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An important chemical exchange within the gut involves the neurotransmitters epinephrine and\/or norepinephrine, extensively reported to increase virulence gene expression in EHEC, acting through two bacterial adrenergic sensors: QseC and QseE. However, EHEC is unable to establish itself and cause its hallmark lesions, attaching and effacing (AE) lesions, on murine enterocytes. To address the role of these neurotransmitters during enteric infection, we employed\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    . Both EHEC and\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    harbor the locus of enterocyte effacement (LEE) that is necessary for AE lesion formation. Here we show that expression of the LEE, as well as that of other virulence genes in\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    , is also activated by epinephrine and\/or norepinephrine. Both QseC and QseE are required for LEE gene activation in\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    , and the\n                    <jats:italic>qseC<\/jats:italic>\n                    and\n                    <jats:italic>qseE<\/jats:italic>\n                    mutants are attenuated for murine infection.\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    has a decreased ability to colonize dopamine \u03b2-hydroxylase knockout (Dbh\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice, which do not produce epinephrine and norepinephrine. Both adrenergic sensors are required for\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    to sense these neurotransmitters and activate the LEE genes during infection. These data indicate that epinephrine and norepinephrine are sensed by bacterial adrenergic receptors during enteric infection to promote activation of their virulence repertoire. This is the first report of the role of these neurotransmitters during mammalian gastrointestinal (GI) infection by a noninvasive pathogen.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The epinephrine and norepinephrine neurotransmitters play important roles in gut physiology and motility. Of note, epinephrine and norepinephrine play a central role in stress responses in mammals, and stress has profound effects on GI function. Bacterial enteric pathogens exploit these neurotransmitters as signals to coordinate the regulation of their virulence genes. The bacterial QseC and QseE adrenergic sensors are at the center of this regulatory cascade.\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    is a noninvasive murine pathogen with a colonization mechanism similar to that of EHEC, enabling the investigation of host signals in mice. The presence of these neurotransmitters in the gut is necessary for\n                    <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n                    to fully activate its virulence program, in a QseC\/QseE-dependent manner, to successfully colonize its murine host. Our study data provide the first example of epinephrine and norepinephrine signaling within the gut to stimulate infection by a bacterial pathogen in a natural animal infection.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00826-16","type":"journal-article","created":{"date-parts":[[2016,6,7]],"date-time":"2016-06-07T20:58:46Z","timestamp":1465333126000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":153,"title":["Bacterial Adrenergic Sensors Regulate Virulence of Enteric Pathogens in the Gut"],"prefix":"10.1128","volume":"7","author":[{"given":"Cristiano G.","family":"Moreira","sequence":"first","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"School of Pharmaceutical Sciences, State University of Sao Paulo (UNESP), Araraquara, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regan","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Animesh Anand","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine\/Pathobiology, Kansas State University, Manhattan, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences, University of Surrey, Guildford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Howard Hughes Medical Institute, Division of Infectious Diseases, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith M.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1532-9178","authenticated-orcid":false,"given":"Sebastian E.","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Weinshenker","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Sperandio","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA"},{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2011.00094"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(00)00127-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4249\/scholarpedia.7204"},{"key":"e_1_3_3_5_2","first-page":"G1367","article-title":"Segment-specific effects of epinephrine on ion transport in the colon of the rat","volume":"275","author":"H\u00f6rger S","year":"1998","unstructured":"H\u00f6rger S, Schultheiss G, Diener M. 1998. 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