Lemercier Claudie
Inserm UMR_S 1038, biologie à grande échelle (BGE), 38054 Grenoble, France - CEA, institut de recherches en technologies et sciences pour le vivant (iRTSV), BEG, 38054 Grenoble, France - Université Grenoble-Alpes, 38000 Grenoble, France.
Med Sci (Paris). 2014 Aug-Sep;30(8-9):758-64. doi: 10.1051/medsci/20143008013. Epub 2014 Sep 1.
An increasing number of studies report that infection by pathogenic bacteria alters the host genome, producing highly hazardous DNA double strand breaks for the eukaryotic cell. Even when DNA repair occurs, it often leaves "scars" on chromosomes that might generate genomic instability at the next cell division. Chronic intestinal inflammation promotes the expansion of genotoxic bacteria in the intestinal microbiote which in turn triggers tumor formation and colon carcinomas. Bacteria act at the level of the host DNA repair machinery. They also highjack the host cell cycle to allow themselves time for replication in an appropriate reservoir. However, except in the case of bacteria carrying the CDT nuclease, the molecular mechanisms responsible for DNA lesions are not well understood, even if reactive oxygen species released during infection make good candidates.
越来越多的研究报告称,病原菌感染会改变宿主基因组,为真核细胞产生极具危害的DNA双链断裂。即使发生了DNA修复,它也常常会在染色体上留下“疤痕”,这可能会在下次细胞分裂时导致基因组不稳定。慢性肠道炎症会促进肠道微生物群中具有基因毒性的细菌扩张,进而引发肿瘤形成和结肠癌。细菌作用于宿主DNA修复机制层面。它们还会劫持宿主细胞周期,以便在合适的宿主细胞中争取到复制所需的时间。然而,除了携带细胞毒素基因座(CDT)核酸酶的细菌外,即便感染过程中释放的活性氧是造成DNA损伤的有力候选因素,但导致DNA损伤的分子机制仍未完全明确。