Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells

Cuevas-Ramos, Gabriel; Petit, Claude R.; Marcq, Ingrid; Boury, Michèle; Oswald, Eric; Nougayrède, Jean-Philippe

doi:10.1073/pnas.1001261107

Cited by 855Carcinogens and Genotoxicity AssessmentEscherichia coli research studiesGenetic factors in colorectal cancer

Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells

Open access

Cuevas-Ramos, Gabriel, Petit, Claude R., Marcq, Ingrid, Boury, Michèle, Oswald, Eric, Nougayrède, Jean-Philippe·2010·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1001261107PMC PMC2895108

Open this paper in CoChat — free account

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1073/pnas.1001261107

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

pksC E. coli infection induced c-Myc expression and its binding to the miR-20a-5p promoter.
“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]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Diversity of the Human Intestinal Microbial Flora
Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., & Relman, D. A. (2005) · Science · doi:10.1126/science.1110591 · Cited by 7,913 · see citing works
DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438 · see citing works
Metagenomic Analysis of the Human Distal Gut Microbiome
Gill, S. R., Pop, M., DeBoy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S., Gordon, J. I., Relman, D. A., Fraser-Liggett, C. M., & Nelson, K. E. (2006) · Science · doi:10.1126/science.1124234 · Cited by 4,699 · see citing works
Cytokinesis-block micronucleus cytome assay
Fenech, M. F. (2007) · Nature Protocols · doi:10.1038/nprot.2007.77 · Cited by 2,025 · see citing works
Genetic instability in colorectal cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1997) · Nature · doi:10.1038/386623a0 · Cited by 1,995 · see citing works
Microbes in Gastrointestinal Health and Disease
Neish, A. S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.10.080 · Cited by 1,388 · see citing works
Escherichia coli Induces DNA Double-Strand Breaks in Eukaryotic Cells
Nougayrède, J.-P., Homburg, S., Taieb, F., Boury, M., Brzuszkiewicz, E., Gottschalk, G., Buchrieser, C., Hacker, J., Dobrindt, U., & Oswald, E. (2006) · Science · doi:10.1126/science.1127059 · Cited by 1,188 · see citing works
Self-citation
Genomic and Epigenetic Instability in Colorectal Cancer Pathogenesis
Grady, W. M., & Carethers, J. M. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.07.076 · Cited by 955 · see citing works
Comparative metagenomics revealed commonly enriched gene sets in human gut microbiomes
Kurokawa, K., Itoh, T., Kuwahara, T., Oshima, K., Toh, H., Toyoda, A., Takami, H., Morita, H., Sharma, V. K., Srivastava, T. P., et al. (2007) · DNA Research · doi:10.1093/dnares/dsm018 · Cited by 869 · see citing works
Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro.
Shin, S. I., Freedman, V. H., Risser, R., & Pollack, R. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.11.4435 · Cited by 738 · see citing works
Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination
Taccioli, G. E., Gottlieb, T. M., Blunt, T., Priestley, A., Demengeot, J., Mizuta, R., Lehmann, A. R., Alt, F. W., Jackson, S. P., & Jeggo, P. A. (1994) · Science · doi:10.1126/science.8073286 · Cited by 638 · see citing works
The impact of a negligent G2/M checkpoint on genomic instability and cancer induction
Löbrich, M., & Jeggo, P. A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2248 · Cited by 627 · see citing works
A Bacterial Toxin That Controls Cell Cycle Progression as a Deoxyribonuclease I-Like Protein
Lara-Tejero, M., & Galán, J. E. (2000) · Science · doi:10.1126/science.290.5490.354 · Cited by 551 · see citing works
Examining the link between chromosomal instability and aneuploidy in human cells
Thompson, S. L., & Compton, D. A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200712029 · Cited by 521 · see citing works
Bacterial genetics by flow cytometry: rapid isolation of Salmonella typhimurium acid‐inducible promoters by differential fluorescence induction
Valdivia, R. H., & Falkow, S. (1996) · Molecular Microbiology · doi:10.1046/j.1365-2958.1996.00120.x · Cited by 486 · see citing works
Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity
Gisselsson, D., Pettersson, L., Höglund, M., Heidenblad, M., Gorunova, L., Wiegant, J. C. A. G., Mertens, F., Cin, P. D., Mitelman, F., & Mandahl, N. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090013497 · Cited by 438 · see citing works
Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines
Shi, Q., & King, R. W. (2005) · Nature · doi:10.1038/nature03958 · Cited by 396 · see citing works
Genetic Structure and Distribution of the Colibactin Genomic Island among Members of the Family Enterobacteriaceae
