Adrenaline modulates the global transcriptional profile of Salmonella revealing a role in the antimicrobial peptide and oxidative stress resistance responses.
BACKGROUND
The successful interaction of bacterial pathogens with host tissues requires the sensing of specific chemical and physical cues. The human gut contains a huge number of neurons involved in the secretion and sensing of a class of neuroendocrine hormones called catecholamines. Recently, in Escherichia coli O157:H7, the catecholamines adrenaline and noradrenaline were shown to act synergistically with a bacterial quorum sensing molecule, autoinducer 3 (AI-3), to affect bacterial virulence and motility. We wished to investigate the impact of adrenaline on the biology of Salmonella spp.


RESULTS
We have determined the effect of adrenaline on the transcriptome of the gut pathogen Salmonella enterica serovar Typhimurium. Addition of adrenaline led to an induction of key metal transport systems within 30 minutes of treatment. The oxidative stress responses employing manganese internalisation were also elicited. Cells lacking the key oxidative stress regulator OxyR showed reduced survival in the presence of adrenaline and complete restoration of growth upon addition of manganese. A significant reduction in the expression of the pmrHFIJKLM antimicrobial peptide resistance operon reduced the ability of Salmonella to survive polymyxin B following addition of adrenaline. Notably, both phenotypes were reversed by the addition of the beta-adrenergic blocker propranolol. Our data suggest that the BasSR two component signal transduction system is the likely adrenaline sensor mediating the antimicrobial peptide response.


CONCLUSIONS
Salmonella are able to sense adrenaline and downregulate the antimicrobial peptide resistance pmr locus through the BasSR two component signalling system. Through iron transport, adrenaline may affect the oxidative stress balance of the cell requiring OxyR for normal growth. Both adrenaline effects can be inhibited by the addition of the beta-adrenergic blocker propranolol. Adrenaline sensing may provide an environmental cue for the induction of the Salmonella stress response in anticipation of imminent host-derived oxidative stress. However, adrenaline may also serve in favour of the host defences by lowering antimicrobial peptide resistance and hence documenting for the first time such a function for a hormone.
Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle NE2 4HH, UK. michail.karavolos@ncl.ac.uk
M H
MH
Karavolos
H
H
Spencer
D M
DM
Bulmer
A
A
Thompson
K
K
Winzer
P
P
Williams
J C D
JC
Hinton
C M Anjam
CM
Khan
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology*; D009876:Operon / Q000187:drug effects; D018384:Oxidative Stress; D011112:Polymyxin B / Q000378:metabolism / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011112:Polymyxin B; D004837:Epinephrine