Potential Regulatory Role in Mammalian Host Adaptation for a Small Intergenic Region of Lp17 in the Lyme Disease Spirochete.
Potential Regulatory Role in Mammalian Host Adaptation for a Small Intergenic Region of Lp17 in the Lyme Disease Spirochete.
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DOI：
10.3389/fcimb.2022.892220
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
莱姆病的细菌病原体伯氏疏螺旋体依赖于复杂的基因调控网络在不同的硬蜱载体和哺乳动物宿主环境之间转运。我们最近报道了一个B。缺乏LP 17的转录活性基因间区域的Burgdorferi突变体由于多种抗原的表达改变而显示出减弱的鼠组织定殖和发病机制。在这项研究中，一个更详细的表征推定的调控因子编码的基因间区域进行了追求。在顺式互补菌株的突变，旨在消除潜在的蛋白质翻译能够充分的组织定植，这表明由基因间区域编码的功能性产品是不是一个蛋白质，如先前预测的。与野生型相比，基因间区域的反式互补导致该序列的转录升高，并且发现在免疫活性小鼠和免疫缺陷小鼠中完全消除感染性。野生型B基因间区转录的定量分析。Burgdorferi表明，相对于体外培养，在鼠感染期间其被高度诱导。最后，有针对性地删除该基因间区域导致转录组的显著变化，包括在传播和宿主适应中具有潜在作用的基因。本文报道的研究结果强烈表明，这部分的lp17提供了一个潜在的关键作用，在调节基因所需的适应和持久性的病原体在哺乳动物宿主。
The bacterial agent of Lyme disease, Borrelia burgdorferi, relies on an intricate gene regulatory network to transit between the disparate Ixodes tick vector and mammalian host environments. We recently reported that a B. burgdorferi mutant lacking a transcriptionally active intergenic region of lp17 displayed attenuated murine tissue colonization and pathogenesis due to altered expression of multiple antigens. In this study, a more detailed characterization of the putative regulatory factor encoded by the intergenic region was pursued. In cis complemented strains featuring mutations aimed at eliminating potential protein translation were capable of full tissue colonization, suggesting that the functional product encoded by the intergenic region is not a protein as previously predicted. In trans complementation of the intergenic region resulted in elevated transcription of the sequence compared to wild type and was found to completely abolish infectivity in both immunocompetent "and immunodeficient mice. Quantitative analysis of transcription of the intergenic region by wild-type B. burgdorferi showed it to be highly induced during murine infection relative to in vitro culture. Lastly, targeted deletion of this intergenic region resulted in significant changes to the transcriptome, including genes with potential roles in transmission and host adaptation. The findings reported herein strongly suggest that this segment of lp17 serves a potentially critical role in the regulation of genes required for adaptation and persistence of the pathogen in a mammalian host.
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影响因子：
11.3
作者：
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通讯作者：
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