17 March 2006

The Seven Deadly 'Xins of Botulinum

Clostridium Botulinum is a bacterium that produces seven deadly toxins, A through G. These toxins block the neuromuscular junction and cause paralysis of muscles. The botulinum toxin A, or BoTox, can either kill or heal. When used as a biological weapon, the toxin is deadly. When used to treat pain, it can be a godsend.

This newsrelease details how scientists from UW Madison, and the University of Texas, have determined exactly how the deadly botulinum toxin A can gain entry into neurons to block their function.

Writing in the current online edition of Science, a team of researchers at the University of Wisconsin-Madison and the University of Texas report that botox latches onto a protein known as SV2 to gain entry into neurons.

"Our work shows that botox is really smart and clever," says senior author Edwin Chapman, a UW-Madison professor of physiology and an investigator of the Howard Hughes Medical Institute. "It uses SV2 to sneak into nerves like a Trojan horse."

"Botulinum neurotoxins are among the six most dangerous bioterrorism threats," adds lead author Min Dong, a UW-Madison postdoctoral researcher in the department of physiology. "Knowing the protein receptor for [botulinum toxins] can pave the way for developing anti-toxin reagents which may block the entry of toxins into cells."

The botulinum toxins, of which there are seven types, are made by a bacterium commonly found in soil, known as Clostridium botulinum. Of the seven-identified by the letters A through G--botox A lasts a particularly long time in neurons. While that feature makes it especially useful in the clinic, it also means that botox A may pose a particularly dangerous threat as a biological weapon.

The toxin enters neurons by binding to nerve endings and preventing the release of crucial chemical messengers, known as neurotransmitters, that communicate with muscles. When enough nerve endings are invaded, botox can lead to paralysis and death. ....

Chapman and his team located the exact molecular gateway through which botox penetrates cells by gathering clues from earlier research that pointed to the potential importance of tiny neural storage bins known as "synaptic vesicles." Situated at nerve endings, synaptic vesicles continually work to store and release neurotransmitters. Dozens of proteins, including SV2, work to ensure that vesicles function properly. With standard screening experiments known as "entry assays," the scientists were able to zero in on SV2. To confirm that result, they acquired mice that were genetically engineered to carry reduced amounts of SV2. Without that protein around, the researchers found that botox was unable to wreak havoc.


The entire report is here.

For those who wish to learn the bioscience of botulism, this outline with links is most helpful. Botulinum toxin has killed many people who ingested the toxin unawares. Entire families have died within hours of eating badly preserved food that contained the toxin. The new findings discussed above may help to prevent and treat this toxicity. Because the next time you hear about botulinum toxicity may be on the civil defense channel. This is not a drill.
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