Putze, J., Hennequin, C., Nougayrède, J., Zhang, W., Homburg, S., Karch, H., Bringer, M.-A., Fayolle, C., Carniel, É., Rabsch, W., et al. (2009) · Infection and Immunity · doi:10.1128/iai.00522-09 · Cited by 324 · see citing works
Self-citation
Chromosome breakage after G2 checkpoint release
Deckbar, D., Birraux, J., Krempler, A., Tchouandong, L., Beucher, A., Walker, S., Stiff, T., Jeggo, P., & Löbrich, M. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200612047 · Cited by 252 · see citing works
Extracellular Superoxide Production by Enterococcus faecalis Promotes Chromosomal Instability in Mammalian Cells
Wang, X., & Huycke, M. M. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.11.040 · Cited by 243 · see citing works
Large-Scale Population Structure of Human Commensal Escherichia coli Isolates
Escobar‐Páramo, P., Grenet, K., Menach, A. L., Rode, L., Salgado, E., Amorin, C., Gouriou, S., Picard, B., Rahimy, M. C., Andremont, A., et al. (2004) · Applied and Environmental Microbiology · doi:10.1128/aem.70.9.5698-5700.2004 · Cited by 243 · see citing works
Molecular Epidemiology and Phylogenetic Distribution of the Escherichia coli pks Genomic Island
Johnson, J. R., Johnston, B., Kuskowski, M. A., Nougayrède, J., & Oswald, É. (2008) · Journal of Clinical Microbiology · doi:10.1128/jcm.00949-08 · Cited by 195 · see citing works
Self-citation
Escherichia coliStrains Belonging to Phylogenetic Group B2 Have Superior Capacity to Persist in the Intestinal Microflora of Infants
Nowrouzian, F. L., Wold, A. E., & Adlerberth, I. (2005) · The Journal of Infectious Diseases · doi:10.1086/427996 · Cited by 189 · see citing works
Structural and numerical chromosome changes in colon cancer develop through telomere-mediated anaphase bridges, not through mitotic multipolarity
Stewénius, Y., Gorunova, L., Jonson, T., Larsson, N., Höglund, M., Mandahl, N., Mertens, F., Mitelman, F., & Gisselsson, D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408454102 · Cited by 183 · see citing works
Adaptation to the Ionizing Radiation–Induced G2 Checkpoint Occurs in Human Cells and Depends on Checkpoint Kinase 1 and Polo-like Kinase 1 Kinases
Syljuåsen, R. G., Jensen, S., Bártek, J., & Lukas, J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-2144 · Cited by 168 · see citing works
Bacterial toxins and cancer — a case to answer?
Lax, A. J. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1130 · Cited by 145 · see citing works
Sporadic colorectal cancer – role of the commensal microbiota
Hope, M. E., Hold, G. L., Kain, R., & El-Omar, E. M. (2005) · FEMS Microbiology Letters · doi:10.1016/j.femsle.2005.01.029 · Cited by 109 · see citing works
An Imperfect G 2 M Checkpoint Contributes to Chromosome Instability Following Irradiation of S and G 2 Phase Cells
Krempler, A., Deckbar, D., Jeggo, P. A., & Lobrich, M. (2007) · Cell Cycle · doi:10.4161/cc.6.14.4480 · Cited by 109 · see citing works
Cigarette smoke induces anaphase bridges and genomic imbalances in normal cells
Luo, L., Werner, K. M., Gollin, S. M., & Saunders, W. S. (2004) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.06.031 · Cited by 76 · see citing works
Phosphorylated Histone H2AX Foci Persist on Rejoined Mitotic Chromosomes in Normal Human Diploid Cells Exposed to Ionizing Radiation
Suzuki, M., Suzuki, K., Kodama, S., & Watanabe, M. (2006) · Radiation Research · doi:10.1667/rr3508.1 · Cited by 72 · see citing works
DNA repair pathways involved in anaphase bridge formation
Açılan, C., Potter, D. M., & Saunders, W. S. (2007) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20425 · Cited by 66 · see citing works
THE ASSOCIATION OF MUTANTS WITH HOMOZYGOUS DEFICIENCIES IN ZEA MAYS
McClintock, B. (1941) · Genetics · doi:10.1093/genetics/26.5.542 · Cited by 60 · see citing works
Primary and Secondary Prevention in Colorectal Cancer
Vainio, H., & Miller, A. B. (2003) · Acta Oncologica · doi:10.1080/02841860310010673 · Cited by 46 · see citing works
Detection of numerical chromosomal aberrations by flow cytometry: A novel process for identifying aneugenic agents
Muehlbauer, P. A., & Schuler, M. J. (2005) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2005.05.002 · Cited by 38 · see citing works
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces genetic changes in murine intestinal tumours and cells with ApcMin mutation
Andreassen, Å. K., Vikse, R., Mikalsen, A., Adamović, T., Steffensen, I.-L., Hjertholm, H., Levan, G., & Alexander, J. (2006) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2006.01.004 · Cited by 16 · see citing works
Sporadic Colorectal Cancer: An Infectious Disease?
Sinicrope, F. A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.01.012 · Cited by 11 · see citing works

