title: 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.
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Anderson
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Clark
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Mazhar
authors.initials: M
authors.lastname: Adli
authors.affiliation: Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Kendall
mesh_terms: D000220:Adaptation, Biological / Q000276:immunology; D000818:Animals; D019856:Ethanolamine / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D044404:Genomic Islands / Q000276:immunology; D006801:Humans; D012481:Salmonella Infections, Animal / Q000378:metabolism* / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000472:pathogenicity; D015398:Signal Transduction; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D037521:Virulence Factors; D019856:Ethanolamine