Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles Microorganisms Year : 2024

Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis

Denis Mestivier
Iradj Sobhani

Abstract

Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive Escherichia coli (pks+ E. coli) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways.
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Dates and versions

hal-04595171 , version 1 (30-05-2024)

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Mohammad Sadeghi, Denis Mestivier, Iradj Sobhani. Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis. Microorganisms, 2024, 12 (6), pp.1111. ⟨10.3390/microorganisms12061111⟩. ⟨hal-04595171⟩

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