Tryptic oncopeptide secreted from the gut bacterium Cronobacter malonaticus PO3 promotes colorectal cancer

The involvement of Cronobacter, which is frequently associated with meningitis and necrotizing enterocolitis, in human colorectal cancer remains unexplored. In this study, we isolate and characterize a novel strain of C. malonaticus designated PO3 from a fecal sample of a colon cancer patient and demonstrate its proliferative effects on colorectal cancer both in vitro and in vivo. The secretome of PO3 significantly promoted cell proliferation, as evidenced by increased cell viability, fluorescence intensity, and Ki-67 expression, without inducing cell death. Furthermore, using high-resolution mass spectrometry (HRMS), we identified a novel tryptic oncopeptide designated P506, in the PO3 secretome that promotes colorectal cancer. Synthetic P506 further stimulated human colorectal adenocarcinoma cell line HT-29 cell proliferation in a dose-dependent manner. Experiments with the BALB/c mouse model in vivo revealed that both the PO3 secretome and P506 contributed to the development of colorectal polyps and associated histological changes, including dysplasia and altered colonic architecture. These findings suggest that P506, a potent peptide from the PO3 secretome, may have oncogenic potential, promoting colorectal cancer progression.