Consistent activation of the β-catenin pathway by Salmonella type-three secretion effector protein AvrA in chronically infected intestine.

Abstract

Salmonella infection is a common public health problem that can become chronic and increase the risk of cancer. Live, mutated Salmonella is used to target cancer cells. However, few studies have addressed chronic Salmonella infection in vivo. AvrA is a Salmonella type-three secretion effector that is multifunctional, inhibiting intestinal inflammation and enhancing proliferation. β-catenin is a key player in intestinal renewal, inflammation, and tumorigenesis. We hypothesize that in Salmonella-infected intestine, AvrA chronically activates the β-catenin pathway and increases cell proliferation, thus deregulating the intestinal responses to bacterial infection. We followed mice with Salmonella infection for 27 wk and investigated the physiological effects and role of AvrA on β-catenin in chronically infected intestine. We found that AvrA persistently regulated β-catenin posttranslational modifications, including phosphorylation and acetylation. Moreover, the upstream regulator Akt, transcription factors, T cell factors, nuclear β-catenin, and β-catenin target genes were enhanced in mice infected with Salmonella-expressing AvrA. AvrA has a chronic functional role in promoting intestinal renewal. In summary, we have uncovered an essential role of Salmonella AvrA in chronically activating β-catenin and impacting intestinal renewal in small intestine and colon. Our study emphasizes the importance of AvrA in chronic bacterial infection.

• Authors: Rong Lu, Xingyin Liu, Shaoping Wu, Yinglin Xia, Yong-Guo Zhang, Elaine O Petrof, Erika C Claud, Jun Sun
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 303 Issue 10 Pg. G1113-25 (Nov 15 2012) ISSN: 1522-1547 [Electronic] United States
• PMID: 22982337 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AvrA protein, Salmonella typhimurium
• Bacterial Proteins
• beta Catenin

Topics

• Animals
• Bacterial Proteins (pharmacology, physiology)
• Cecum (microbiology)
• Cell Proliferation (drug effects)
• Epithelial Cells (physiology)
• Mice
• Salmonella Infections, Animal (physiopathology)
• beta Catenin (metabolism)