The effect of the human gut-signalling hormone, norepinephrine, on the growth of the gastric pathogen Helicobacter pylori.
OBJECTIVE
Helicobacter pylori is an important human pathogen, infecting around half the population of the world. It has developed a number of refinements to allow it to persist in the human stomach. Catecholamine hormones have been shown to enhance growth of other bacterial species and are found in the gastric niche. We aimed to study growth enhancement of H. pylori by the human catecholamine hormones epinephrine and norepinephrine.


METHODS
Growth studies were carried out in complex and defined media containing the hormones epinephrine, norepinephrine, and normetanephrine, the main host metabolite of norepinephrine. Bacterial density was measured by viable count or optical density. Intracellular ATP was measured using a bioluminescence assay technique.


RESULTS
Both epinephrine and norepinephrine enhanced H. pylori growth in a dose-dependent strain-independent fashion, with norepinephrine being more effective than epinephrine. We showed a rapid (4 hours) dose-dependent effect on metabolic activity, as measured by intracellular ATP levels. We used a chemically defined medium to study mechanisms: chelation of ferric iron blocked H. pylori growth, which could be overcome by addition of norepinephrine. Disruption of the catechol group of norepinephrine abrogated its H. pylori-growth-promoting activity.


CONCLUSIONS
Norepinephrine stimulates growth of H. pylori under otherwise growth-restricted conditions, and this effect is related to the ability of norepinephrine to bind ferric iron. This supports the notion that norepinephrine may aid H. pylori persistence in the stomach.
Doherty
Neil C
NC
Institute of Infections, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
Tobias
Amanda
A
Watson
Sue
S
Atherton
John C
JC
D000255:Adenosine Triphosphate / Q000032:analysis; D018533:Biomass; D015169:Colony Count, Microbial; D003470:Culture Media / Q000737:chemistry; D003600:Cytosol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism; D016480:Helicobacter pylori / Q000254:growth & development*; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000378:metabolism
D003470:Culture Media; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D009647:Normetanephrine; D000255:Adenosine Triphosphate; D009638:Norepinephrine; D004837:Epinephrine