Date Published: November 13, 2015
Publisher: Public Library of Science
Author(s): Christopher J. Anderson, David E. Clark, Mazhar Adli, Melissa M. Kendall, Andreas J Baumler.
Chemical and nutrient signaling are fundamental for all cellular processes, including interactions between the mammalian host and the microbiota, which have a significant impact on health and disease. Ethanolamine is an essential component of cell membranes and has profound signaling activity within mammalian cells by modulating inflammatory responses and intestinal physiology. Here, we describe a virulence-regulating pathway in which the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits ethanolamine signaling to recognize and adapt to distinct niches within the host. The bacterial transcription factor EutR promotes ethanolamine metabolism in the intestine, which enables S. Typhimurium to establish infection. Subsequently, EutR directly activates expression of the Salmonella pathogenicity island 2 in the intramacrophage environment, and thus augments intramacrophage survival. Moreover, EutR is critical for robust dissemination during mammalian infection. Our findings reveal that S. Typhimurium co-opts ethanolamine as a signal to coordinate metabolism and then virulence. Because the ability to sense ethanolamine is a conserved trait among pathogenic and commensal bacteria, our work indicates that ethanolamine signaling may be a key step in the localized adaptation of bacteria within their mammalian hosts.
Chemical and nutrient signaling mediate diverse biological processes, and underlie interactions among the mammalian host, the resident microbiota, and invading pathogens . Ethanolamine is abundant in cell membranes, as a component of phosphatidylethanolamine as well as in modified lipid molecules such as N-acylethanolamines . These ethanolamine-containing compounds play important roles in mammalian cell signaling and influence diverse physiological effects, including cytokinesis, immunomodulation, food intake and energy balance [2–4]. Ethanolamine is abundant in the intestinal tract due to the turnover and exfoliation of enterocytes and bacterial cells [5,6], and intracellular pools of ethanolamine are maintained by low and high affinity uptake systems as well as through internal recycling of phosphatidylethanolamine [7–10].