Ethanolamine Signaling Promotes Salmonella Niche Recognition and Adaptation during Infection

Abstract

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.

Author Summary

Chemical signaling underlies all cellular processes. Bacteria rely on chemical signaling to gain information about the local environment and precisely regulate gene expression. Ethanolamine is an abundant molecule within mammalian hosts that plays an important role in mammalian physiology and also serves as a carbon and nitrogen source for bacteria. Here we show that the foodborne pathogen Salmonella enterica exploits ethanolamine as a signal of distinct host environments to coordinate metabolism and virulence, which enhances disease progression during infection. The ability to sense ethanolamine is conserved in diverse bacteria; thus, these studies reveal that ethanolamine signaling may be important for bacterial adaptation to the mammalian host.