Botulinum Toxin: Present Knowledge and Threats
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Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most toxic substance known to humans that causes the clinical condition known as botulism. The classic manifestation involves skeletal muscle paralysis as a result of a presynaptic blockade to the release of acetylcholine. Since the discovery of the toxin about 100 years ago, various clinical forms of botulism have been described comprising classic or foodborne botulism, wound botulism, infant botulism, and inadvertent botulism. Almost all human cases of botulism are caused by one of four serotypes (A, B, E, or F). Inadvertent botulism is the most recent form to be described. It occurs in patients who have been treated with injections of botulinum toxin for dystonic and other movement disorders.
Laboratory proof of botulism is established with the detection of toxin in the patient’s serum, stool, or wound. The most sensitive and widely accepted diagnostic method for BoNTs is the mouse bioassay, which takes 4 days to complete. This clearly cannot meet the immediate need for clinical diagnosis of botulism, botulinum detection in field conditions, and screening of large scale samples. Consequently, the clinical diagnosis of botulism relies on the clinical symptom development, thus limiting the effectiveness of antitoxin treatment. In response to this critical need, many in vitro methods for BoNT detection have been developed. This review is focused on the toxin structure, mechanism of action, detection methods, clinical diagnosis, and therapy including the second-generation vaccines using cell-free expression system as alternate strategy.
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