Fur Negatively Regulates hns and Is Required for the Expression of HilA and Virulence in Salmonella enterica Serovar Typhimurium
Fur Negatively Regulates hns and Is Required for the Expression of HilA and Virulence in Salmonella enterica Serovar Typhimurium
复制标题
DOI：
10.1128/jb.00942-10
复制
发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Hassan, Hosni M.
中科院分区：
文献类型：
--
作者：
Troxell, Bryan;Sikes, Michael L.;Hassan, Hosni M.
铁是活细胞生存的必需元素。然而，过量的铁是有毒的，其吸收是由铁吸收调节剂，毛皮精细调节。在沙门氏菌中，沙门氏菌致病岛1（SPI-1）编码三型分泌系统，其是入侵小肠中的宿主上皮细胞所必需的。SPI-1的主要激活剂是编码在SPI-1中的HilA。一种已知的hilA调节剂是Fur。Fur调节hilA的机制尚不清楚。我们在这里报告说，毛皮是所需的肠道沙门氏菌血清型鼠伤寒沙门氏菌的毒力和毛皮的激活所需的hilA，以及其他HilA依赖基因，invF和sipC。HilA的Fur依赖性调节不依赖于已知的HilA阻遏物PhoP。相反，编码组蛋白样蛋白hns的基因的表达在毛皮突变体中被显著地去抑制。事实上，通过Fur激活hilA依赖于位于hns上游的28个核苷酸。此外，我们使用染色质免疫沉淀显示，在体内，毛的结合，在金属依赖的方式的hns的上游区域。最后，在一个hns突变体中的毛皮缺失导致毛皮非依赖性激活hilA。总之，Fur通过抑制hns的表达来激活hilA。
Iron is an essential element for the survival of living cells. However, excess iron is toxic, and its uptake is exquisitely regulated by the ferric uptake regulator, Fur. In Salmonella, the Salmonella pathogenicity island 1 (SPI-1) encodes a type three secretion system, which is required for invasion of host epithelial cells in the small intestine. A major activator of SPI-1 is HilA, which is encoded within SPI-1. One known regulator of hilA is Fur. The mechanism of hilA regulation by Fur is unknown. We report here that Fur is required for virulence in Salmonella enterica serovar Typhimurium and that Fur is required for the activation of hilA, as well as of other HilA-dependent genes, invF and sipC. The Fur-dependent regulation of hilA was independent of PhoP, a known repressor of hilA. Instead, the expression of the gene coding for the histone-like protein, hns, was significantly derepressed in the fur mutant. Indeed, the activation of hilA by Fur was dependent on 28 nucleotides located upstream of hns. Moreover, we used chromatin immunoprecipitation to show that Fur bound, in vivo, to the upstream region of hns in a metal-dependent fashion. Finally, deletion of fur in an hns mutant resulted in Fur-independent activation of hilA. In conclusion, Fur activates hilA by repressing the expression of hns.