Enteric botulinum neurotoxins facilitate infection by Salmonella and Shigella

Botulism is a life-threatening disease caused by botulinum neurotoxins (BoNTs) released by Clostridium bacteria. BoNTs induce a flaccid paralysis by blocking neurotransmitter release from peripheral cholinergic neurons via soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) cleavage. The enteric nervous system (ENS) controls antimicrobial defense reactions within the intestine through neuron-released mediators. Here, we show that subclinical doses of BoNT/A and BoNT/B, which are not sufficient to cause botulism when released in the intestinal lumen, paralyze ENS neurons favoring infection by prototypic bacterial pathogens such as Salmonella enterica and Shigella flexneri. The BoNTs reduce the release of mucin, decreasing the protective barrier against bacterial infection. These findings disclose previously unrecognized functions of BoNTs and roles in intestinal infections. Moreover, they indicate that BoNTs are valuable tools for investigating the ENS neuron involvement in the intestinal defense reactions.