The Shiga Toxin

The Shiga toxin, also called the verotoxin, is produced by Shigella dysenteriae and
enterohemorrhagic Escherichia coli (EHEC), of which the strain O157:H7 has become the best known.

The syndromes associated with shiga toxin include dysentery, hemorrhagic colitis, and hemolytic uremic syndrome. The name is dependent upon the causative organism and the symptoms, which may include severe diarrhea, abdominal pain, vomiting, and bloody urine (in the case of hemolytic uremic syndrome).

The onset of symptoms is generally within a few hours, with higher doses leading to more rapid onset. There is no antidote for the toxin. Supportive care requires maintenance of fluid and electrolyte levels, and monitoring and support of kidney function.

Immunoassays are available for rapid diagnosis of the toxin.

Inactivation of the toxin is achieved by steam treatment, oxidizing agents such as bleach, and chemical sterilizing agents such as glutaraldehyde.

The toxicity of Shiga Toxin for the mouse (LD₅₀) is <20 micrograms/kg by intravenous or intraperitoneal administration. There is no published data 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.

Table 2. The toxin has been given several trivial names depending on the bacterium that produces it and the gene that encodes it.

Structure of the Toxin
The toxin has a molecular weight of 68,000 da. It is a multi-subunit protein made up one molecule of an 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.

Mechanism 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. 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.

Shiga Toxin-Producing Escherichia coli (STEC)
Shiga toxin-producing Escherichia coli  is a type of enterohemorrhagic E. coli (EHEC) bacteria that can cause illness ranging from mild intestinal disease to severe kidney complications.  Enterohemorrhagic E. coli include the relatively important serotype E. coli O157:H7, but other non-O157 strains, such as O111 and O26, have been associated with shiga toxin production.

The incubation period for STEC ranges from 1 to 8 days, though typically it is 3 to 5 days. Typical symptoms include severe abdominal cramping, sudden onset of watery diarrhea, frequently bloody, and sometimes vomiting and a low-grade fever. Most often the illness is mild and self-limited generally lasting 1-3 days. However, serious complications such as hemorrhagic colitis, Hemolytic Uremic Syndrome (HUS), or postdiarrheal thrombotic thrombocytopenic purpura (TTP) can occur in up to 10% of cases.

Cases and outbreaks of Shiga toxin-producing Escherichia coli have been associated with the consumption of undercooked beef (especially ground beef), raw milk, unpasteurized apple juice, contaminated water, red leaf lettuce, alfalfa sprouts, and venison jerky. The bacteria have also been isolated from poultry, pork and lamb. Person-to-person spread via fecal-oral transmission may occur in high-risk settings like day care centers and nursing homes.

Although anyone can get infected, the highest infection rates are in children under age 5. Elderly patients also account for a large number of cases. Outbreaks have occurred in child-care facilities and nursing homes.

For mild illness, antibiotics have not been shown to shorten the duration of symptoms and may make the illness more severe in some people. Severe complications, such as hemolytic uremic syndrome, require hospitalization.