Abstract
Tetanus and botulinum neurotoxins are the most poisonous substances known, so much so as to be considered for a possible terrorist use. At the same time, botulinum neurotoxin type A1 is successfully used to treat a variety of human syndromes characterized by hyperactive cholinergic nerve terminals. The extreme toxicity of these neurotoxins is due to their neurospecificity and to their metalloprotease activity, which results in the deadly paralysis of tetanus and botulism. Recently, many novel botulinum neurotoxins and some botulinum-like toxins have been discovered. This large number of toxins differs in terms of toxicity and biological activity, providing a potential goldmine for novel therapeutics and for new molecular tools to dissect vesicular trafficking, fusion, and exocytosis. The scattered data on toxicity present in the literature require a systematic organization to be usable by scientists and clinicians. We have assembled here the data available in the literature on the toxicity of these toxins in different animal species. The internal comparison of these data provides insights on the biological activity of these toxins.
Highlights
Microorganisms produce hundreds and hundreds of different protein toxins that act with different mechanisms to subvert the defense systems and physiology of their hosts to the advantage of the toxigenic species
It should be considered that toxicity figures may suffer from limitations derived from multiple factors: (1) toxins of different purity were used in different reports, in the past, when methods to define the chemical and physical homogeneity of a protein preparation were not standardized; (2) in older papers, toxicity was expressed as the minimal lethal dose, that is defined as the minimal dose of toxin capable of killing the injected animal, but there is variation among different experimenters about the number of animals to be used and of time to death [17]; (3) amounts of protein toxins were, in the past, frequently measured not in units of weight of the toxin, but, rather, in flocculating units or in milligrams of nitrogen
Clostridial neurotoxins are the most potent toxins, and their extraordinary toxicity in different animal species has been long known, especially from studies performed in the past century
Summary
Microorganisms produce hundreds and hundreds of different protein toxins that act with different mechanisms to subvert the defense systems and physiology of their hosts (vertebrates, invertebrates, and plants) to the advantage of the toxigenic species. The toxicity of bacterial toxins acting on vertebrates has been traditionally tested in laboratory animals, and most of the recent data are determined in selected mice strains. These in vivo methods are progressively substituted by in vitro methods, which, have not reached the physiological complexity of the animal hosts where these toxins act to cause disease. We present tables of toxicity for TeNT and for the many BoNTs in mice, and in all other animals for which toxicity data are available. These tables include values obtained with different ways of inoculation and in different organisms
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