Siegl Christine, Prusty Bhupesh K, Karunakaran Karthika, Wischhusen Jörg, Rudel Thomas
Department of Microbiology, University of Würzburg Biocenter, Am Hubland, 97074 Würzburg, Germany.
Frauenklinik, University Clinic Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany.
Cell Rep. 2014 Nov 6;9(3):918-29. doi: 10.1016/j.celrep.2014.10.004. Epub 2014 Oct 30.
Obligate intracellular bacteria depend entirely on nutrients from the host cell for their reproduction. Here, we show that obligate intracellular Chlamydia downregulate the central tumor suppressor p53 in human cells. This reduction of p53 levels is mediated by the PI3K-Akt signaling pathway, activation of HDM2, and subsequent proteasomal degradation of p53. The stabilization of p53 in human cells severely impaired chlamydial development and caused the loss of infectious particle formation. DNA-damage-induced p53 interfered with chlamydial development through downregulation of the pentose phosphate pathway (PPP). Increased expression of the PPP key enzyme glucose-6-phosphate dehydrogenase rescued the inhibition of chlamydial growth induced by DNA damage or stabilized p53. Thus, downregulation of p53 is a key event in the chlamydial life cycle that reprograms the host cell to create a metabolic environment supportive of chlamydial growth.
专性胞内细菌完全依赖宿主细胞提供的营养进行繁殖。在此，我们表明专性胞内的衣原体可下调人类细胞中的核心肿瘤抑制因子p53。p53水平的降低是由PI3K-Akt信号通路、HDM2的激活以及随后p53的蛋白酶体降解介导的。人类细胞中p53的稳定严重损害了衣原体的发育，并导致感染性颗粒形成的丧失。DNA损伤诱导的p53通过下调磷酸戊糖途径（PPP）干扰衣原体的发育。PPP关键酶葡萄糖-6-磷酸脱氢酶表达的增加挽救了由DNA损伤或稳定的p53诱导的衣原体生长抑制。因此，p53的下调是衣原体生命周期中的一个关键事件，它对宿主细胞进行重编程以创造一个支持衣原体生长的代谢环境。
