title: Norepinephrine augments Salmonella enterica-induced enteritis in a manner associated with increased net replication but independent of the putative adrenergic sensor kinases QseC and QseE.
abstract: Stress has long been correlated with susceptibility to microbial infection. One explanation for this phenomenon is the ability of pathogens to sense and respond to host stress-related catecholamines, such as norepinephrine (NE). In Gram-negative enteric pathogens, it has been proposed that NE may facilitate growth by mediating iron supply, or it may alter gene expression by activating adrenergic sensor kinases. The aim of this work was to investigate the relative importance of these processes in a model in which NE alters the outcome of Salmonella enterica serovar Typhimurium infection. A bovine ligated ileal loop model was used to study the effect of NE on enteritis induced by S. Typhimurium and on the bacterial in vivo replication rate. Mutants lacking putative adrenergic receptor genes were assessed in the loop model, in a calf intestinal colonization model, and in vitro. S. Typhimurium-induced enteritis was significantly enhanced by addition of 5 mM NE. This effect was associated with increased net bacterial replication in the same model. Exogenous ferric iron also stimulated bacterial replication in the medium used but not transcription of enteritis-associated loci. The putative adrenergic sensors QseC and QseE were not required for NE-enhanced enteritis, intestinal colonization of calves, or NE-dependent growth in iron-restricted medium and did not influence expression or secretion of enteritis-associated virulence factors. Our findings support a role for stress-related catecholamines in modulating the virulence of enteric bacterial pathogens in vivo but suggest that bacterial adrenergic sensors may not be the vital link in such interkingdom signaling in Salmonella.
authors.affiliation: Division of Microbiology, Institute for Animal Health, Compton, Berkshire, RG20 7NN, United Kingdom.
authors.forename: Gillian D
authors.initials: GD
authors.lastname: Pullinger
authors.forename: Sonya C
authors.initials: SC
authors.lastname: Carnell
authors.forename: Fathima F
authors.initials: FF
authors.lastname: Sharaff
authors.forename: Pauline M
authors.initials: PM
authors.lastname: van Diemen
authors.forename: Francis
authors.initials: F
authors.lastname: Dziva
authors.forename: Eirwen
authors.initials: E
authors.lastname: Morgan
authors.forename: Mark
authors.initials: M
authors.lastname: Lyte
authors.forename: Primrose P E
authors.initials: PP
authors.lastname: Freestone
authors.forename: Mark P
authors.initials: MP
authors.lastname: Stevens
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002417:Cattle; D002418:Cattle Diseases / Q000382:microbiology; D049109:Cell Proliferation / Q000187:drug effects; D004751:Enteritis / Q000382:microbiology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D019779:Salmonella enterica / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D009638:Norepinephrine