Clostridial Neurotoxins: Current Diagnosis and Therapeutic Approach

Clostridium is a Gram-positive, anaerobic, endo spore-forming bacillus, species of Clostridium, notably C. botulinum and C. tetani, have ability to produce potent neurotoxins. Clostridial neurotoxins include botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT). They are the most potent toxins to mankind. Botulism and tetanus are responsible for severe neurological diseases, respectively. While BoNTs cause flaccid paralysis, TeNT causes spastic paralysis. Eventually, both BoNTs and TeNT will lead to respiratory failure and death. Tetanus is mainly caused by deep penetrating wounds where anaerobic bacterial growth is facilitated. Human botulism, however, can occur in one of three natural forms: foodborne, wound, and intestinal. While inhalational botulism does not occur naturally, it is a concern as a potential bioterror attack. In BoNT the current antitoxin is a heptavalent polyclonal antibody formulation which contains neutralizing antibodies against seven toxin serotypes; A, B, C, D, E, F, and G and has superseded the older trivalent antitoxin which is only able to neutralize serotypes A, B, and E. For TeNT, Wounds from which the infection originated should be surgically debrided and an antibiotic administered. Penicillin has been the worldwide antibiotic of choice. However, the structure of penicillin is similar to γ aminobutyric acid (GABA); it therefore acts as a competitive GABA antagonist, and in high doses may cause central nervous system (CNS) hyperexcitability and convulsions. In tetanus this potential side effect of penicillin may act synergistically with the toxin to block GABA neuronal activity. Metronidazole is therefore considered to be the antibiotic of choice in the treatment of tetanus.