Deciphering the role of endogenous neurotransmitters in bacterial biofilms

Electrophysiology—the exchange of biochemical information via ions, ion channels, and neurotransmitters—has traditionally been associated with specialized eukaryotic cells, such as neurons. However, by studying undomesticated Bacillus subtilis in their native biofilm context, we made the unexpected discovery that bacteria coordinate multicellular behaviors using ion channel-mediated electrochemical signals. Expanding this bacterial electrophysiology paradigm, we have recently found that these biofilms also produce a diverse complement of molecules typically regarded as eukaryotic neurotransmitters. Since these neurotransmitters are produced endogenously in the absence of a eukaryotic host, our data suggests a functional role for neurotransmitters in bacteria beyond host-microbe interactions. Specifically, we detected acetylcholine, norepinephrine, epinephrine, dopamine, serotonin, γ-aminobutyric acid (GABA), and histamine at significant physiological concentrations. Importantly, of the seven major neurotransmitters that we detected, only two (histamine and GABA) have known synthesis pathways in bacteria. Furthermore, the bacterial mechanisms of response to these molecules are largely unknown. Motivated by our preliminary findings, the goal of this PECASE project is to decipher the mechanisms underlying neurotransmitter production, response, and physiological function in bacterial biofilms. This knowledge will transform our understanding of microbiology by expanding the bacterial electrophysiology paradigm to include neurotransmitters, ultimately leading to a more complete view of the emerging human microbiome gut-brain axis.