[12] Isolation and characterization of the Botulinum neurotoxins

This chapter describes the isolation and characterization of Clostridium botulinum neurotoxins. Clostridium botulinum is an anaerobic, spore-forming organism that is relatively ubiquitous in its distribution. The bacterium is known for its ability to produce two remarkably potent toxins. The first of these is a neurotoxin that acts preferentially on cholinergic nerve endings to block the release of acetylcholine. The second is a more diffusely acting toxin that, among other things, appears to promote the movement of fluid across membranes. Botulinum neurotoxin is isolated in seven immunologically distinct forms designated A, B, C, D, E, F, and G. Although the various neurotoxins are immunologically distinct—for example, there is little cross-neutralization, they do share certain structural and functional properties. In addition, pharmacological experiments suggest that the various serotypes may proceed through the same general sequence of events in producing blockade of transmitter release. The tendency to form complexes with certain other proteins is a characteristic of most of the botulinum neurotoxins.