Salmonella typhimurium infection increases p53 acetylation in intestinal epithelial cells.
The ability of Salmonella typhimurium to enter intestinal epithelial cells constitutes a crucial step in pathogenesis. Salmonella invasion of the intestinal epithelium requires bacterial type three secretion system. Type three secretion system is a transport device that injects virulence proteins, called effectors, to paralyze or reprogram the eukaryotic cells. Avirulence factor for Salmonella (AvrA) is a Salmonella effector that inhibits the host's inflammatory responses. The mechanism by which AvrA modulates host cell signaling is not entirely clear. p53 is situated at the crossroads of a network of signaling pathways that are essential for genotoxic and nongenotoxic stress responses. We hypothesized that Salmonella infection activates the p53 pathway. We demonstrated that Salmonella infection increased p53 acetylation. Cells infected with AvrA-sufficient Salmonella have increased p53 acetylation, whereas cells infected with AvrA-deficient Salmonella have less p53 acetylation. In a cell-free system, AvrA possessed acetyltransferase activity and used p53 as a substrate. AvrA expression increased p53 transcriptional activity and induced cell cycle arrest. HCT116 p53-/- cells had less inflammatory responses. In a mouse model of Salmonella infection, intestinal epithelial p53 acetylation was increased by AvrA expression. Our studies provide novel mechanistic evidence that Salmonella modulates the p53 pathway during intestinal inflammation and infection.
Dept. of Medicine, University of Rochester, NY, USA.
Shaoping
S
Wu
Zhongde
Z
Ye
Xingyin
X
Liu
Yun
Y
Zhao
Yinglin
Y
Xia
Andrew
A
Steiner
Elaine O
EO
Petrof
Erika C
EC
Claud
Jun
J
Sun
D000107:Acetylation; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D012480:Salmonella Infections / Q000503:physiopathology*; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C487891:AvrA protein, Salmonella typhimurium; D001426:Bacterial Proteins; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53