Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Emerg Microbes Infect. 2021 Dec;10(1):461-471. doi: 10.1080/22221751.2021.1899054.
causes human monocytic ehrlichiosis (HME), which is one of the most prevalent, life-threatening emerging infectious zoonoses. The life cycle of includes ticks and mammals, in which proteins are expressed differentially contributing to bacterial survival and infection. Among the P28-OMP outer membrane proteins, OMP-1B and P28 are predominantly expressed in tick cells and mammalian macrophages, respectively. The mechanisms regulating this differential expression have not been comprehensively studied. Here, we demonstrate that the transcriptional regulators EcxR and Tr1 regulate the differential expression of and in Recombinant Tr1 bound to the promoters of and and transactivated and promoter-EGFP fusion constructs in . The consensus sequence of Tr1 binding motifs was A/TATA as determined with DNase I footprint assay. Tr1 showed a higher affinity towards the promoter than the promoter as determined with surface plasmon resonance. EcxR activated the expression in response to a temperature decrease. At 37°C low level of Tr1 activated the expression. At 25°C high level of Tr1 activated the expression, while repressing the expression by binding to an additional site upstream of the gene. Our data provide insights into a novel mechanism mediated by Tr1 regulating differential gene expression, which may aid in the development of new therapeutics for HME.
导致人类单核细胞埃立克体病（HME），这是最普遍的、威胁生命的新兴传染病之一。的生命周期包括蜱和哺乳动物，其中蛋白表达不同，有助于细菌的存活和感染。在 28-OMP 外膜蛋白中，OMP-1B 和 P28 分别主要在蜱细胞和哺乳动物巨噬细胞中表达。调节这种差异表达的机制尚未得到全面研究。在这里，我们证明转录调节剂 EcxR 和 Tr1 调节 和 在 中的差异表达。重组 Tr1 与 和 启动子结合，并在 中转录激活 和 启动子-EGFP 融合构建体。Tr1 结合基序的共有序列如 DNase I 足迹测定所示为 A/TATA。Tr1 与 启动子的结合亲和力高于 启动子，如表面等离子体共振测定所示。EcxR 响应温度下降激活 表达。在 37°C 时，低水平的 Tr1 激活 表达。在 25°C 时，高水平的 Tr1 激活 表达，同时通过结合 基因上游的另一个位点来抑制 表达。我们的数据提供了一种新的机制的见解，即 Tr1 调节 差异基因表达，这可能有助于开发 HME 的新疗法。
