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Title:   Author  item
                                            Arsenault, Ryanitem
                                            NAPPER, SCOTT - University Of Saskatchewanitem
                                            Kogut, Michael

                                                         - *Mike*
  Submitted to: Veterinary Research
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/9/2013
                                    Publication  Date: 5/17/2013
                                    Publication URL: http://handle.nal.usda.gov.10113/58131Citation: Arsenault, R.J., Napper, S., Kogut, M.H. 2013. Salmonella enterica Typhimurium infection causes metabolic changes in chicken muscle involving AMPK, fatty acid and insulin/mTOR signaling. Veterinary Research. 4:35-49.Interpretive Summary: Salmonella enterica serovar Typhimurium (ST) infection of chickens more than a few days old does not make the animals sick but does stay in the intestinal tract and is shed in the feces, potentially infecting other animals as well as humans.  Despite ST infection not making chickens sick, we hypothesized that it was still causing potentially negative changes within the bird as a whole.  Specifically, we looked at muscle from infected and uninfected chickens to see if there were any metabolic changes occurring.  The tool we used to find these changes works by measuring the signals within a cell.  These signals depend on the addition or subtraction of a phosphate group to proteins within the cell.  We found that a protein called 5'-adenosine monophosphate-activated protein kinase (AMPK), which is central to metabolism, showed changes when comparing infected chickens to uninfected chickens.  AMPK causes changes in fat and sugar metabolism within chickens.  We also found changes in the signals normally involved with insulin, an important part of metabolism.  This study is the first to show changes in chicken phosphorylation-mediated metabolism signaling following ST infection.
                                Technical Abstract: Salmonella enterica serovar Typhimurium (ST) infection of chickens more than a few days old results in asymptomatic cecal colonization with persistent shedding of bacteria.  We hypothesized that while the bacteria colonize and persist locally in the cecum, it has systemic effects influencing the physiology of the avian host, including metabolic pathways of skeletal muscle.  Using species-specific peptide arrays to perform kinome analysis on metabolic signaling pathways in skeletal muscle of ST infected chickens, we have observed key metabolic changes that affected fatty acid and glucose metabolism through the 5'-adenosine monophosphate-activated protein kinase (AMPK) and the insulin/mammalian target of rapamycin (mTOR) signaling pathway.  Over a three week time course of infection, we observed changes in the phosphorylation state of the AMPK protein in the muscle, as well as proteins both upstream and downstream.  In addition, changes to a large subset of the protein intermediates of the insulin/mTOR pathway in the skeletal muscle were altered by infection.  Early in the infection, energy stores are mobilized through active AMPK activity, perhaps as a stress-related response.  In later stages of infection, AMPK appears to be deactivated, as does the mTOR branch of the insulin signaling pathway, though other parts of the insulin pathway remain active.  These later changes appear to be related to fatty acid anabolic and glucose catabolic processes.  These results have implications not only for animal production and health, but for the understanding of how Salmonella infection in the intestine can have widespread, systemic effects on the metabolism of chickens without disease-like symptoms.


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