Department of Microbiology, Biocenter, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany.
Nat Rev Microbiol. 2015 Dec;13(12):741-8. doi: 10.1038/nrmicro3537. Epub 2015 Nov 9.
In recent years, numerous bacterial pathogens have been shown to inactivate the major tumour suppressor p53 during infection. This inactivation impedes the protective response of the host cell to the genotoxicity that often results from bacterial infection. Moreover, a new aspect of the antibacterial activity of p53 that has recently come to light - downregulation of host cell metabolism to interfere with intracellular bacterial replication - has further highlighted the crucial role of p53 in host-pathogen interactions, as host cell metabolism is relevant for all intracellular bacteria, as well as other pathogens that replicate inside host cells and use host metabolites. In this Progress article, we summarize recent work that has advanced our knowledge of the interaction between pathogenic bacteria and p53, and we discuss the known and expected outcomes of this interaction for pathogenesis.
近年来,大量的细菌病原体在感染过程中被证实能够使主要的肿瘤抑制因子 p53 失活。这种失活会阻碍宿主细胞对细菌感染通常导致的遗传毒性的保护反应。此外,最近发现 p53 的一个新的抗菌活性方面 - 下调宿主细胞代谢以干扰细胞内细菌复制 - 进一步强调了 p53 在宿主-病原体相互作用中的关键作用,因为宿主细胞代谢与所有细胞内细菌以及其他在宿主细胞内复制并利用宿主代谢物的病原体都有关。在这篇进展文章中,我们总结了最近的工作,这些工作提高了我们对致病菌与 p53 之间相互作用的认识,并讨论了这种相互作用对发病机制的已知和预期结果。