Botulinum Neurotoxin: Advances in Diagnostics and Healthcare Applications

Botulinum neurotoxin (BoNT) is the most acutely toxic substance produced by a gram-positive, rodshaped bacterium called Clostridium botulinum [1, 2]. It is a 150 kDa protein comprising of a 100 kDa heavy chain that is joined to a 50 kDa light chain by a disulfide bond. The light chain of BoNT is a protease, which attacks the SNARE protein at a neuromuscular junction, thereby preventing the vesicles (storing acetylcholine) from binding to the plasma membrane (where neurotransmitter is released). Therefore, it blocks the neuromuscular transmission by preventing the release of acetylcholine and causes paralysis of muscles in botulism. There are seven distinct BoNT types designated as A-G. BoNT A, B, E and F cause disease in humans, while C and D are responsible for diseases in cows, birds and other animals. BoNT was first reported by Justinus Kerner as a ‘sausage poison’ as it was often found on improperly handled, preserved or prepared meat products. In 1895, Emile van Ermengem first recognized and isolated it from homecured ham that was implicated in botulism. C. botulinum is classified into four physiological groups (IIV) based on its ability to digest complex proteins. Groups I (proteolytic) and II (non-proteoytic) are responsible for most human botulism outbreaks, while Group III cause diseases in animals. Group IV have not been associated with any human or animal disease.