%0 Journal Article
%A Rosendahl Huber, Axel
%A Pleguezuelos-Manzano, Cayetano
%A Puschhof, Jens
%A Ubels, Joske
%A Boot, Charelle
%A Saftien, Aurelia
%A Verheul, Mark
%A Trabut, Laurianne T
%A Groenen, Niels
%A van Roosmalen, Markus
%A Ouyang, Kyanna S
%A Wood, Henry
%A Quirke, Phil
%A Meijer, Gerrit
%A Cuppen, Edwin
%A Clevers, Hans
%A van Boxtel, Ruben
%T Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer.
%J Cancer cell
%V 42
%N 3
%@ 1535-6108
%C New York, NY
%I Elsevier
%M DKFZ-2024-00523
%P 487 - 496.e6
%D 2024
%X 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 pks operon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+E. coli strains 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
%K bacteria (Other)
%K cancer genomics (Other)
%K colibactin (Other)
%K colorectal cancer (Other)
%K genotoxins (Other)
%K machine learning (Other)
%K mutagenesis (Other)
%K mutational signatures (Other)
%K organoids (Other)
%K probiotics (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38471458
%R 10.1016/j.ccell.2024.02.009
%U https://inrepo02.dkfz.de/record/288881