Investigating spontaneous bacterial peritonitis – a novel role of the p53 family in bacteria-host-interaction

Background Spontaneous bacterial peritonitis (SBP) – a severe complication of liver cirrhosis - is driven by bacterial translocation. Although it is known that bacterial translocation is promoted by immune dysfunctions, increased intestinal permeability and bacterial overgrowth in patients with liver cirrhosis, the detailed mechanism of SBP development is still unknown. With wide-ranging function in immunity and cellular stress response, involvement of the p53 family in liver cirrhosis and SBP is conceivable. Therefore, we studied the regulation of p53 family members and their target function in an intestinal in vitro model.

Methods To study intestinal bacteria-host-interaction, we established an intestinal in vitro model with HCT-116 epithelial cell line. To mimic bacterial overgrowth, HCT-116 cells were cocultured with Escherichia coli (E. coli) at different concentrations for up to 4 hours. Regulation of p53 and p73 were studied via qPCR and Western blot. Additionally, p53 family target functions were analyzed via cell death induction upon bacterial stimulation. Using heat inactivation, ultrasonification and filtration, we determined whether contact with viable and intact bacteria is necessary to induce cell death.

Results Coincubation of HCT-116 cells with E. coli resulted in a decrease of p53 and p73 protein levels in a time- and dose-dependent manner. Despite reduced levels of p53 family members, a high rate of cell death after E. coli stimulation was observed, although apoptosis as an underlying mode of cell death could be excluded. It was further shown that direct contact with viable bacteria was necessary to induce cell death in this in vitro model.

Conclusion Bacterial overgrowth as in advanced liver cirrhosis is accompanied with reduced intestinal expression of p53 family members. These reductions are triggered by direct contact with viable bacteria. Thus, this mechanism might contribute to prolonged bacterial replication and SBP development. To antagonize a high bacterial burden, intestinal epithelial cells induce caspase-independent cell death. In summary, these data point out to a new role of p53 regulation in bacterial infection like SBP.

Publication History

Article published online:
04 January 2021