Flagged first, then by citations

Research works printed but not linked: 1

[36]Arlett CF, et al. In: Statistical Evaluation of Mutagenenicity Test Data. Kirkland DJ, editor. Cambridge, UK: Cambridge Univ. Press; 2008. pp. 66–101. [Google Scholar]

Sorted by citations

The gut microbiota, bacterial metabolites and colorectal cancer
Louis, P., Hold, G. L., & Flint, H. J. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3344 · Cited by 2,836 · see citing works
Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/β-Catenin Signaling via its FadA Adhesin
Rubinstein, M. R., Wang, X., Liu, W., Hao, Y., Cai, G., & Han, Y. W. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.07.012 · Cited by 2,476 · see citing works
Intestinal inflammation targets cancer-inducing activity of the microbiota
Arthur, J. C., Perez-Chanona, E., Mühlbauer, M., Tomkovich, S., Uronis, J. M., Fan, T.-J., Campbell, B. J., Abujamel, T., Dogan, B., Rogers, A. B., et al. (2012) · Science · doi:10.1126/science.1224820 · Cited by 2,263 · see citing works
The keystone-pathogen hypothesis
Hajishengallis, G., Darveau, R. P., & Curtis, M. A. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2873 · Cited by 1,790 · see citing works
The microbiome and cancer
Schwabe, R. F., & Jobin, C. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3610 · Cited by 1,689 · see citing works
Potential of fecal microbiota for early-stage detection of colorectal cancer
Zeller, G., Tap, J., Voigt, A. Y., Sunagawa, S., Kultima, J. R., Costea, P. I., Amiot, A., Böhm, J., Brunetti, F., Habermann, N., et al. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145645 · Cited by 1,375 · see citing works
Gut microbiota in colorectal cancer: mechanisms of action and clinical applications
Wong, S. H., & Yu, J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0209-8 · Cited by 1,355 · see citing works
Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer
Yu, J. Q., Feng, Q., Wong, S. H., Zhang, D., Liang, Q. Y., Qin, Y., Tang, L., Zhao, H., Stenvang, J., Li, Y., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309800 · Cited by 1,259 · see citing works
A bacterial driver–passenger model for colorectal cancer: beyond the usual suspects
Tjalsma, H., Boleij, A., Marchesi, J. R., & Dutilh, B. E. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2819 · Cited by 903 · see citing works
The Human Microbiota in Health and Disease
Wang, B., Yao, M., Lv, L., Ling, Z., & Li, L. (2017) · Engineering · doi:10.1016/j.eng.2017.01.008 · Cited by 861 · see citing works
Gut microbiota imbalance and colorectal cancer
Gagnière, J. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i2.501 · Cited by 856 · see citing works
Microbes, Microbiota, and Colon Cancer
Sears, C. L., & Garrett, W. S. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.007 · Cited by 820 · see citing works
The Intestinal Microbiota in Colorectal Cancer.
Tilg, H., Adolph, T. E., Gerner, R. R., & Moschen, A. R. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.004 · Cited by 777 · see citing works
Mechanisms and consequences of intestinal dysbiosis
Weiss, G. A., & Hennet, T. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2509-x · Cited by 775 · see citing works
Small molecules from the human microbiota
Donia, M. S., & Fischbach, M. A. (2015) · Science · doi:10.1126/science.1254766 · Cited by 760 · see citing works
Gut microbiota in colorectal cancer development and therapy
Wong, C. C., & Yu, J. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00766-x · Cited by 747 · see citing works
Cold and hot tumors: from molecular mechanisms to targeted therapy
Wu, B., Zhang, B., Li, B., Wu, H., & Jiang, M. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01979-x · Cited by 747 · see citing works
Gut mucosal microbiome across stages of colorectal carcinogenesis
Nakatsu, G., Li, X., Zhou, H., Sheng, J., Wong, S. H., Wu, W. K. K., Ng, S. C., Tsoi, H., Dong, Y., Zhang, N., et al. (2015) · Nature Communications · doi:10.1038/ncomms9727 · Cited by 701 · see citing works
Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in Germ-Free and Conventional Mice
Wong, S. H., Zhao, L., Zhang, X., Nakatsu, G., Han, J., Xu, W., Xiao, X., Kwong, T. N. Y., Tsoi, H., Wu, W. K. K., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.08.022 · Cited by 634 · see citing works
The Human Gut Bacterial Genotoxin Colibactin Alkylates DNA
Wilson, M. R., Jiang, Y., Villalta, P. W., Stornetta, A., Boudreau, P. D., Carrá, A., Brennan, C. A., Chun, E., Ngo, L., Samson, L. D., et al. (2019) · Science · doi:10.1126/science.aar7785 · Cited by 635 · see citing works
Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease
Jiang, W., Wu, N., Wang, X., Chi, Y., Zhang, Y., Qiu, X., Hu, Y. C., Li, J., & Liu, Y. (2015) · Scientific Reports · doi:10.1038/srep08096 · Cited by 650 · see citing works
The Microbiota of Breast Tissue and Its Association with Breast Cancer
Urbaniak, C., Gloor, G. B., Brackstone, M., Scott, L., Tangney, M., & Reid, G. (2016) · Applied and Environmental Microbiology · doi:10.1128/aem.01235-16 · Cited by 625 · see citing works
The Intestinal Microbiota and Colorectal Cancer
Cheng, Y., Ling, Z., & Li, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.615056 · Cited by 587 · see citing works
Gut Microbiota, Inflammation, and Colorectal Cancer
Brennan, C. A., & Garrett, W. S. (2016) · Annual Review of Microbiology · doi:10.1146/annurev-micro-102215-095513 · Cited by 572 · see citing works
Towards the Human Colorectal Cancer Microbiome
Marchesi, J. R., Dutilh, B. E., Hall, N., Peters, W. H. M., Roelofs, R., Boleij, A., & Tjalsma, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020447 · Cited by 552 · see citing works
Microbiota disbiosis is associated with colorectal cancer
Gao, Z., Guo, B., Gao, R., Zhu, Q., & Qin, H. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00020 · Cited by 537 · see citing works
High Prevalence of Mucosa-Associated E. coli Producing Cyclomodulin and Genotoxin in Colon Cancer
Buc, E., Dubois, D., Sauvanet, P., Raisch, J., Delmas, J., Darfeuille-Michaud, A., Pezet, D., & Bonnet, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056964 · Cited by 535 · see citing works
Targeting the gut and tumor microbiota in cancer
Park, E. M., Chelvanambi, M., Bhutiani, N., Kroemer, G., Zitvogel, L., & Wargo, J. A. (2022) · Nature Medicine · doi:10.1038/s41591-022-01779-2 · Cited by 496 · see citing works
Inflammatory networks underlying colorectal cancer
Lasry, A., Zinger, A., & Ben‐Neriah, Y. (2016) · Nature Immunology · doi:10.1038/ni.3384 · Cited by 488 · see citing works
Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype
Cougnoux, A., Dalmasso, G., Martinez, R., Buc, E., Delmas, J., Gibold, L., Sauvanet, P., Darcha, C., Déchelotte, P., Bonnet, M., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-305257 · Cited by 486 · see citing works
Colonization of the Human Gut by E. coli and Colorectal Cancer Risk
Bonnet, M., Buc, E., Sauvanet, P., Darcha, C., Dubois, D., Pereira, B., Déchelotte, P., Bonnet, R., Pezet, D., & Darfeuille-Michaud, A. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1343 · Cited by 475 · see citing works
Human Gut Microbiota and Gastrointestinal Cancer
Meng, C., Bai, C., Brown, T. D., Hood, L., & Tian, Q. (2018) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2017.06.002 · Cited by 472 · see citing works
Inflammation-induced DNA damage, mutations and cancer
Kay, J. E., Thadhani, E., Samson, L. D., & Engelward, B. P. (2019) · DNA repair · doi:10.1016/j.dnarep.2019.102673 · Cited by 479 · see citing works
Host–microbiota maladaptation in colorectal cancer
Janney, A., Powrie, F., & Mann, E. H. (2020) · Nature · doi:10.1038/s41586-020-2729-3 · Cited by 445 · see citing works
Lung microbiome: new insights into the pathogenesis of respiratory diseases
Li, R., Li, J., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01722-y · Cited by 466 · see citing works
Peptostreptococcus anaerobius Induces Intracellular Cholesterol Biosynthesis in Colon Cells to Induce Proliferation and Causes Dysplasia in Mice
Tsoi, H., Chu, E. S., Zhang, X., Sheng, J., Nakatsu, G., Ng, S. C., Chan, A. W. H., Chan, F. K. L., Sung, J. J. �., & Yu, J. Q. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.009 · Cited by 437 · see citing works
Alterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes
Nakatsu, G., Zhou, H., Wu, W. K. K., Wong, S. H., Coker, O. O., Dai, Z., Li, X., Szeto, C.-H., Sugimura, N., Lam, T. Y.-T., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.04.018 · Cited by 386 · see citing works
Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer
Arthur, J. C., Gharaibeh, R. Z., Mühlbauer, M., Perez-Chanona, E., Uronis, J. M., McCafferty, J., Fodor, A. A., & Jobin, C. (2014) · Nature Communications · doi:10.1038/ncomms5724 · Cited by 392 · see citing works
Fast food fever: reviewing the impacts of the Western diet on immunity
Myles, I. A. (2014) · Nutrition Journal · doi:10.1186/1475-2891-13-61 · Cited by 390 · see citing works
Mapping the Evolution of Hypervirulent Klebsiella pneumoniae
Struve, C., Roe, C. C., Stegger, M., Stahlhut, S. G., Hansen, D. S., Engelthaler, D. M., Andersen, P. S., Driebe, E. M., Keim, P., & Krogfelt, K. A. (2015) · mBio · doi:10.1128/mbio.00630-15 · Cited by 367 · see citing works
