The role of p53 and its isoforms in spontaneous bacterial peritonitis

Introduction Spontaneous Bacterial Peritonitis (SBP) is a life-threatening complication of liver cirrhosis. In liver cirrhosis patients, a thinner mucus facilitates direct contact between bacteria and intestinal epithelial cells, resulting in the degradation of cell-cell contact proteins (Occludin and E-Cadherin). This leads to tissue damage and cellular stress (Haderer et al. Gut 2023). We investigate the association between tissue damage-induced cellular stress and p53 with a special focus on the induction of different p53 isoforms.

Methods To assess p53 isoform expression, we employed an exon-specific isoform expression reporter system (EXSISERS) integrated into exon 2, 4, and 7 of TP53 allowing us to distinguish three major isoform groups (anti-tumorigenic full-length p53 and Δ40p53 as well as oncogenic Δ133p53) in HCT116 colorectal cancer cells. Cells were co-cultured with the laboratory E.coli strain O6:Hnt, and the SBP patient-derived strains Ont:H7, and Ont:H41. p53 Isoform expression was evaluated.

Results Co-incubation with laboratory E.coli at an MOI of 5 resulted in the early upregulation of △40p53 expression within 15 minutes. Full-length p53 was induced after 4 hours. Simultaneously, we observed a gradual reduction in △133p53, known for its anti-apoptotic and pro-oncogenic properties. Thus, isoforms inducing cell death or cell cycle arrest were induced, and oncogenic isoforms were found to be downregulated.

Conclusion E.coli induce cellular stress by induction of tissue damage resulting in upregulation of pro-apoptotic p53 isoforms. These isoforms trigger cell cycle arrest and cell death. Cell cycle arrest helps cells adapt to bacterial stress, while increased cell death removes damaged cells.

Publication History

Article published online:
23 January 2024