Functional analysis of Bucella reveals transcriptional regulation of MarR
Functional analysis of Bucella reveals transcriptional regulation of MarR
复制标题
Bucella 的功能分析揭示了 MarR 的转录调控
DOI：
10.1016/j.micpath.2020.104201
复制
发表时间：
2020-07-01
影响因子：
3.8
通讯作者：
Zhang, Hui
中科院分区：
文献类型：
--
作者：
Deng, Xingmei;Li, Min;Zhang, Hui
布鲁氏菌病是由布鲁氏菌感染引起的人畜共患传染病。MarR家族转录因子与许多病原体适应环境变化所必需的多种生理功能密切相关。然而，MarR家族的转录因子是否参与致病性，介导的炎症反应和调节细胞内病原体布鲁氏菌的毒力基因的表达仍然是未知的。因此，我们创建了B的2308 Δ MarR 6突变体。流产2308（S2308）。使用鼠巨噬细胞系（RAW 264.7）进行毒力和炎性细胞因子测定。我们还对MarR 6进行了染色质免疫沉淀，然后进行了下一代测序（ChIP-seq）。结果表明，2308 Delta MarR 6在RAW 264.7中的存活能力显著降低。在巨噬细胞被2308 Δ MarR 6感染后，肿瘤坏死因子-α的水平（TNF-α）、白细胞介素-1 β IL-1 β、IL-6、IL-12、干扰素-γ（IFN-γ）和巨噬细胞趋化蛋白-1（MCP-1）降低，并且显著低于S2308感染组，表明2308 Δ MarR 6突变体可以减少炎性细胞因子的分泌。此外，我们检测到122个分布在布鲁氏菌基因组中的MarR 6结合的基因间ChIP-seq峰。综上所述，这项研究记录了关于MarR 6的宝贵数据。本研究结果对阐明MarR 6的功能具有重要意义。
Brucellosis is a zoonotic infectious disease caused by Brucella infection. MarR-family transcription factors are closely related to diverse physiological functions necessary for many pathogens adaptation to environmental changes. However, whether the MarR-family transcription factors are involved in virulence, mediated inflammatory responses and regulated virulence gene expression in the intracellular pathogen Brucella are still unknown. Therefore, we created a 2308 Delta MarR6 mutant of B. abortus 2308 (S2308). Virulence and inflammatory cytokines assays were performed using a murine macrophage cell line (RAW 264.7). We also performed chromatin immunoprecipitation of MarR6 followed by next-generation sequencing (ChIP-seq). The results showed that 2308 Delta MarR6 was significantly reduced survival capability in RAW 264.7. After the macrophages were infected with 2308 Delta MarR6, the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-12 (IL-12), interferon-gamma (IFN-gamma) and macrophage chemoattractant protein-1 (MCP-1) were decreased and were significantly lower than that for the S2308-infected group, indicating that the 2308 Delta MarR6 mutant could reduce the secretion of inflammatory cytokines. Furthermore, we detected 122 in-tergenic ChIP-seq peaks of MarR6 binding distributed across the Brucella genome. Taken together, the research has recorded valuable data about MarR6. Our findings are of great significance in elucidating the function of MarR6.