C. botulinum is a large anaerobic bacillus that forms subterminal endospores. It is widely distributed in soil, sediments of lakes and ponds, and decaying vegetation. Hence, the intestinal tracts of birds, mammals and fish may occasionally contain the organism as a transient. Seven toxigenic types of the organism exist, each producing an immunologically distinct form of botulinum toxin. The toxins are designated A, B, C1, D, E, F, and G). In the U.S., type A is the most significant cause of botulism, involved in 62% of the cases. Not all strains of C. botulinum produce the botulinum toxin. Lysogenic phages encode toxin serotypes C and D, and non lysogenized bacteria (which exist in nature) do not produce the toxin. Type G toxin is thought to be plasmid encoded.

Food-borne botulism is not an infection but an intoxication since it results from the ingestion of foods that contain the preformed clostridial toxin. In this respect, it resembles staphylococcal or Bacillus cereus food poisoning. Botulism results from eating uncooked foods in which contaminating spores have germinated and produced the toxin. C. botulinum spores are relatively heat resistant and may survive the sterilizing process of improper canning procedures. The anaerobic environment produced by the canning process may further encourage the outgrowth of spores. The organisms grow best in neutral or "low acid" vegetables (>pH4.5).

Clinical symptoms of botulism begin 18-36 hours after toxin ingestion with weakness, dizziness and dryness of the mouth. Nausea and vomiting may occur. Neurologic features soon develop, including blurred vision, inability to swallow, difficulty in speech, descending weakness of skeletal muscles and respiratory paralysis.

Botulinum toxin may be transported within nerves in a manner analogous to tetanospasmin, and can thereby gain access to the CNS. However, symptomatic CNS involvement is rare.

Clostridium botulinum

Botulinum toxin is synthesized as a single polypeptide chain with a molecular weight around 150 kDa. In this form, the toxin has a relatively low potency. The toxin is nicked by a bacterial protease (or possibly by gastric proteases) to produce two chains: a light chain (the A fragment) with a molecular weight of 50 kDa; and a heavy chain (the B fragment), with a mw of 100kDa. As with tetanospasmin, the chains remain connected by a disulfide bond. The A fragment of the nicked toxin, on a molecular weight basis, becomes the most potent toxin found in nature.

Structure of the botulinum toxins
 

The heavy chain of the toxin mediates binding to presynaptic receptors. The nature of these receptors is uncertain; different toxin types seem to utilize slightly different receptors. The binding region of the toxin molecule is located near the carboxy terminus of the heavy chain. The amino terminus of the heavy chain is thought to form a channel through the membrane of the neuron allowing the light chain to enter. The toxin (A fragment) enters the cell by receptor mediated endocytosis. Once inside a neuron, different toxin types probably differ in mechanisms by which they inhibit acetylcholine release, but a mechanism similar to or identical to tetanospasmin has been reported (i.e., proteolytic cleavage of synaptobrevin II). The affected cells fail to release a neurotransmitter, thus producing paralysis of the motor system. Once damaged, the synapse is rendered permanently useless. The recovery of function requires sprouting of a new presynaptic axon and the subsequent formation of a new synapse.

As stated above, the mechanism by which acetylcholine release is prevented is not known. However, recent evidence suggests that both botulinum toxin as well as tetanus toxin are zinc-dependent endopeptidases that cleave specific proteins that are involved in excretion of neurotransmitters. Both toxins cleave a set of proteins called synaptobrevins. Synaptobrevins are found in synaptic vesicle of neurons, the vesicles responsible for release of neurotransmitters. Presumably, proteolytic cleavage of synaptobrevin II would interfere with vesicle function and release of neurotransmitters.

Each od the toxins that cause botulism is specifically neutralized by its antitoxin. Botulinum toxins can be toxoided and make good antigens for inducing protective antibody. As with tetanus, immunity to botulism does not develop, even with severe disease, because the amount of toxin necessary to induce an immune response is lethal. Repeated occurrences of botulism has been reported.

Once the botulinum toxin has bound to nerve endings, its activity is unaffected by antitoxin. Any circulating ("unfixed") toxin can be neutralized by intravenous injection of antitoxin. Therefore, individuals known to have ingested food with botulism should be treated immediately with antiserum.

A multivalent toxoid evokes good protective antibody response but its use is unjustified due to the infrequency of the disease. An experimental vaccine exists for laboratory workers.