一种新型 Bvg 抑制启动子导致类似于 的转录，但在 Bvg 模式下不会导致 3 型菌毛的产生。
A Novel Bvg-Repressed Promoter Causes -Like Transcription of but Does Not Result in the Production of Serotype 3 Fimbriae in Bvg Mode Bordetella pertussis.
机构信息
Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, Maryland, USA
Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, Maryland, USA.
出版信息
J Bacteriol. 2018 Sep 24;200(20). doi: 10.1128/JB.00175-18. Print 2018 Oct 15.
In , two serologically distinct fimbriae, FIM2 and FIM3, undergo on/off phase variation independently of each other via variation in the lengths of C stretches in the promoters for their major subunit genes, and These two promoters are also part of the BvgAS virulence regulon and therefore, if in an on configuration, are activated by phosporylated BvgA (BvgA~P) under normal growth conditions (Bvg mode) but not in the Bvg mode, inducible by growth in medium containing MgSO or other compounds, termed modulators. In the Tohama I strain (FIM2 FIM3), the promoter is in the off state. However, a high level of transcription of the gene is observed in the Bvg mode. In this study, we provide an explanation for this anomalous behavior by defining a Bvg-repressed promoter (BRP), located approximately 400 bp upstream of the P transcriptional start. Although transcription of the gene in the Bvg mode resulted in Fim3 translation, as measured by LacZ translational fusions, no accumulation of Fim3 protein was detectable. We propose that Fim3 protein resulting from translation of mRNA driven by BRP in the Bvg mode is unstable due to a lack of the fimbrial assembly apparatus encoded by the genes, located within the operon, and therefore is not expressed in the Bvg mode. In , the promoter P-15C for the major fimbrial subunit gene is activated by the two-component system BvgAS in the Bvg mode but not in the Bvg mode. However, many transcriptional profiling studies have shown that is transcribed in the Bvg mode even when P is in a nonpermissive state (P-13C), suggesting the presence of a reciprocally regulated element upstream of P Here, we provide evidence that BRP is the cause of this anomalous behavior of Although BRP effects -like transcription of in the Bvg mode, it does not lead to stable production of FIM3 fimbriae, because expression of the chaperone and usher proteins FimB and FimC occurs only in the Bvg mode.
在 中，两种血清学上不同的菌毛 FIM2 和 FIM3 独立地经历开/关相位变化，这是通过它们主要亚基基因启动子中 C 延伸长度的变化来实现的。这两个启动子也是 BvgAS 毒力调节子的一部分，因此，如果处于开状态，在正常生长条件下（Bvg 模式）被磷酸化的 BvgA（BvgA~P）激活，但在 Bvg 模式下不会被激活，Bvg 模式可通过在含有 MgSO 或其他化合物的培养基中生长诱导，这些化合物称为调节剂。在 Tohama I 株（FIM2 FIM3）中，启动子处于关闭状态。然而，在 Bvg 模式下观察到 基因的高水平转录。在这项研究中，我们通过定义位于 P 转录起始点上游约 400 bp 的 Bvg 抑制启动子（BRP），为这种异常行为提供了一个解释。尽管在 Bvg 模式下，基因的转录导致了 Fim3 翻译，如 LacZ 翻译融合所测量的，但无法检测到 Fim3 蛋白的积累。我们提出，由于缺乏位于 操纵子内的菌毛组装装置，由 BRP 驱动的 mRNA 翻译产生的 Fim3 蛋白不稳定，因此在 Bvg 模式下不表达。在 中，主要菌毛亚基基因 的启动子 P-15C 由 BvgAS 双组分系统在 Bvg 模式下激活，但在 Bvg 模式下不激活。然而，许多转录谱研究表明，即使 P 处于非允许状态（P-13C），也会在 Bvg 模式下转录 ，这表明 P 上游存在一个相互调节的元件。在这里，我们提供的证据表明 BRP 是 异常行为的原因。尽管 BRP 效应类似于在 Bvg 模式下转录 ，但它不会导致 FIM3 菌毛的稳定产生，因为只有在 Bvg 模式下，伴侣蛋白和 usher 蛋白 FimB 和 FimC 的表达才会发生。
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