Dokument

Summary:
Microorganisms of the gastrointestinal (GI) tract were recently shown to communicate and consequently influence the metabolism, immunity, and behavior of animal hosts. Increasing evidence suggest that communication can also occur in the opposite direction, with hormones and other host-secreted compounds being sensed by microorganisms. Here, we addressed one key aspect of the host-microbe communication by studying a very‐well known system that senses external stimulus, the chemotaxis system. We analyzed the chemotactic response of a model commensal bacterium, Escherichia coli, to several compounds that accumulate in the GI tract, namely the catecholamines 3,4-dihydroxyphenylalanine, dopamine, norepinephrine, epinephrine and 3,4-dihydroxymandelic acid; the thyroid hormones serotonin and melatonin; the sex hormones β-estradiol and testosterone; insulin; and the polyamines putrescine and spermidine. Melatonin, testosterone and spermidine were shown to be chemorepellents, with the strongest repellent response observed for spermidine, and epinephrine showed an attractant response. Biphasic responses were observed to dopamine, norepinephrine, 3,4-dihydroxymandelic acid and insulin. To determine the underlying sensing mechanism of these compounds, we investigated the chemotactic responses of strains expressing hybrid receptors that combine domains of each of the two most abundant receptors in E. coli, Tar and Tsr. We also studied the responses of mutated Tar receptors that show inverted chemotactic responses, which enable us to identify regions of receptors that sense individual compounds. While the hormones are sensed indirectly, mainly perturbing the signaling domain of Tar and Tsr, the response to spermidine involves the low-abundant chemoreceptor Trg and the periplasmic binding protein PotD, of the spermidine uptake system. Finally, to determine the physiological importance of these compounds to E. coli, we studied their effects on bacterial growth. The chemotactic effects of the tested compounds apparently correlate with their influence on growth and with their stability in the GI tract, pointing to the specificity of the observed behavior. We hypothesize that the repellent responses observed at high concentrations of chemoeffective compounds might enable bacteria to avoid harmful levels of hormones and polyamines in the gut.

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