Gagnière Johan, Bonnin Virginie, Jarrousse Anne-Sophie, Cardamone Emilie, Agus Allison, Uhrhammer Nancy, Sauvanet Pierre, Déchelotte Pierre, Barnich Nicolas, Bonnet Richard, Pezet Denis, Bonnet Mathilde
UMR 1071 Inserm/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.
INRA USC-2018, 63000 Clermont-Ferrand, France.
Clin Sci (Lond). 2017 Mar 1;131(6):471-485. doi: 10.1042/CS20160876. Epub 2017 Jan 16.
Recent studies suggest that colonization of colonic mucosa by pathogenic 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 colonization in the MSI CRC phenotype. In the same way, persistence and internalization were increased in MMR-deficient cells. Moreover, we demonstrated that colibactin-producing induce inhibition of the mutL homologue 1 (MLH1) MMR proteins, which could lead to genomic instability. However, colibactin-producing were more frequently identified in microsatellite stable (MSS) CRC. The present study suggests differences in the involvement of colibactin-producing in colorectal carcinogenesis according to the CRC phenotype. Further host-pathogen interactions studies should take into account CRC phenotypes.
近期研究表明，致病性细菌在结肠黏膜的定植可能与结直肠癌（CRC）的发生发展有关，特别是通过产生如大肠杆菌素等基因毒素和/或干扰导致微卫星不稳定（MSI）的DNA错配修复（MMR）途径。本研究对88例CRC患者进行，结果显示MSI CRC表型中细菌定植显著增加。同样，在MMR缺陷细胞中，细菌的持续性和内化作用增强。此外，我们证明产大肠杆菌素的细菌会诱导mutL同源物1（MLH1）MMR蛋白的抑制，这可能导致基因组不稳定。然而，产大肠杆菌素的细菌在微卫星稳定（MSS）CRC中更常见。本研究表明，根据CRC表型，产大肠杆菌素的细菌在结直肠癌发生过程中的作用存在差异。进一步的宿主-病原体相互作用研究应考虑CRC表型。
