Cell Host Microbe 28, 41–53 (2020)

Bacteria in the gastrointestinal (GI) tract can impact neurological function, and, conversely, host-derived neurotransmitters can affect bacterial virulence. To understand the interplay between the neurotransmitter serotonin, which is mainly synthesized in the GI tract, and bacterial virulence, Kumar et al. studied the human enteric pathogen EHEC and found that serotonin decreased virulence gene expression in EHEC, including that of genes in the locus of enterocyte effacement (LEE) required for lesion formation by the bacteria. Transcriptomic analysis showed changes in expression of both virulence genes and a histidine sensor kinase, CpxA, which has been shown to sense the structurally similar bacteria-generated compound indole and similarly decreases LEE gene expression in EHEC. Biochemical and knockout studies indicated that CpxA can act as a receptor for serotonin on EHEC and is required for its virulence. Serotonin also required CpxA to decrease LEE gene expression in the murine pathogen Citrobacter rodentium. In vivo work using genetic and pharmacologic modulators of serotonin levels found that intestinal serotonin decreases virulence gene expression in C. rodentium, leading to decreased host susceptibility to the pathogen. These results suggest an important role for the microbiota–gut–brain axis in host and pathogen physiology.

Credit: Cell Press