Modeling botulinum neurotoxin type A using 3D printing technology

Abstract

The Clostridium botulinum bacteria produce 7 different neurotoxin serotypes (types A–G) that cause botulism, and these are the most toxic proteins known to man. Botulism develops if a person ingests the toxin, or if the Clostridium bacteria grow in the intestines or wounds in the host and toxin is released. The toxin paralyzes victims by blocking the nerve's ability to communicate with muscle fibers by inhibiting the release of acetylcholine at the synaptic clefts of neuromuscular junctions. The BoNT/A crystal structure solved by the Stevens Lab revealed three domains that are involved in catalytic cleavage of SNARE proteins, translocation of the catalytic domain, and cell receptor binding (Lacy and Stevens 1998). BoNT/A's zinc‐dependant catalytic domain cuts and disables SNAP‐25, one of the major SNARE fusion proteins required for acetylcholine vesicle docking to the presynaptic membrane. Without acetylcholine to properly signal muscle contraction, breathing muscles become paralyzed and the victim eventually suffocates. Although the potential use of BoNT/A as a bioweapon is a major concern, it is also effectively used for numerous therapeutic and cosmetic purposes. The North San Diego Girls Cooperative SMART Team (Students Modeling A Research Topic) developed a model of BoNT/A using 3D printing technology.