Clostridium botulinumtoxin
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The toxin inhibits release of acetylcholine from nerve endings in muscle (at the neuromuscular junction), preventing the muscle from responding to instructions from the brain.
At the molecular level, the toxin enters the nerve by binding to a protein on the surface of the cell. Each of the toxin subtypes binds to a different protein. It prevents the release of acetylcholine by blocking the interaction between the synaptic vesicles (the structures within which acetylcholine is stored) and the cell membrane that leads to acetylcholine release and transmission of the impulse. The toxin acts as an enzyme, a protease, that breaks down the protein complex that the vesicle binds to.
The toxins catalytic action means that it may take only one or two molecules to completely inactivate a nerve ending. In comparison, a toxin that simply blocked the interaction would require several hundred or thousand molecules per cell to be effective.
Symptoms, Treatment, Decontamination | |
Syndrome Name | Botulism |
Symptoms | A limp paralysis that starts at the head and descends through the body, affecting both sides of the body. This manifests itself as drooping eyelids (ptosis), weakness, dizziness, dry mouth and throat, blurred and double vision, loss of coordination and difficulty breathing. Despite the severity of the symptoms, the victim remains alert and shows no sign of fever. |
Onset of Symptoms | Typically 24-36 h after exposure. Very low-level exposure may take several days to develop symptoms. A rapid onset (<12h) indicates heavy exposure and a poor prognosis. |
Rapid diagnostic assay | Immunoassay for toxin in body fluids is available but it is likely to be unhelpful in diagnosis of poisoning via aerosols. |
Antidote | Antitoxin. Current antitoxins are effective against the three commonest forms of the toxin and do not cover all 7 known variants. Pentavalent and heptavalent antitoxins are Investigational New Drugs in the United States. |
Supportive Care | Artificial respiration to support breathing, tracheostomy may be needed. |
Prophylaxis | Vaccines using a toxoid (inactivated toxin) are available. |
Inactivation | Treatment with formaldehyde or hypochlorite bleach. The toxin is heat sensitive and boiling of contaminated objects for 10 mins. can be used. Soap and water are also effective |
International Disease Classification Codes for Botulinus Toxin Poisoning | ||
Disease | ICD-9-CM | ICD-10 |
Botulism | 005.1 | A05.1 |
Toxicity | |
Route | LD50 |
Intravenous (mouse) | 0.0003 micrograms/kg |
Inhalation (human) | 0.02 mg/min/m3 |
Chemical Properties | |
Structure | A very large protein that has two subunits in its mature form. There are seven known subtypes (A-G) of the toxin. |
CA Name | Botulin |
Trivial Names |
|
Registry Number | 107231-12-9 |
RTECS Number | |
Molecular Formula | Not applicable |
Molecular weight | Approx. 150,000 |
Solubility | Soluble in water |
pKa in water | |
Complete synthesis | Chemical synthesis is impractical. Toxin can be manufactured by fermentation of Clostridium botulinum or a producer microorganism expressing the cloned gene for the toxin. |
Source
Cultures of Clostridium botulinum: naturally-occurring cases of botulism arise from food spoiling in the absence of oxygen. The commonest source historically has been spoiled meat, notably sausage (the species name derives from the Latin botulus meaning "sausage") and poultry (especially duck), and improperly sterilized canned foods. The commonest form of botulism in the US is type E, a form associated with contaminated fish.
Agent Properties
Botulinus toxin is the most poisonous substance known and the microorganism that manufactures it is relatively easy to isolate from nature and to culture. The only problem is making sure that oxygen is excluded from cultures. Despite its large size, the toxin molecule is stable enough to be dispersed as an aerosol.
The toxin was considered for use as a weapon by Britain and Japan during the 1930's and there are suggestions that it was used by the Japanese to poison streams used as water sources by the Soviets. It has also been suggested that either the microorganism or the toxin were incorporated into grenades used in the assassination of the Reinhard Gehlen, Hitler's likely successor and Reichsprotektor of Czechoslovakia.
Terrorist Acquisition and Attempted Use.
- The German RAF (Rote Armee Faktion) are believed to have manufactured the toxin in a safe house in Paris in the 1980's.
- Aum Shinrikyo are believed to have attempted attacks on the US Embassy in Tokyo with the toxin.
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