Clostridial Neurotoxins How Do They Work

Clostridial neurotoxins are proteins that are produced by the anaerobic bacteria Clostridium tetani (tetanus toxin) and Clostridium botulinum (botulinum neurotoxins). Whereas tetanus toxin (TeTx) comprises a single molecular species, different strains of Clostridium botulinum produce seven different types of botulinum neurotoxin (desig- 

Aktories (Ed.), Bacterial Toxins. Chapman Hall, Weinheim, 1997. ISBN 3-8261 -0080-8 193 

Tetanus toxin poisoning produces tetanus, i.e. muscle contractions resulting in spastic paralysis. In contrast, Botulinum neurotoxins cause botulism, which is characterized by flaccid paralysis. This difference reflects differences in the anatomical level of action of these toxins. TeTx acts primarily on the CNS where it blocks exocytosis from inhibitory glycinergic synapses in the spinal cord. Loss of inhibitory control results in motoneuron firing. BoNTs act primarily in the periphery where they inhibit acetylcholine release at the neuromuscular junctions. 

Numerous studies using a variety of experimental model systems have contributed to the elucidation of the poisoning pathway of the toxins (see Niemann ef al., 1994 Ahnert-Hilger and Bigalke, 1995 and this volume. Chapter 14, for more details). Briefly, the following steps can be summarized  

Recognition and binding of the toxin to the plasma membrane of the nerve terminal Binding occurs spontaneously and with high affinity to specific receptors which include both ganglioside and protein components (Montecucco, 1986 Middlebrook, 1989 Nie-mannn, 1991 Nishiki efal., 1994). 

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