Fur是细菌铁代谢的核心调控因子，能结合在铁吸收基因启动区使之处于关闭状态。沙门菌进入宿主细胞后，迅速逆转Fur的抑制作用，启动铁吸收抵御宿主铁胁迫的机制尚不明确。课题组前期发现沙门菌YdiU蛋白与铁吸收调控密切相关。铁胁迫可诱导沙门菌YdiU表达且敲除ydiU的菌株在缺铁条件下生存能力降低。同时，YdiU可催化Fur发生单磷酸尿苷酸化（UMP化）修饰。我们推测YdiU通过UMP化修饰Fur解除其对铁吸收基因的抑制，快速启动细菌铁吸收以抵御宿主铁胁迫。本项目拟在确定Fur的关键修饰位点基础上解析UMP-Fur的晶体结构，推导YdiU通过UMP化修饰调控Fur转录调节活性的机制模型；并通过突变菌株的细胞和动物感染模型，探讨YdiU介导的Fur的UMP化在沙门菌抵御宿主铁胁迫中的作用。本课题将为Fur的调控机制和YdiU功能研究做出重要补充，并有助于更好的理解沙门菌的胞内生存和致病机制。

Fur is the core regulator of iron metabolism in bacteria, which can bind to the promoter region of iron uptake genes and inhibit transcription of these genes. When infects cells, the mechanism of how Salmonella reverse the inhibitory effect of Fur and quickly initiate iron absorption to resist iron stress in the host was not clear. Our group found that YdiU of salmonella was closely related to the regulation of iron absorption. Under the condition of iron starvation, salmonella rapidly initiated the expression of YdiU protein. while the survival ability of salmonella strain knocking out ydiU decreased significantly under the iron- starvation stress. More importantly, YdiU can catalyze the UMPylation modification of Fur protein. We speculate that YdiU removes its inhibition of iron uptake related genes through UMP modification of Fur, and quickly initiates bacterial iron uptake to help Salmonella resist host iron stress. On the basis of determining the UMP modification site of Fur, this research will analyzes the crystal structure of UMP-Fur and deduces the molecular mechanism model of YdiU-mediated UMPylation to regulate the transcriptional regulatory activity of Fur. Through the cell and animal infection models of mutant strains, the role of UMPylation of Fur which mediated by YdiU of Salmonella in the resistance to host iron stress was discussed. This research will make an important supplement to the study of the regulatory mechanism of Fur and the function of YdiU, and contribute to a better understanding of the intracellular survival and pathogenic mechanism of Salmonella.