铁是微生物必需的营养元素。其在细菌胞内的动态平衡受到全局性转录因子Fur的严格 控制。一般认为Fur通过感受胞内的铁离子浓度调控多个铁代谢相关基因以及毒力基因的表达。但这个简单的模型与许多实验现象相矛盾。最近我们发现大肠杆菌Fur并不需要直接感受铁浓度。缺铁可以诱导鞭毛抑制蛋白YdiV表达上调。当细胞内YdiV高表达时Fur转变成一种全新的状态。这种状态的Fur尽管仍然结合铁离子，却失去了结合DNA的能力。这导致铁代谢基因转录水平大幅度上调。而当细胞不缺铁时，YdiV下调，Fur随即恢复抑制相关基因表达的能力。初步数据表明这一过程是脯氨酸顺反异构酶SlyD依赖的。本项目计划运用多种微生物学技术阐明YdiV与SlyD协同调控Fur功能的分子机制，确定Fur两种状态之间具有的差异。并研究该信号通路在高致病性大肠杆菌感染宿主细胞过程中发挥的作用。

Iron is an essential nutrient for microorganisms. Iron homeostasis in bacteria is strictly controlled by the global transcription factor Fur. In general, it is believed that Fur regulates the expression of multiple iron metabolism genes and virulence genes by sensing the concentration of iron inside cells. But this simple model conflicts with many important experiments. Recently, we found that the Fur of E. coli need not sensing iron concentration directly. Iron deficiency can induce the up-regulation of flagellin inhibitor YdiV expression. When YdiV is highly expressed in cells, Fur turns into a new state. In this state, although Fur still binds iron, it completely loses its ability to bind DNA. This results in a significant up-regulation of iron metabolism genes transcription. When there is enough iron inside bacterial cells YdiV is down-regulated and Fur restores its inhibition activity to suppress corresponding genes expression. Preliminary data indicate this process is dependent on proline cis-isomerase SlyD. In this project we first plan to elucidate the molecular mechanism of how SlyD and YdiV synergistically regulate Fur function by using multiple microbial technologies. We then try to make clear what the difference between Fur in the two different states is. And we will further study how this new signaling pathway plays roles in infection of host cells by the high pathogenitic E. coli.