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. Last Updated: 07/27/2016

Researchers Solve Botulism Mystery




Scientists from Brookhaven National Laboratory have figured out how a toxin that causes potentially lethal botulism food poisoning does its damage, the first step in developing antidotes or preventive treatments.


Subramanyam Swaminathan, a biologist at the lab in Upton, New York, deciphered the molecular structure of one of seven known toxins produced by the Clostridium botulinum bacteria. This toxin, botulinum neurotoxin B, and several other toxins produced by the bacterium are among the deadliest in the world. According to Swaminathan, one drop can paralyze the body, including the muscles responsible for breathing.


Botulism in humans is usually linked to bacteria that develop in improperly canned or preserved foods, such as meats or nonacidic vegetables such as green beans. The Brookhaven scientists analyzed the structure of toxin B with the facility's National Synchrotron Light Source. By studying how high-intensity X-rays bounce off or pass through parts of toxin samples, the scientists constructed the shape and arrangement of the atoms that make up the molecule.


This technique allowed the biologist and his colleagues to see how the toxic molecule binds to nerve cells, triggering paralysis. Reporting in the August issue of Nature Structural Biology, the scientists said the toxin first attacks so-called ganglioside receptors on the cell's surface. These gangliosides have specific sugar molecules onto which the toxin latches. From there, it gains entry into the cell and cleaves, or cuts, a protein that is necessary for neurotransmitters to do their job. With the action of the neurotransmitter blocked, the nerves can't signal the muscles to contract. The result: weakness and paralysis.


"Understanding this mechanism will help scientists develop vaccines against this biological threat,'' said Swaminathan. He is working on the design of compounds that change the binding properties of the toxin so that it can't lock onto the sugar molecules on the ganglioside receptors. Such a therapy would be the first step in disabling this toxin, he said. It could also help in the development of better treatments for food-borne botulinum poisoning.


At the turn of the century, respiratory paralysis claimed 70 percent of people exposed to botulinum toxin. Today, thanks to ventilators, less than 2 percent of patients die, but recovery is slow.


There is an antitoxin that can neutralize the toxin, but the antidote is made from serum obtained from horses and can cause serious side effects such as a life-threatening allergic reaction. It isn't used in children. The search for new and safer therapies continues.


Interestingly, this same toxin has proved a life-saving therapy for some patients with severe movement disorders. In 1989, purified botulinum toxin was federally approved for the treatment of two eye conditions, blepharospasm and strabismus. It acts to paralyze muscles that contract too much. It is now used for the treatment of several types of dystonia, or movement disorder.