Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
J Bacteriol. 2011 Nov;193(21):5950-60. doi: 10.1128/JB.05557-11. Epub 2011 Aug 26.
The H-NS protein represses the transcription of hundreds of genes in Gram-negative bacteria. Derepression is achieved by a multitude of mechanisms, many of which involve the binding of a protein to DNA at the repressed promoter in a manner that compromises the maintenance of the H-NS-DNA nucleoprotein repression complex. The principal virulence gene promoters in Shigella flexneri, the cause of bacillary dysentery, are repressed by H-NS. VirB, a protein that closely resembles members of the ParB family of plasmid-partitioning proteins, derepresses the operons that encode the main structural components and the effector proteins of the S. flexneri type III secretion system. Bioinformatic analysis suggests that VirB has been co-opted into its current role as an H-NS antagonist in S. flexneri. To test this hypothesis, the potential for VirB to act as a positive regulator of proU, an operon that is repressed by H-NS, was assessed. Although VirB has no known relationship with the osmoregulated proU operon, it could relieve H-NS-mediated repression when the parS-like VirB binding site was placed appropriately upstream of the RpoD-dependent proU promoter. These results reveal the remarkable facility with which novel regulatory circuits can evolve, at least among those promoters that are repressed by H-NS.
H-NS 蛋白在革兰氏阴性菌中抑制数百个基因的转录。通过多种机制实现去阻遏，其中许多机制涉及蛋白质与 DNA 结合，在受抑制的启动子处结合，从而破坏 H-NS-DNA 核蛋白抑制复合物的维持。志贺氏菌（引起细菌性痢疾的病原体）的主要毒力基因启动子受 H-NS 抑制。VirB 是一种与质粒分配蛋白 ParB 家族成员非常相似的蛋白质，它使编码志贺氏菌 III 型分泌系统主要结构成分和效应蛋白的操纵子去阻遏。生物信息学分析表明，VirB 已被篡夺为其在志贺氏菌中的当前 H-NS 拮抗剂角色。为了验证这一假设，评估了 VirB 作为 H-NS 抑制的 proU 操纵子的正调节剂的潜力。尽管 VirB 与渗透压调节的 proU 操纵子没有已知的关系，但当类似 parS 的 VirB 结合位点被适当地放置在依赖 RpoD 的 proU 启动子的上游时，它可以缓解 H-NS 介导的抑制。这些结果揭示了新的调控回路至少在那些受 H-NS 抑制的启动子中进化的惊人能力。
