Shigella and Shigellosis (page 4)
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© Kenneth Todar, PhD
The Shiga Toxin
The Shiga toxin, also called the verotoxin, is
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,
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
The onset of symptoms is generally within a few hours, with higher
leading to more rapid onset. There is no antidote for the toxin.
care requires maintenance of fluid and electrolyte levels, and
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
The toxicity of Shiga Toxin for the mouse (LD50) is
micrograms/kg by intravenous or intraperitoneal administration. There
no published data on the inhalation toxicity of Shiga toxin. However,
are often indirect effects on the lungs when the toxin is taken in as a
Table 2. The toxin has been
several trivial names depending on the bacterium that produces it and
gene that encodes it.
dysenteriae, type I
||Shiga toxin 1
||Shiga toxin 2
|Shiga-like toxin II,
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
Mechanism of Action
The toxin acts on the lining of the blood vessels, the vascular
The B subunits of the toxin bind to a component of the cell membrane
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.
A subunit of Shiga toxin is an N-glycosidase that modifies the RNA
of the ribosome to inactivate it and so bring a halt to protein
leading to the death of the cell. The vascular endothelium has to
renew itself, so this killing of cells leads to a breakdown of the
and to hemorrhage. The first response is commonly a bloody diarrhea.
is because Shiga toxin is usually taken in with contaminated food or
The toxin is effective against small blood vessels, such as found in
the digestive tract, the kidney, and lungs, but not against large
such as the arteries or major veins. A specific target for the toxin
to the vascular endothelium of the glomerulus. This is the filtering
that is a key to the function of the kidney. Destroying these
leads to kidney failure and the development of the often deadly and
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
E. coli (EHEC) bacteria that can cause illness ranging from mild
intestinal disease to severe kidney complications.
E. coli include the relatively important serotype E. coli
O157:H7, but other non-O157 strains, such as O111 and O26, have been
with shiga toxin production.
The incubation period for STEC ranges from 1 to 8 days, though
it is 3 to 5 days. Typical symptoms include severe abdominal cramping,
onset of watery diarrhea, frequently bloody, and sometimes vomiting and
a low-grade fever. Most often the illness is mild and self-limited
lasting 1-3 days. However, serious complications such as hemorrhagic
Hemolytic Uremic Syndrome (HUS), or postdiarrheal thrombotic
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
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
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
For mild illness, antibiotics have not been shown to shorten the
of symptoms and may make the illness more severe in some people. Severe
complications, such as hemolytic uremic syndrome, require
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