Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, United States.
Front Cell Infect Microbiol. 2022 May 2;12:892220. doi: 10.3389/fcimb.2022.892220. eCollection 2022.
The bacterial agent of Lyme disease, , relies on an intricate gene regulatory network to transit between the disparate tick vector and mammalian host environments. We recently reported that a 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. 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. 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 showed it to be highly induced during murine infection relative to 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.
伯氏疏螺旋体，莱姆病的细菌病原体，依赖于一个复杂的基因调控网络，在不同的蜱媒介和哺乳动物宿主环境之间转换。我们最近报道，一个缺乏 lp17 中一个转录活跃的基因间区的突变体由于多个抗原表达的改变而表现出减弱的鼠组织定殖和发病机制。在这项研究中，对基因间区编码的假定调节因子进行了更详细的表征。具有旨在消除潜在蛋白质翻译的突变的 互补菌株能够完全进行组织定殖，这表明基因间区编码的功能产物不是以前预测的蛋白质。与野生型相比，基因间区的互补导致序列转录水平升高，并发现它完全消除了免疫功能正常和免疫缺陷小鼠的感染性。通过野生型 的基因间区转录的定量分析表明，与 培养物相比，它在鼠感染期间高度诱导。最后，该基因间区的靶向缺失导致转录组发生显著变化，包括可能在传播和宿主适应中起作用的基因。本研究报告的结果强烈表明，lp17 的这一片段在调节适应和病原体在哺乳动物宿主中持续存在所需的基因方面可能发挥着至关重要的作用。
