But what is botulism, exactly, and how/why is it so lethal?
There
are actually three different ways to get botulism. The
most common occurs when a person eats improperly canned food, usually
food canned at home. It is also possible for human infants to
get botulism when they are fed something that contains live spores.
Most often, the culprits are honey, corn syrup, or similar
sweeteners. (Infants should never
be given these, even in very small quantities; up to
13% of honey samples contain C. botulinum
spores.) The early immune system can't fight them off, the
spores germinate into active bacteria, and produce toxin. The
third
means of acquiring botulism is to get the botulism bacteria or spores
into an open wound. The bacteria have to multiply in order to
produce toxin.
Note that death is not caused by overwhelming infection. Rather, death is caused by action of the toxin produced by the bacteria. The bacteria, incidentally, are Clostridium botulinum, closely related to Clostridium difficile, the cause of antibiotic-associated colitis.
Botulinum toxin is one of the most toxic substances known: 0.001 micrograms per kilogram will kill 50% of people. That toxicity is four to five orders of magnitude greater than that of nerve gas.
The reason this is of interest to someone interested in neuroscience, is that the botulinum toxin acts upon neurons. Specifically, it acts at the neuromuscular junction, causing paralysis. A single molecule is capable of disabling one neuron. The binding of the toxin is highly specific for neurons, so very little of it is "wasted" by acting on cells that it cannot disable.
Botulinum toxin is a peptide.
There are seven different
versions, A, B, C1, D, E, F, and G. They all have similar
structures and mechanisms of action. The toxin is produced
initially as a single chain of amino acids. It then is
cleaved at a specific point, causing it to become active. The
longer chain binds to structures on the surface of the nerve cell.
The toxin then introduces the short chain to the inside of
the neuron. The short chain acts by destroying important
proteins. The proteins it destroys are needed for the nerve
cell to be able to release its neurotransmitter. If the
neuron cannot release any neurotransmitter, it cannot
function. (There are some
exceptions, but the neuromuscular junction is not one of the
exceptions.)
The specificity of binding is due to a two-step process. First the toxin binds to a protein, synaptotagmin. Then a different part of the toxin binds to a ganglioside. The dual binding orients the toxin in the direction needed for it to introduce the short chain into the neuron.
Recently, some interesting work has been done on developing a potent, specific antidote. As of now (2007) there is no such antidote available. If the illness is diagnosed early enough, it is possible to give an antiserum. The antiserum contains antibodies derived from horses. The antibody binds to the toxin, preventing the toxin from binding to the neuron. Unfortunately, some people are allergic to the antiserum. Some human-derived antiserum is available, but only in extremely limited quantities. It is approved for use only in infants.
The only other treatment is supportive, meaning that the person breathes with the assistance of a mechanical ventilator, and is given IV fluids and nutrition.
Note that death is not caused by overwhelming infection. Rather, death is caused by action of the toxin produced by the bacteria. The bacteria, incidentally, are Clostridium botulinum, closely related to Clostridium difficile, the cause of antibiotic-associated colitis.
Botulinum toxin is one of the most toxic substances known: 0.001 micrograms per kilogram will kill 50% of people. That toxicity is four to five orders of magnitude greater than that of nerve gas.
The reason this is of interest to someone interested in neuroscience, is that the botulinum toxin acts upon neurons. Specifically, it acts at the neuromuscular junction, causing paralysis. A single molecule is capable of disabling one neuron. The binding of the toxin is highly specific for neurons, so very little of it is "wasted" by acting on cells that it cannot disable.
Botulinum toxin is a peptide.
There are seven different
versions, A, B, C1, D, E, F, and G. They all have similar
structures and mechanisms of action. The toxin is produced
initially as a single chain of amino acids. It then is
cleaved at a specific point, causing it to become active. The
longer chain binds to structures on the surface of the nerve cell.
The toxin then introduces the short chain to the inside of
the neuron. The short chain acts by destroying important
proteins. The proteins it destroys are needed for the nerve
cell to be able to release its neurotransmitter. If the
neuron cannot release any neurotransmitter, it cannot
function. (There are some
exceptions, but the neuromuscular junction is not one of the
exceptions.)The specificity of binding is due to a two-step process. First the toxin binds to a protein, synaptotagmin. Then a different part of the toxin binds to a ganglioside. The dual binding orients the toxin in the direction needed for it to introduce the short chain into the neuron.
Recently, some interesting work has been done on developing a potent, specific antidote. As of now (2007) there is no such antidote available. If the illness is diagnosed early enough, it is possible to give an antiserum. The antiserum contains antibodies derived from horses. The antibody binds to the toxin, preventing the toxin from binding to the neuron. Unfortunately, some people are allergic to the antiserum. Some human-derived antiserum is available, but only in extremely limited quantities. It is approved for use only in infants.
The only other treatment is supportive, meaning that the person breathes with the assistance of a mechanical ventilator, and is given IV fluids and nutrition.
