Enteric Bacterial Regulation of the Wnt/β-Catenin Signaling

Abstract

Enteric bacteria such as Salmonella use a type three secretion system to inject bacterial pathogenic proteins, known as effectors, into host cells. These injected virulent effectors mimic the activity of eukaryotic proteins and debilitate host-cell signaling pathways. Salmonella infection is a common public health problem that can become chronic and increase the risk of cancer. In this chapter, we summarize the research progress on Salmonella regulation of Wnt/beta-catenin signaling. The Wnt/beta-catenin signaling is critical in intestinal renewal and development, inflammation, and tumorigenesis. We discuss in vitro and in vivo experimental models, especially the recently developed organoid system used for investigating Salmonella-host interactions. Finally, we highlight the novel roles of Salmonella effector protein AvrA in chronically activating Wnt/beta-catenin signaling, impacting intestinal renewal and thus promoting colitis-associated cancer. These findings indicate the importance of understanding the complex interactions between bacteria and hosts in infection, inflammation, and cancer. The established experimental models (e.g., organoids, the chronic infected mouse model, and the infected colon cancer model) can be applied to investigating other bacteria and their interactions with hosts.