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Verotoxin or Shiga toxin: essential data
Symptoms and Treatment, Toxicity, Chemistry, Site of Action, Sources, Properties, Terrorist Interest, IDC Codes
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.
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Symptoms, Treatment, Decontamination
Syndrome Name	Dysentery Hemorrhagic colitis Hemolytic uremic syndrome The name is dependent upon the causative organism and the symptoms.
Symptoms	Severe diarrhea, Abdominal pain, Vomiting, Bloody urine (in the case of hemolytic uremic syndrome).
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.
Antidote	None available
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.

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Toxicity

Route	LD50(micrograms/kg)
Intravenous	<20 (mouse) 200 (rabbit)
Intraperitoneal	<20 (mouse)
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.

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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.
CA Name	None
Trivial Names	Source Organism Gene Designation Toxin Name Older Names Shigella dysenteriae, type I stx Shiga toxin (Stx) Shiga toxin Escherichia coli stx1 Shiga toxin 1 (Stx1) Shiga-like toxin I, Verotoxin 1   stx2 Shiga toxin 2 (Stx2) Shiga-like toxin II, Verotoxin 2
Registry Number
RTECS Number
Molecular Formula	Not applicable
Molecular weight	68,000
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

Site of Action

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.

Source

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.

Agent Properties

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.

Terrorist Acquisition and Attempted Use.

• None confirmed.