Abstract
Botulinum neurotoxins (BoNTs) are the most lethal toxins among all bacterial, animal, plant and chemical poisonous compounds. Although a great effort has been made to understand their mode of action, some questions are still open. Why, and for what benefit, have environmental bacteria that accidentally interact with their host engineered so diverse and so specific toxins targeting one of the most specialized physiological processes, the neuroexocytosis of higher organisms? The extreme potency of BoNT does not result from only one hyperactive step, but in contrast to other potent lethal toxins, from multi-step activity. The cumulative effects of the different steps, each having a limited effect, make BoNTs the most potent lethal toxins. This is a unique mode of evolution of a toxic compound, the high potency of which results from multiple steps driven by unknown selection pressure, targeting one of the most critical physiological process of higher organisms.
Highlights
Botulinum neurotoxins (BoNTs) are the most potent protein toxins among bacterial, animal, plant and chemical poisonous substances so far known, with a lethal parenteral dose for BoNT type A of about 0.2–0.3 ng/kg in mice and 1 ng/kg in human [1,2]
BoNTs are responsible for botulism, which is a rare but severe neurological disease characterized by flaccid paralysis, inhibition of secretion, and mild dysautonomia
Does this confer them some competitive advantage favoring the spreading of the neurotoxin genes among different bacterial species? The aim of this short review is to comment on the different fascinating aspects of these most potent toxins
Summary
Botulinum neurotoxins (BoNTs) are the most potent protein toxins among bacterial, animal, plant and chemical poisonous substances so far known, with a lethal parenteral dose for BoNT type A of about 0.2–0.3 ng/kg in mice and 1 ng/kg in human [1,2]. Several physiologically distinct bacteria produce closely related types of these deadly poisons These pathogens are mainly environmental bacterial from soil, sediments, and occasionally the intestinal content of man and animals. Despite the fact that they have not developed a strategy to invade and survive in a vertebrate host, these bacteria have evolved to produce a potent toxin targeting the neuroexocytosis machinery, which is designed to kill a host at a distance from the site where they replicate and grow. Does this confer them some competitive advantage favoring the spreading of the neurotoxin genes among different bacterial species? The aim of this short review is to comment on the different fascinating aspects of these most potent toxins
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