The Origin of Clostridial Neurotoxins

Tetanus is a syndrome that is often lethal, characterized by a spastic paralysis. Death follows bodily exhaustion and occurs by respiratory failure or circulatory collapse. For twenty four centuries tetanus had been considered a neurologic disease until the identification of Clostridium tefani, the bacterium that causes tetanus by the release of a protein toxin, named tetanus neurotoxin (TeTx)(Faber, 1890 Kitasato,  

The extreme toxicity of clostridial neurotoxins (CNTs) derives from their absolute neurospecificity as well as from catalytic activity. TeTx and BoNTs bind specifically to the neuromuscular junction (NMJ) of motor neurons. The identity of the receptor(s) on the presynaptic membrane is unknown, but their extreme toxicity suggests that the binding affinity to the cognate receptor must be very high. The receptor-bound toxin is internalized at the presynaptic membrane of the NMJ and gains access to the neuronal cytosol. Here it blocks the release of acetylcholine (ACh), causing a flaccid paralysis (Simpson, 

TeTx also binds to the presynaptic membrane of the motor neuron, but its action is limited to the level of the central nervous system. 

TeTx undergoes retrograde transport inside the motor neuron to the spinal cord (Bruschettini, 1892 Vallee and Bloom, 1991), where it migrates trans-synaptically into inhibitory interneurons (Simpson, 1989). 

Aktories (Ed.), Bacterial Toxins. Chapman Hall, Weinheim, 1997. ISBN 3-8261-0080-8 pl69  

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