New Publication: Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer

Cancer Cell; VOLUME 42, ISSUE 3, P487-496.E6, MARCH 11, 2024 

https://doi.org/10.1016/j.ccell.2024.02.009

Co-culture of intestinal organoids with a colibactin-producing pks+ E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E. coli Nissle 1917 (EcN) remains a commonly used probiotic, despite harboring the pksoperon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+ E. colistrains with an analytical framework based on sequence characteristic of colibactin-induced mutations. All strains, including EcN, display varying levels of mutagenic activity. Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ∼12% of CRC genomes and even in whole exome sequencing data, representing a crucial step toward pinpointing the mutagenic activity of distinct pks+ E. coli strains.