Salmonella Facilitates Iron Acquisition through UMPylation of Ferric Uptake Regulator.
Salmonella Facilitates Iron Acquisition through UMPylation of Ferric Uptake Regulator.
复制标题
YdiU 通过 UMPylation 和停用铁吸收调节剂促进沙门氏菌获取铁
作者：
铁限制是细菌感染时机体免疫的普遍策略。然而，病原体拮抗宿主营养免疫的机制尚未完全阐明。在这里，我们确定了沙门氏菌中该过程对UMPylator YdiU的要求。金属饥饿信号显著诱导YdiU的表达。ΔydiU菌株的细胞内铁含量远低于野生型沙门氏菌，并且ΔydiU菌株在金属缺乏环境下表现出严重的生长缺陷。全基因组表达分析显示，与野生型菌株相比，ΔydiU菌株铁吸收基因的表达显著降低。有趣的是，YdiU在体内和体外不影响主要铁摄取调节剂Fur的表达水平，但直接在其H118残基上UMPylated Fur。UMPylation破坏了Fur二聚体，促进了Fur聚集，并消除了Fur的DNA结合活性，从而消除了Fur抑制铁吸收的能力。将毛皮限制在去UMPylated状态显著消除了缺铁环境中的沙门氏菌铁摄取。同时，YdiU通过调节铁摄取途径促进沙门氏菌在宿主细胞内的存活。
Iron limitation is a universal strategy of host immunity during bacterial infection. However, the mechanisms by which pathogens antagonize host nutritional immunity have not been fully elucidated. Here, we identified a requirement for the UMPylator YdiU for this process in Salmonella. The expression of YdiU was dramatically induced by the metal starvation signal. The intracellular iron content was much lower in the ΔydiU strain than in wild-type Salmonella, and the ΔydiU strain exhibited severe growth defect under metal deficiency environments. Genome-wide expression analyses revealed significantly decreased expression of iron uptake genes in ΔydiU strain compared with the wild-type strain. Interestingly, YdiU did not affect the expression level of the major iron uptake regulator Fur but directly UMPylated Fur on its H118 residue in vivo and in vitro. UMPylation destroyed the Fur dimer, promoted Fur aggregation, and eliminated the DNA-binding activity of Fur, thus abolishing the ability of Fur to inhibit iron uptake. Restricting Fur to the deUMPylated state dramatically eliminates Salmonella iron uptake in iron deficiency environments. In parallel, YdiU facilitates Salmonella survival within host cells by regulating the iron uptake pathway.
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DOI：
10.1073/pnas.1218274110
发表时间：
2013-07-16
影响因子：
11.1
作者：
Frawley, Elaine R.;Crouch, Marie-Laure V.;Fang, Ferric C.
通讯作者：
Fang, Ferric C.
影响因子：
3.2
作者：
Hall, HK;Foster, JW
通讯作者：
Foster, JW
影响因子：
3.2
作者：
Kehres, DG;Janakiraman, A;Maguire, ME
通讯作者：
Maguire, ME
影响因子：
8.9
作者：
NEILANDS, JB
通讯作者：
NEILANDS, JB
影响因子：
4.8
作者：
Friedman, YE;O'Brian, MR
通讯作者：
O'Brian, MR