The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life
Beld, J., Sonnenschein, E. C., Vickery, C. R., Noel, J. P., & Burkart, M. D. (2013) · Natural Product Reports · doi:10.1039/c3np70054b · Cited by 360 · see citing works
Bacteria in cancer initiation, promotion and progression
Tekle, G. E., & Garrett, W. S. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00594-2 · Cited by 349 · see citing works
The Multifaceted Role of the Intestinal Microbiota in Colon Cancer
Irrazábal, T., Belcheva, A., Girardin, S. E., Martín, A., & Philpott, D. J. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.039 · Cited by 345 · see citing works
Gastrointestinal Malignancy and the Microbiome
Abreu, M. T., & Peek, R. M. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.01.001 · Cited by 323 · see citing works
Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota
Peterson, C. T., Sharma, V., Elmén, L., & Peterson, S. N. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12474 · Cited by 317 · see citing works
Microbiota, Inflammation and Colorectal Cancer
Lucas, C., Barnich, N., & Nguyen, H. T. T. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061310 · Cited by 318 · see citing works
The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment
Dalmasso, G., Cougnoux, A., Delmas, J., Darfeuille-Michaud, A., & Bonnet, R. (2014) · Gut Microbes · doi:10.4161/19490976.2014.969989 · Cited by 296 · see citing works
The association of diet, gut microbiota and colorectal cancer: what we eat may imply what we get
Yang, J., & Yu, J. Q. (2018) · Protein & Cell · doi:10.1007/s13238-018-0543-6 · Cited by 280 · see citing works
Microbiome, inflammation and colorectal cancer
Chen, J., Pitmon, E., & Wang, K. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.09.006 · Cited by 267 · see citing works
The Colibactin Genotoxin Generates DNA Interstrand Cross-Links in Infected Cells
Bossuet‐Greif, N., Vignard, J., Taieb, F. E., Mirey, G., Dubois, D., Petit, C. R., Oswald, É., & Nougayrède, J. (2018) · mBio · doi:10.1128/mbio.02393-17 · Cited by 260 · see citing works
Self-citation
Potential Role of the Gut Microbiome In Colorectal Cancer Progression
Kim, J.-H., & Lee, H. K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.807648 · Cited by 269 · see citing works
Structure Elucidation of Colibactin and Its DNA Cross-Links
Xue, M., Kim, C. S., Healy, A. R., Wernke, K. M., Wang, Z., Frischling, M. C., Shine, E. E., Wang, W., Herzon, S. B., & Crawford, J. M. (2019) · Science · doi:10.1126/science.aax2685 · Cited by 257 · see citing works
Quantitative profiling of colorectal cancer-associated bacteria reveals associations between Fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer
Viljoen, K. S., Dakshinamurthy, A., Goldberg, P., & Blackburn, J. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119462 · Cited by 256 · see citing works
Interplay between the lung microbiome and lung cancer
Mao, Q., Jiang, F., Yin, R. H., Wang, J., Xia, W., Dong, G., Ma, W., Yang, Y., Xu, L., & Hu, J. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.11.036 · Cited by 251 · see citing works
The NF-κB Signaling Pathway, the Microbiota, and Gastrointestinal Tumorigenesis: Recent Advances
Peng, C., Ouyang, Y., Lü, N., & Li, N. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01387 · Cited by 257 · see citing works
Microbiome in Colorectal Cancer: How to Get from Meta-omics to Mechanism?
Ternes, D., Karta, J., Tsenkova, M., Wilmes, P., Haan, S., & Letellier, E. (2020) · Trends in Microbiology · doi:10.1016/j.tim.2020.01.001 · Cited by 256 · see citing works
Probiotics, prebiotics and colorectal cancer prevention
Ambalam, P. S., Raman, M., Purama, R. K., & Doble, M. (2016) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2016.02.009 · Cited by 251 · see citing works
Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
Cao, Y., Oh, J., Xue, M., Huh, W. J., Wang, J., González-Hernández, J. A., Rice, T., Martin, A. L., Song, D., Crawford, J. M., et al. (2022) · Science · doi:10.1126/science.abm3233 · Cited by 251 · see citing works
The colibactin warhead crosslinks DNA
Vizcaino, M. I., & Crawford, J. M. (2015) · Nature Chemistry · doi:10.1038/nchem.2221 · Cited by 247 · see citing works
Difference of lower airway microbiome in bilateral protected specimen brush between lung cancer patients with unilateral lobar masses and control subjects
Liu, H., Tao, L., Zhang, J., Zhu, Y., Zheng, Y., Liu, D., Zhou, M., Ke, H., Shi, M., & Qu, J. (2018) · International Journal of Cancer · doi:10.1002/ijc.31098 · Cited by 235 · see citing works
