TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, 300457, China.
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin, 300071, China.
Int Microbiol. 2020 Aug;23(3):381-390. doi: 10.1007/s10123-019-00110-3. Epub 2019 Dec 13.
Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important gram-negative intracellular pathogen that infects humans and animals. More than 50 putative regulatory proteins have been identified in the S. Typhimurium genome, but few have been clearly defined. In this study, the physiological function and regulatory role of STM14_3563, which encodes a ParD family putative transcriptional regulator in S. Typhimurium, were investigated. Macrophage replication assays and mice experiments revealed that S. Typhimurium showed reduced growth in murine macrophages and attenuated virulence in mice owing to deletion of STM14_3563 gene. RNA sequencing (RNA-Seq) data showed that STM14_3563 exerts wide-ranging effects on gene expression in S. Typhimurium. STM14_3563 activates the expression of several genes encoded in Salmonella pathogenicity island (SPI)-6, SPI-12, and SPI-13, which are required for intracellular replication of S. Typhimurium. Additionally, the global transcriptional regulator Fis was found to directly activate STM14_3563 expression by binding to the STM14_3563 promoter. These results indicate that STM14_3563 is involved in the regulation of a variety of virulence-related genes in S. Typhimurium that contribute to its growth in macrophages and virulence in mice.
肠炎沙门氏菌血清型 Typhimurium（S. Typhimurium）是一种重要的革兰氏阴性细胞内病原体，可感染人类和动物。在 S. Typhimurium 基因组中已经鉴定出超过 50 种假定的调节蛋白，但很少有明确界定的。在这项研究中，研究了编码 S. Typhimurium 中 ParD 家族假定转录调节因子的 STM14_3563 的生理功能和调节作用。巨噬细胞复制实验和小鼠实验表明，由于 STM14_3563 基因的缺失，S. Typhimurium 在小鼠巨噬细胞中的生长减少，毒力减弱。RNA 测序（RNA-Seq）数据显示，STM14_3563 对 S. Typhimurium 中的基因表达具有广泛的影响。STM14_3563 激活了沙门氏菌致病岛（SPI）-6、SPI-12 和 SPI-13 中几个基因的表达，这些基因是 S. Typhimurium 细胞内复制所必需的。此外，全局转录调节因子 Fis 被发现通过结合 STM14_3563 启动子直接激活 STM14_3563 的表达。这些结果表明，STM14_3563 参与 S. Typhimurium 中多种与毒力相关基因的调节，这些基因有助于其在巨噬细胞中的生长和在小鼠中的毒力。
