Verotoxin or Shiga toxin:
|Note: although Shiga toxin and Verotoxin are treated as different entities by the Australia Commission, they are structurally and functionally identical and considered the same thing by the scientific community.|
|Return to Top|
|Symptoms, Treatment, Decontamination|
The name is dependent upon the causative organism and the symptoms.
|Onset of Symptoms||Within a few hours with higher doses leading to more rapid onset of symptoms.|
|Rapid diagnostic assay||Immunoassays are available for the toxin.|
|Supportive Care||Maintain fluid and electrolytes levels, monitor and support kidney function|
|Inactivation||Steam treatment, oxidizing agents such as bleach and reactive sterilants such as glutaraldehyde.|
|There seems to be little or no published work on the inhalation toxicity of Shiga toxin. However, there are often indirect effects on the lungs when the toxin is taken in as a food contaminant.|
|Structure||The toxin is a multisubunit protein made up one molecule of A subunit (32,000 molecular weight) responsible for the toxic action of the protein, and five molecules of the B subunit (7,700 molecular weight) responsible for binding to a specific cell type.|
|Solubility||Freely soluble in water|
|pKa in water|
|Complete synthesis||No. Toxin for research purposes is manufactured by culture of producer strains or recombinant bacteria expressing the cloned genes|
The toxin acts on the lining of the blood vessels, the vascular endothelium. The B subunits of the toxin bind to a component of the cell membrane known as Gb3 and the complex enters the cell. When the protein is inside the cell, the A subunit interacts with the ribosomes to inactivate them. Like ricin A subunit, the A subunit of Shiga toxin is an N-glycosidase that modifies the RNA component of the ribosome to inactivate it and so bring a halt to protein synthesis leading to the death of the cell. The vascular endothelium has to continually renew itself, so this killing of cells leads to a breakdown of the lining and to hemorrhage. The first response is commonly a bloody diarrhea. This is because Shiga toxin is usually taken in with contaminated food or water.
The toxin is effective against small blood vessels, such as found in the digestive tract, the kidney, and lungs, but not against large vessels such as the arteries or major veins. A specific target for the toxin appears to the vascular endothelium of the glomerulus. This is the filtering structure that is a key to the function of the kidney. Destroying these structures leads to kidney failure and the development of the often deadly and frequently debilitating hemolytic uremic syndrome. Food poisoning with Shiga toxin often also has effects on the lungs and the nervous system.
The commonest sources are the bacteria Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC) of which the strain O157:H7 has become the best known. These bacteria are relatively easy to culture in the laboratory. The toxin genes have been cloned and the toxin can also be manufactured with relative safety using academic research strains of Escherichia coli that carry multiple mutations and that are too weak to survive if the escape from the laboratory.
The protein is robust, stable, relatively easy to manufacture and has been the subject of intense research over many years. This information may allow the development of defenses against, but may also be used to develop novel variants of greater effectiveness. The protein does not act through the skin, and effective protection can probably be obtained with a gas mask with activated charcoal filters.
Copyright© 1999 CBWInfo.com