Dysbiosis of the Gut Microbiome in Lung Cancer
Zhuang, H., Cheng, L., Wang, Y., Zhang, Y.-K., Zhao, M.-F., Liang, G.-D., Zhang, M.-C., Li, Y.-G., Zhao, J.-B., Gao, Y.-N., et al. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00112 · Cited by 235 · see citing works
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 234 · see citing works
Colibactin: More Than a New Bacterial Toxin
Faïs, T., Delmas, J., Barnich, N., Bonnet, R., & Dalmasso, G. (2018) · Toxins · doi:10.3390/toxins10040151 · Cited by 227 · see citing works
Bacterial infections and cancer
van Elsland, D. M., & Neefjes, J. (2018) · EMBO Reports · doi:10.15252/embr.201846632 · Cited by 216 · see citing works
Cellular senescence: Molecular mechanisms and pathogenicity
Wei, W., & Ji, S. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.26956 · Cited by 205 · see citing works
The role of gut microbiota in the pathogenesis of colorectal cancer
Zhu, Q., Gao, R., Wu, W., & Qin, H. (2013) · Tumor Biology · doi:10.1007/s13277-013-0684-4 · Cited by 210 · see citing works
Cancer‐associated fecal microbial markers in colorectal cancer detection
Eklöf, V., Löfgren‐Burström, A., Zingmark, C., Edin, S., Larsson, P. G., Karling, P., Alexeyev, O. A., Rutegård, M., Wikberg, M. L., & Palmqvist, R. (2017) · International Journal of Cancer · doi:10.1002/ijc.31011 · Cited by 209 · see citing works
High fat diet, gut microbiome and gastrointestinal cancer
Tong, Y., Gao, H., Qi, Q., Liu, X., Li, J., Gao, J., Li, P., Wang, Y., Du, L., & Wang, C. (2021) · Theranostics · doi:10.7150/thno.56157 · Cited by 205 · see citing works
Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development
Allen, J., & Sears, C. L. (2019) · Genome Medicine · doi:10.1186/s13073-019-0621-2 · Cited by 205 · see citing works
Gut microbiota and colorectal cancer
Gao, R., Gao, Z., Huang, L., & Qin, H. (2017) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-016-2881-8 · Cited by 205 · see citing works
Immune System, Microbiota, and Microbial Metabolites: The Unresolved Triad in Colorectal Cancer Microenvironment
Hanus, M., Parada‐Venegas, D., Landskron, G., Wielandt, A. M., Hurtado, C., Álvarez, K., Hermoso, M. A., López-Köstner, F., & la Fuente, M. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.612826 · Cited by 201 · see citing works
Collateral damage: Insights into bacterial mechanisms that predispose host cells to cancer
Gagnaire, A., Nadel, B., Raoult, D., Neefjes, J., & Gorvel, J.-P. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.171 · Cited by 189 · see citing works
Therapeutic methods of gut microbiota modification in colorectal cancer management – fecal microbiota transplantation, prebiotics, probiotics, and synbiotics
Kaźmierczak-Siedlecka, K., Daca, A., Fic, M., van de Wetering, T., Folwarski, M., & Makarewicz, W. (2020) · Gut Microbes · doi:10.1080/19490976.2020.1764309 · Cited by 191 · see citing works
Understanding the role of the gut microbiome in gastrointestinal cancer: A review
Ağagündüz, D., Cocozza, E., Cemali, Ö., Bayazıt, A. D., Nanì, M. F., Cerqua, I., Morgillo, F., Saygılı, S. K., Berni Canani, R., Amero, P., et al. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1130562 · Cited by 189 · see citing works
A Prodrug Resistance Mechanism Is Involved in Colibactin Biosynthesis and Cytotoxicity
Brotherton, C. A., & Balskus, E. P. (2013) · Journal of the American Chemical Society · doi:10.1021/ja312154m · Cited by 186 · see citing works
Metabiotics: One Step ahead of Probiotics; an Insight into Mechanisms Involved in Anticancerous Effect in Colorectal Cancer
Sharma, M., & Shukla, G. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01940 · Cited by 187 · see citing works
Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer
Domenico, E. G. D., Cavallo, I., Pontone, M., Toma, L., & Ensoli, F. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091887 · Cited by 183 · see citing works
Host-microbial Cross-talk in Inflammatory Bowel Disease
Nagao‐Kitamoto, H., & Kamada, N. (2017) · Immune Network · doi:10.4110/in.2017.17.1.1 · Cited by 179 · see citing works
Pathogenicity Factors of Genomic Islands in Intestinal and Extraintestinal Escherichia coli
Desvaux, M., Dalmasso, G., Beyrouthy, R., Barnich, N., Delmas, J., & Bonnet, R. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.02065 · Cited by 186 · see citing works
Genomic aberrations after short-term exposure to colibactin-producing E. coli transform primary colon epithelial cells
