Bacterial neurotoxins--a thousand years later

Clostridium bacteria are responsible for the neuroparalysis in tetanus and in botulism by producing potent neurotoxins. Here we review the current developments in understanding the toxins' mode of action by deciphering the molecular basis for their function. The active forms of tetanus and botulinum neurotoxins block neurotransmitter release via a zinc-dependent protease activity. All known tetanus and botulinum toxins cleave only three key components in the synaptic vesicle docking and fusion protein complex. While tetanus and botulinum types B, D, F and G cleave VAMP/synaptobrevin, an integral membrane protein of the synaptic vesicles, two other synaptic proteins from the plasma membrane, SNAP-25 and syntaxin, are cleaved by botulinum types A and E and botulinum type C, respectively. We discuss the mechanism by which the proteolytic activity of these toxins causes a block in vesicle fusion.