Figure 3.

The pleiotropic effects of mesalamine on the host and on pks⁺ E. coli. Mesalamine has effects on both host cells and pks⁺ E. coli. Mesalamine inhibits the growth and enhances the death of CRC cells; mesalamine interferes with the activation of nuclear factor kappa B (NF-κB) which plays an important role for the transition from inflammation to malignancy; and, mesalamine-driven PPAR-γ activation restores mitochondrial bioenergetics that consume O₂, and thereby restore epithelial hypoxia. Mesalamine limits the expansion of pks⁺ E. coli by reducing epithelial oxygenation or directly inhibiting the aerobic growth. Mesalamine is an inhibitor of polyphosphate kinase (PPK), by which mesalamine may inhibit various of bacterial abilities, such as persistence, biofilm formation and interference with immune cells; and mesalamine inhibits colibactin production in a PPK-dependent and independent way.