Iftekhar, A., Berger, H., Bouznad, N., Heuberger, J., Boccellato, F., Dobrindt, U., Hermeking, H., Sigal, M. J., & Meyer, T. F. (2021) · Nature Communications · doi:10.1038/s41467-021-21162-y · Cited by 175 · see citing works
Pathogenic role of the gut microbiota in gastrointestinal diseases
Nagao‐Kitamoto, H., Kitamoto, S., Kuffa, P., & Kamada, N. (2016) · Intestinal Research · doi:10.5217/ir.2016.14.2.127 · Cited by 174 · see citing works
Colorectal cancer: the facts in the case of the microbiota
Clay, S. L., Fonseca-Pereira, D., & Garrett, W. S. (2022) · Journal of Clinical Investigation · doi:10.1172/jci155101 · Cited by 166 · see citing works
Gut Microbiota Dysbiosis Drives the Development of Colorectal Cancer
Fan, X., Jin, Y., Chen, G., Ma, X., & Zhang, L. (2020) · Digestion · doi:10.1159/000508328 · Cited by 169 · see citing works
Pharmacomicrobiomics: The Impact of Human Microbiome Variations on Systems Pharmacology and Personalized Therapeutics
ElRakaiby, M. T., Dutilh, B. E., Rizkallah, M. R., Boleij, A., Cole, J. N., & Aziz, R. K. (2014) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2014.0018 · Cited by 167 · see citing works
Colorectal cancer occurrence and treatment based on changes in intestinal flora
Si, H., Yang, Q. F., Hu, H., Ding, C., Wang, H., & Lin, X. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.05.004 · Cited by 162 · see citing works
Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression
Brennan, C. A., Clay, S. L., Lavoie, S., Bae, S., Lang, J. K., Fonseca‐Pereira, D., Rosinski, K. G., Ou, N., Glickman, J. N., & Garrett, W. S. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1987780 · Cited by 162 · see citing works
Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities
Pandey, H., Tang, D. W. T., Wong, S. H., & Lal, D. (2023) · Cancers · doi:10.3390/cancers15030866 · Cited by 165 · see citing works
Genotoxicity of Escherichia coli Nissle 1917 strain cannot be dissociated from its probiotic activity
Olier, M., Marcq, I., Salvador–Cartier, C., Sécher, T., Dobrindt, U., Boury, M., Bacquie, V., Pénary, M., Gaultier, E., Nougayrède, J., et al. (2012) · Gut Microbes · doi:10.4161/gmic.21737 · Cited by 156 · see citing works
Self-citation
Bacterial Biofilms in Colorectal Cancer Initiation and Progression
Li, S., Konstantinov, S. R., Smits, R., & Peppelenbosch, M. P. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.11.004 · Cited by 154 · see citing works
Defense contracts: molecular protection in insect-microbe symbioses
Arnam, E. B. V., Currie, C. R., & Clardy, J. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00340d · Cited by 155 · see citing works
The Gastrointestinal Tumor Microenvironment
Quante, M., Varga, J., Wang, T. C., & Greten, F. R. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.03.052 · Cited by 153 · see citing works
The Bacterium Frischella perrara Causes Scab Formation in the Gut of its Honeybee Host
Engel, P., Bartlett, K. D., & Moran, N. A. (2015) · mBio · doi:10.1128/mbio.00193-15 · Cited by 151 · see citing works
Strain-level epidemiology of microbial communities and the human microbiome
Yan, Y., Nguyen, L. H., Franzosa, E. A., & Huttenhower, C. (2020) · Genome Medicine · doi:10.1186/s13073-020-00765-y · Cited by 147 · see citing works
Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer
Boleij, A., & Tjalsma, H. (2012) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2012.00218.x · Cited by 145 · see citing works
Linking Gut Microbiota to Colorectal Cancer
Raskov, H., Burcharth, J., & Pommergaard, H. (2017) · Journal of Cancer · doi:10.7150/jca.20497 · Cited by 151 · see citing works
The gut microbiome: what the oncologist ought to know
Lee, K. A., Luong, M., Shaw, H. M., Nathan, P., Bataille, V. A., & Spector, T. D. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01467-x · Cited by 151 · see citing works
Role of Endogenous Microbiota, Probiotics and Their Biological Products in Human Health
Howarth, G. S., & Wang, H. (2013) · Nutrients · doi:10.3390/nu5010058 · Cited by 140 · see citing works
Host/microbiota interactions in health and diseases—Time for mucosal microbiology!
Daniel, N., Lécuyer, E., & Chassaing, B. (2021) · Mucosal Immunology · doi:10.1038/s41385-021-00383-w · Cited by 141 · see citing works
The Role of the Gut Microbiota in Colorectal Cancer Causation
Hinai, E. A., Walton, G., & Commane, D. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215295 · Cited by 141 · see citing works
Intestinal microbiota and its association with colon cancer and red/processed meat consumption
Abu‐Ghazaleh, N., Chua, W. J., & Gopalan, V. (2020) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15042 · Cited by 151 · see citing works

Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli
Pleguezuelos-Manzano, C., Puschhof, J., Rosendahl Huber, A., van Hoeck, A., Wood, H. M., Nomburg, J., Gurjao, C., Manders, F., Dalmasso, G., Stege, P. B., et al. (2020) · Nature · doi:10.1038/s41586-020-2080-8 · Cited by 1,208 · see citing works
In vitro genotoxicity analyses of colibactin-producing E. coli isolated from a Japanese colorectal cancer patient
Kawanishi, M., Hisatomi, Y., Oda, Y., Shimohara, C., Tsunematsu, Y., Sato, M., Hirayama, Y., Miyoshi, N., Iwashita, Y., Yoshikawa, Y., et al. (2019) · The Journal of Toxicological Sciences · doi:10.2131/jts.44.871 · Cited by 20 · see citing works
Escherichia coli strains with the capacity for long-term persistence in the bowel microbiota carry the potentially genotoxic pks island
Nowrouzian, F. L., & Oswald, É. (2012) · Microbial Pathogenesis · doi:10.1016/j.micpath.2012.05.011 · Cited by 107 · see citing works
Microbiology: A strain on the relationship
(2010) · Nature · doi:10.1038/465848c
Prevalence and association of pks+ Escherichia coli with colorectal cancer in patients at the University Malaya Medical Centre, Malaysia
Iyadorai, T., Mariappan, V., Vellasamy, K. M., Wanyiri, J. W., Roslani, A. C., Lee, G. K., Sears, C. L., & Vadivelu, J. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228217 · Cited by 116 · see citing works

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)
ORCID: Marcq, Ingrid
Nougayrède, Jean-Philippe
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
DOI: 10.1073/pnas.1001261107
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 › Biochemistry, Genetics and Molecular Biology › Endocrinology › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks