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Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells
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Escherichia coli is a normal inhabitant of the human gut. However, E. coli strains of phylogenetic group B2 harbor a genomic island called “ pks ” that codes for the production of a polyketide-peptide genotoxin, Colibactin. Here we report that in vivo infection with E. coli harboring the pks island, but not with a pks isogenic mutant, induced the formation of phosphorylated H2AX foci in mouse enterocytes. We show that a single, short exposure of cultured mammalian epithelial cells to live pks + E. coli at low infectious doses induced a transient DNA damage response followed by cell division with signs of incomplete DNA repair, leading to anaphase bridges and chromosome aberrations. Micronuclei, aneuploidy, ring chromosomes, and anaphase bridges persisted in dividing cells up to 21 d after infection, indicating occurrence of breakage–fusion–bridge cycles and chromosomal instability. Exposed cells exhibited a significant increase in gene mutation frequency and anchorage-independent colony formation, demonstrating the infection mutagenic and transforming potential. Therefore, colon colonization with these E. coli strains harboring the pks island could contribute to the development of sporadic colorectal cancer.
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“Accordingly, we observed that pksC E. coli infection, which is known to induce DNA damage, 9,10 induced c-Myc expression and its binding to the miR-20a-5p promoter.”
From The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment (2014) · cites this paper as [10]
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Metadata
- Authors
- Cuevas-Ramos, G., Petit, C. R., Marcq, I., Boury, M., Oswald, E., & Nougayrède, J.-P.
- Affiliations
- Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1225, F-31076 Toulouse, France;
- École Nationale Vétérinaire de Toulouse (FR)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-06-07
- Volume
- 107
- Issue
- 25
- Pages
- 11537-11542
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2895108
- OpenAlex
- W2026897048
- Cited by
- 855
- References
- 36
- Citations by year
- 2026: 51 · 2025: 67 · 2024: 82 · 2023: 72 · 2022: 62 · 2021: 94 · 2020: 87 · 2019: 55 · 2018: 54 · 2017: 45 · 2016: 40 · 2015: 43 · 2014: 39 · 2013: 35 · 2012: 19
- FWCI
- 6.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- Escherichia coli, colibactin, DNA damage response, enterocytes, genomic instability, chromosomal instability, anaphase bridges, micronuclei, aneuploidy, ring chromosomes, bacterial genotoxins, colorectal cancer, intestinal colonization, bacterial transformation, gene mutation frequency
- MeSH terms
- Animals, Cell Adhesion, Chromosome Aberrations, Cricetulus, DNA Damage, DNA Repair, Escherichia coli, Cricetinae, Intestines, Mice, Inbred BALB C, Mutagens, Mutation, Neoplasms, CHO Cells, Genomic Instability, Mice
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