Getting The Botulinum Toxin Through The Gut

Botulism is caused when the botulinum neurotoxin (BoNT) inhibits the release of a neurotransmitter. The disease can be caused by eating toxin-contaminated food, but how the BoNT protein survives the digestive tract and reaches the bloodstream has been a mystery. Last year, a group led by Rongsheng Jin of the University of California, Irvine, demonstrated how a protein called nontoxic nonhemagglutinin (NTNHA) binds to and shields BoNT to protect it from digestive proteases. Jin and colleagues have now used electron microscopy and X-ray crystallography to study a complex of BoNT, NTNHA, and three hemagglutinin proteins that play a role in getting BoNT past intestinal cells to the blood (PLoS Pa­thog. 2013, DOI: 10.1371/journal.ppat.1003690). The researchers find that the 760-kilo­dalton complex evokes the construction of the Apollo lunar lander, with BoNT and NTNHA on top and the hemagglutinins forming “legs,” which are the parts that interact with intestinal epithelial cells. The legs land on and bind to sugars on the cells, facilitating passage of BoNT. Jin and colleagues find that dosing mice with a monosaccharide can reduce BoNT toxicity, suggesting a way to prevent—but not treat—botulism. The full protein complex could also point to ways to deliver protein drugs orally.