Huber, A.R., Pleguezuelos-Manzano, C., Puschhof, J. et al. (14 more authors) (2024) Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer. Cancer Cell, 42 (3). 487-496.E6. ISSN 1535-6108
Abstract
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% 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | Ⓒ 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
Keywords: | cancer genomics; genotoxins; organoids; mutational signatures; colorectal cancer; colibactin; probiotics; bacteria; mutagenesis; machine learning |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Pathology and Data Analytics |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Mar 2024 16:24 |
Last Modified: | 15 Mar 2024 16:24 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ccell.2024.02.009 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:210321 |