Figure 1. Potential mutagenic effects of pks⁺ E. coli.

E. coli strains can produce harmful toxins. Top right: The polyketide synthase (pks) island encodes the genes required for the synthesis of colibactin, a well-known genotoxin. Recent studies showed that polyphosphate kinase (PPK) activity is essential for ClbB function and colibactin metabolism. The ulcerative colitis medication mesalamine reduces PPK activity and colibactin production. Bottom right: Colibactin binding to DNA forms DNA cross-links and interstrand breaks that dysregulate cell division and increase mutagenesis. Importantly, a colibactin-specific mutational signature, characterized by single-base substitutions, deletions, and insertions at T sites, is enriched in CRC. indel, insertion-deletion; del, deletion of nucleotide; ins, insertion of nucleotide.