G protein, whereby the latter is turned off. ADP Ribosylrest is appended to certain amino acids in the G- protein, such as an arginine residue at the stimulating G.alpha protein in the case of cholera toxin, or to a cysteine ​​residue of the inhibitory G.alpha protein in the case of pertussis toxin.

Inactivation of G proteins can have serious consequences for the cell, depending on which G- protein ADP- ribosylation is. Examples include the cholera toxin, and pertussis toxin, which increase the cAMP level of the cell. This is done in the case of cholera in the intestinal cells, resulting in severe diarrhea resulted. Pertussis toxin ( Bordetella pertussis ) acts on the epithelial cells of the lungs and probably on neurons, which then results in the typical symptoms of pertussis. Additionally, the toxin acts on the macrophages and thus affects the immune response.

Diphtheria

In the case of diphtheria toxin ( from Corynebacterium diphtheriae ), the elongation factor 2 ( EF2 ) by transfer of an ADP - Ribosylrestes on Diphtamid inactivated ( a modified histidine residue ). EF2 but is absolutely necessary for protein synthesis and thus for the life of the cell.

Superantigen toxins ( superantigens )

This type of exotoxin acts by activating the immune system. The main reason for the symptoms here is the immune system response to the toxin - not the effect of the toxin itself

Superantigens provide direct contact of antigen presenting cells (APC ) to T cells. Normally, antigens need to be taken up and processed by APCs before then a few T cells via MHC -TCR contact ( T cell receptor ) can be shown. Since superantigens but independently establish contact between TCR and MHC, this means a hyper stimulation of the T cells. Superantigens bind to the variable part of the β - chain. Thus, there is no specificity for epitopes. Here, then 20 to 25% are ( 0.01 % in the normal case) stimulates all T cells in the body that can trigger a strong inflammatory response throughout the body. Symptoms such as high fever, hypotension and rash may occur. At worst, it comes to toxic shock with severe damage to the organ systems through to multi- organ failure. Cause are usually the toxins of Staphylococcus aureus, streptococci rare.