Borrelia host adaptation Regulator (BadR) regulates rpoS to modulate host adaptation and virulence factors in Borrelia burgdorferi.
Borrelia host adaptation Regulator (BadR) regulates rpoS to modulate host adaptation and virulence factors in Borrelia burgdorferi.
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DOI：
10.1111/mmi.12171
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发表时间：
2013-04
影响因子：
3.6
通讯作者：
Seshu J
中科院分区：
文献类型：
--
作者：
Miller CL;Karna SL;Seshu J
伯氏疏螺旋体的RpoS转录因子是“看门人”，因为它激活螺旋体从蜱虫转变为脊椎动物宿主所需的基因。然而，RpoS如何被抑制以允许螺旋体从脊椎动物宿主转变回蜱虫载体仍然是未知的。在这里，我们表明，一个假定的碳水化合物响应调节蛋白，指定BadR（疏螺旋体宿主适应调节器），是一个转录阻遏rpoS。B中BadR水平升高。在模拟未进食蜱和badR缺陷型菌株的体外条件下生长的伯氏培养物在这些相同条件下生长有缺陷。badR缺陷型菌株的微阵列和免疫印迹分析显示rpoS和其他对脊椎动物宿主中的毒力重要的因子的上调，以及推定的蜱特异性决定簇（例如线性质粒28-4基因）的下调。DNA结合试验表明BadR与rpoS上游区域结合。BadR中的定点突变和磷酸化糖的存在影响BadR与rpoS启动子的结合。badR缺陷型B。burgdorferi不能在小鼠中定殖。已经确定了几个假定的蜱特异性靶点。我们的研究确定了一种新的调节剂，BadR，并提供了营养环境线索之间的联系，利用螺旋体适应蜱和脊椎动物宿主中发现的不同条件。
The RpoS transcription factor of Borrelia burgdorferi is a “gatekeeper” because it activates genes required for spirochetes to transition from tick to vertebrate hosts. However, it remains unknown how RpoS becomes repressed to allow the spirochetes to transition back from the vertebrate host to the tick vector. Here we show that a putative carbohydrate-responsive regulatory protein, designated BadR (Borrelia host adaptation Regulator), is a transcriptional repressor of rpoS. BadR levels are elevated in B. burgdorferi cultures grown under in vitro conditions mimicking unfed-ticks and badR-deficient strains are defective for growth under these same conditions. Microarray and immunoblot analyses of badR-deficient strains showed up-regulation of rpoS and other factors important for virulence in vertebrate hosts, as well as down-regulation of putative tick-specific determinants (e.g. linear plasmid 28-4 genes). DNA-binding assays revealed BadR binds to upstream regions of rpoS. Site-directed mutations in BadR and the presence of phosphorylated sugars affected BadR’s binding to the rpoS promoters. badR-deficient B. burgdorferi were unable to colonize mice. Several putative tick-specific targets have been identified. Our study identified a novel regulator, BadR, and provides a link between nutritional environmental cues utilized by spirochetes to adaptation to disparate conditions found in the tick and vertebrate hosts.