ABSTRACT
Systematic research on the mechanism of action of botulinum neurotoxin (BoNT) began with the work of Justinus Kerner, a German medical officer, who provided the first complete description of botulism while investigating outbreaks of foodborne illnesses in southwestern Germany that were linked to consumption of sausages. The seminal work of van Ermengem revealed that foodborne botulism is intoxication, not an infection, and that the toxin is not destroyed by the harsh conditions in the gastrointestinal tract. The gene coding for the first non-clostridial BoNT-like toxin was identified in Weisella oryzae, a Gram-positive non-spore-forming bacterium found in fermented rice. The exquisite selectivity of BoNT led to its use as a precise chemical tool to identify the role of cholinergic systems in synaptic transmission and for elucidating the role of neural activity and acetylcholine (ACh) secretion in mediating the consequences of disuse atrophy. The clinical syndrome of botulism reflects toxin-induced blockade of ACh release from neuromuscular and neuroeffector junctions.
