Low Intestinal Doses of Botulinum Neurotoxins types A and B favour infection by Salmonella and Shigella without the flaccid paralysis of botulism

Abstract

Botulism is a life-threatening disease characterized by a descending flaccid paralysis caused by a protein neurotoxin (BoNT) released by different anaerobic bacterial species of the genus Clostridium. The paralysis results from blockade of neurotransmitter release from the terminals of peripheral cholinergic, skeletal and autonomic neurons exerted by BoNT through the cleavage of SNARE proteins, which are essential for neuroexocytosis. Here, we investigated the effect of different doses of BoNT serotypes A and B, the serotypes most commonly associated with human botulism, on enteric nervous system neurons which play an important role in gut health and physiology. We found that BoNT/A and BoNT/B enter cholinergic neurons where they cleave SNARE proteins even at doses that do not cause signs of flaccid neuroparalysis. However, these low BoNT doses favour the invasion and infection of the mouse body by Salmonella thyphimurium and Shigella flexneri. This may have significant animal health implications.