LA JOLLA, Calif., February 23, 2012 Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) and the Medical School of Hannover in Germany recently discovered how the botulinum neurotoxin, a potential bioterrorism agent, survives the hostile environment in the stomach on its journey through the human body. Their study, published February 24 in Science, reveals the first 3D structure of a neurotoxin together with its bodyguard, a protein made simultaneously in the same bacterium. The bodyguard keeps the toxin safe through the gut, then lets go as the toxin enters the bloodstream. This new information also reveals the toxin's weak spota point in the process that can be targeted with new therapeutics.
"Now that we better understand the structure of the bacterial machinery that was designed for highly efficient toxin protection and delivery, we can see more clearly how to break it," said Rongsheng Jin, Ph.D., assistant professor in Sanford-Burnham's Del E. Webb Neuroscience, Aging and Stem Cell Research Center and senior author of the study.
The Janus-faced toxin
The botulinum neurotoxin is two-faced. On one side, it's the most poisonous substance known to man, causing botulism. Accidental botulinum neurotoxin poisoning is usually food-borne, but it's also considered a potential bioterrorism agent. On the other side, botulinum neurotoxin is also used an effective therapy and popular cosmetic, such as in BOTOX.
The neurotoxin accomplishes both the good and the bad using the same trickparalyzing muscle cells by disrupting their connections with the nerves that tell them how and when to move. But before the neurotoxin can gain access to muscles and the neurons that control them, it must make a remarkable journey through the bodysurviving the digestive enzymes and extreme acidic environment in the stomach, penetrating the small intestine, and entering the bloodstream.
Sneaking a pee
|Contact: Heather Buschman, Ph.D.|
Sanford-Burnham Medical Research Institute