TY  - JOUR
AU  - Rosendahl Huber, Axel
AU  - Pleguezuelos-Manzano, Cayetano
AU  - Puschhof, Jens
AU  - Ubels, Joske
AU  - Boot, Charelle
AU  - Saftien, Aurelia
AU  - Verheul, Mark
AU  - Trabut, Laurianne T
AU  - Groenen, Niels
AU  - van Roosmalen, Markus
AU  - Ouyang, Kyanna S
AU  - Wood, Henry
AU  - Quirke, Phil
AU  - Meijer, Gerrit
AU  - Cuppen, Edwin
AU  - Clevers, Hans
AU  - van Boxtel, Ruben
TI  - Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer.
JO  - Cancer cell
VL  - 42
IS  - 3
SN  - 1535-6108
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-00523
SP  - 487 - 496.e6
PY  - 2024
AB  - 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
KW  - bacteria (Other)
KW  - cancer genomics (Other)
KW  - colibactin (Other)
KW  - colorectal cancer (Other)
KW  - genotoxins (Other)
KW  - machine learning (Other)
KW  - mutagenesis (Other)
KW  - mutational signatures (Other)
KW  - organoids (Other)
KW  - probiotics (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:38471458
DO  - DOI:10.1016/j.ccell.2024.02.009
UR  - https://inrepo02.dkfz.de/record/288881
ER  -