There
was an outbreak of botulism in the past several days in the
United States. The problem was traced to contaminated canned
chili sauce intended for use on hotdogs. Product from
Castleberry Food Company based in Augusta, Georgia is suspected.
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;
href="http://www.cfsan.fda.gov/%7Eebam/bam-17.html">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
href="http://www.gulflink.osd.mil/bw/bw_refs/n23en117/botulinum.htm">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,
href="http://www.tjclarkdirect.com/bacterial_diseases/tetanus_and_botulism.htm">it
acts at the neuromuscular junction, causing paralysis.
href="http://www.scripps.edu/newsandviews/e_20061218/stevens.html">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.
href="http://www.tjclarkdirect.com/bacterial_diseases/tetanus_and_botulism.htm">
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
href="http://scienceblogs.com/neurophilosophy/2007/07/nerve_function_without_action.php">some
exceptions, but the neuromuscular junction is not one of the
exceptions.)
The specificity of binding is due to a
href="http://www.scripps.edu/newsandviews/e_20061218/stevens.html">two-step
process. First the toxin binds to a protein,
href="http://en.wikipedia.org/wiki/Synaptotagmin">synaptotagmin.
Then a different part of the toxin binds to a
href="http://en.wikipedia.org/wiki/Ganglioside">ganglioside.
The dual binding orients the toxin in the direction needed
for it to introduce the short chain into the neuron.
Recently, some
href="http://pubs.acs.org/cgi-bin/article.cgi/bichaw/2002/41/i31/html/bi020060c.html">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
href="http://www.fda.gov/cber/products/igivcdhs102303.htm">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.
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