Mlc regulation of Salmonella pathogenicity island I gene expression via hilE repression.
Mlc regulation of Salmonella pathogenicity island I gene expression via hilE repression.
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MLC通过HILE抑制调节沙门氏菌致病性岛I基因表达。
DOI：
10.1093/nar/gkm060
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发表时间：
2007
影响因子：
14.9
通讯作者：
Ryu, Sangryeol
中科院分区：
文献类型：
--
作者：
Lim, Sangyong;Yun, Jiae;Yoon, Hyunjin;Park, Chehwee;Kim, Boowon;Jeon, Byeonghwa;Kim, Dongho;Ryu, Sangryeol
全球调节剂Mlc是参与糖摄取和代谢的几个基因和操纵子的抑制因子。一株肠沙门氏菌血清型鼠伤寒杆菌mlc突变株的侵袭性和细胞毒性水平均较野生型降低，且沙门氏菌致病性岛1 （SPI1）的调控基因hilD、hilA和invF的表达水平降低。然而，在hilE突变体中未见Mlc对hilD表达和细菌侵袭性的影响，而在Mlc突变体中hilE表达增加，这表明Mlc通过降低hilE的表达对SPI1基因的表达产生积极影响，而hilE通过与hilD直接相互作用下调SPI1基因的表达。我们发现hilE的两个已知启动子不被Mlc调节，并且我们确定了第三个启动子，命名为P3，它被Mlc抑制。凝胶迁移试验和足迹分析表明，Mlc通过结合hilE P3启动子区域的两个不同位点直接抑制hilE。在Mlc调节诱导糖（如葡萄糖和甘露糖）的存在下观察到的hilD特异性下调在Mlc突变体中未被检测到。基于这些结果，我们提出Mlc的功能是感知糖的可用性，并通过其控制沙门氏菌中hilE表达的能力与毒力基因调控有关。
The global regulator Mlc is a repressor of several genes and operons that are involved in sugar uptake and metabolism. A Salmonella enterica serovar Typhimurium mlc mutant showed reduced levels of invasion and cytotoxicity compared to the wild-type, and exhibited reduced expression levels of hilD, hilA and invF, which are regulatory genes in the Salmonella pathogenicity island 1 (SPI1). However, the effects of Mlc on hilD expression and bacterial invasiveness were not seen in the hilE mutant, and hilE expression was increased in the mlc mutant, which suggests that Mlc exerts positive effects on the expression of SPI1 genes by reducing the expression of HilE, which is known to down-regulate the expression of SPI1 genes through direct interaction with HilD. We found that the two known promoters of hilE were not modulated by Mlc, and we identified a third promoter, designated P3, which was repressed by Mlc. The gel mobility shift assay and footprinting analysis revealed that Mlc repressed hilE in a direct manner by binding to two distinct sites in the hilE P3 promoter region. The specific down-regulation of hilD observed in the presence of Mlc regulon-inducible sugars, such as glucose and mannose, could not be detected in the mlc mutant. Based on these results, we propose that Mlc functions to sense the availability of sugars and is linked to virulence gene regulation by its ability to control hilE expression in Salmonella.