Ler is a negative autoregulator of the LEE1 operon in enteropathogenic Escherichia coli
Ler is a negative autoregulator of the LEE1 operon in enteropathogenic Escherichia coli
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DOI：
10.1128/jb.187.1.349-357.2005
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Rosenshine, I
中科院分区：
文献类型：
--
作者：
Berdichevsky, T;Friedberg, D;Rosenshine, I
肠病性大肠杆菌 (EPEC) 会导致幼儿严重腹泻。 LEE 致病岛是宿主肠道定植所必需的，它由编码 III 型分泌系统和相关蛋白质的操纵子簇组成。 LEE1 操纵子编码 Ler，它正向调节 LEE 区域和染色体其他位置的许多 EPEC 毒力基因。我们发现 Ler 作为 LEE1 转录的特异性自阻遏物。我们进一步表明，Ler 在体内和体外特异性结合 LEE1 操纵子的上游。 Ler 与不同 DNA 区域的亲和力的比较表明，自动调节机制将 Ler 的稳态水平限制在刚好足以激活 LEE2 和 LEE3 启动子以及可能其他 LEE 启动子的浓度。这种机制可能反映了 EPEC 需要平衡通过增加毒力基因的表达来最大化定植效率和通过限制其表达来最小化宿主的免疫反应。此外，我们发现自动调节机制降低了 LEE1 表达水平的细胞间变异性。我们的研究结果指出了一种新的负调节电路，可以抑制噪音并优化 ler 和其他 LEE1 基因的表达水平。
Enteropathogenic Escherichia coli (EPEC) causes severe diarrhea in young children. Essential for colonization of the host intestine is the LEE pathogenicity island, which comprises a cluster of operons encoding a type III secretion system and related proteins. The LEE1 operon encodes Ler, which positively regulates many EPEC virulence genes in the LEE region and elsewhere in the chromosome. We found that Ler acts as a specific autorepressor of LEE1 transcription. We further show that Ler specifically binds upstream of the LEE1 operon in vivo and in vitro. A comparison of the Ler affinities to different DNA regions suggests that the autoregulation mechanism limits the steady-state level of Ler to concentrations that are just sufficient for activation of the LEE2 and LEE3 promoters and probably other LEE promoters. This mechanism may reflect the need of EPEC to balance maximizing the colonization efficiency by increasing the expression of the virulence genes and minimizing the immune response of the host by limiting their expression. In addition, we found that the autoregulation mechanism reduces the cell-to-cell variability in the levels of LEE1 expression. Our findings point to a new negative regulatory circuit that suppresses the noise and optimizes the expression levels of ler and other LEE1 genes.