Editors' ChoiceHost-Microbe Interactions

Bacteria May Mess with Your Mind

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Science Signaling  21 Oct 2014:
Vol. 7, Issue 348, pp. ec289
DOI: 10.1126/scisignal.aaa1002

Pathogenic and commensal microbes influence host physiology, including behavior and nervous system function in animals. Meisel et al. and Williams et al. discovered two ways that bacteria may directly affect neuronal activity in worms and humans. Caenorhabditis elegans worms display different behaviors toward different species of bacteria. C. elegans avoid the pathogenic Pseudomonas aeruginosa, but feed on Escherichia coli. Meisel et al. showed that worms with defective DAF-7 (homologous to human transforming growth factor–β, TGF-β) signaling failed to avoid P. aeruginosa, became infected, and died. Although daf-7 is not expressed in ASJ chemosensory neurons in the absence of bacteria, within a few minutes of exposure to P. aeruginosa, but not E. coli, the expression of daf-7 increased in these neurons. Transgenic expression of daf-7 in ASJ neurons of daf-7 mutant worms restored avoidance of P. aeruginosa. The G protein α subunits GPA-2 and GPA-3 were present in ASJ neurons and required for P. aeruginosa-induced daf-7 expression and avoidance behavior. Biochemical analysis of P. aeruginosa identified the secondary metabolites pyochelin and phenazine-1-carboxamide (PCN), as molecules that stimulated daf-7 expression in ASJ neurons. Moreover, PCN elicited a very rapid (within 6 seconds) increase in calcium in ASJ neurons. Thus, metabolites from pathogenic bacteria may activate G protein signaling in neurons to stimulate a signal that promotes avoidance behavior by altering neuronal activity in C. elegans.

Williams et al. found that Clostridium sporogenes, a bacterial species commonly found in the human intestine, produce a molecule with potential neuromodulatory properties in the host. In many eukaryotic species, including fungi, plants, and animals, the metabolite tryptamine is generated from tryptophan by tryptophan decarboxylases. Among the effects of tryptamine in mammals, tryptamine activates serotonin receptors. Tryptophan decarboxylases are thought to be rare in bacteria, but Williams et al. discovered that C. sporogenes contain a functional tryptophan decarboxylase and secrete tryptamine. Screening candidates from other microbial species identified another functional tryptophan decarboxylase in Ruminococcus gnavus, and analysis of sequences from stool samples revealed that at least 10% of healthy humans harbor bacteria with homologs of these decarboxylases. Thus, the data from these two studies suggest that diverse bacteria may produce metabolites that influence host behavior by directly acting on neurons.

J. D. Meisel, O. Panda, P. Mahanti, F. C. Schroeder, D. H. Kim, Chemosensation of bacterial secondary metabolites modulates neuroendocrine signaling and behavior of C. elegans. Cell 159, 267–280 (2014). [PubMed]

B. B. Williams, A. H. Van Benschoten, P. Cimermancic, M. S. Donia, M. Zimmermann, M. Taketani, A. Ishihara, P. C. Kashyap, J. S. Fraser, M. A. Fischbach, Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe 16, 495–503 (2014). [PubMed]

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