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Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer

Abstract : Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway that leads to microsatellite instability (MSI). The present study, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased in vitro in MMR-deficient cells. Moreover, we demonstrated that colibactin-producing E. coli induce inhibition of the mutL homologue 1 (MLH1) MMR proteins, which could lead to genomic instability. However, colibactin-producing E. coli were more frequently identified in microsatellite stable (MSS) CRC. The present study suggests differences in the involvement of colibactin-producing E. coli in colorectal carcinogenesis according to the CRC phenotype. Further host-pathogen interactions studies should take into account CRC phenotypes.
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https://hal.archives-ouvertes.fr/hal-01594568
Contributor : Archive Ouverte Prodinra <>
Submitted on : Tuesday, September 26, 2017 - 8:55:06 PM
Last modification on : Wednesday, June 10, 2020 - 1:12:07 PM

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Johan Gagniere, Virginie Bonnin, Anne-Sophie Jarrousse, Emilie Cardamone, Allison Agus, et al.. Interactions between microsatellite instability and human gut colonization by Escherichia coli in colorectal cancer. Clinical Science, Portland Press, 2017, 131 (6), pp.471 - 485. ⟨10.1042/CS20160876⟩. ⟨hal-01594568⟩

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