Acetylcholine responsiveness of the BetI regulatory system in Escherichia coli

Acetylcholine (ACh) is widely recognized as a neurotransmitter in animals; however, its potential relevance to microbial physiology remains largely unexplored. Here, we report that the BetI regulatory system of Escherichia coli, previously characterized as a choline-responsive osmoprotective pathway, exhibits a measurable transcriptional response to extracellular ACh. Using a recombinant reporter strain, we demonstrate that ACh induces BetI-dependent gene expression and that the shape and sensitivity of the response curve are markedly altered by genetic perturbations of pathway components, including BetT overexpression and BetA deletion. While the underlying molecular mechanism remains unresolved, these results establish that E. coli can functionally respond to ACh at the whole-cell level. Given that ACh is readily hydrolyzed into metabolites relevant to microbial metabolism and is supplied in animal tissues from sources beyond neurons, our findings suggest that acetylcholine responsiveness may be more widespread among host-associated microorganisms than previously appreciated.