a Department of Molecular Pathology and Biology , Faculty of Military Health Sciences, University of Defence , Hradec Kralove , Czech Republic.
Virulence. 2018 Dec 31;9(1):754-770. doi: 10.1080/21505594.2018.1441588.
The nucleoid-associated HU proteins are small abundant DNA-binding proteins in bacterial cell which play an important role in the initiation of DNA replication, cell division, SOS response, control of gene expression and recombination. HU proteins bind to double stranded DNA non-specifically, but they exhibit high affinity to abnormal DNA structures as four-way junctions, gaps or nicks, which are generated during DNA damage. In many pathogens HU proteins regulate expression of genes involved in metabolism and virulence. Here, we show that the Francisella tularensis subsp. holarctica gene locus FTS_0886 codes for functional HU protein which is essential for full Francisella virulence and its resistance to oxidative stress. Further, our results demonstrate that the recombinant FtHU protein binds to double stranded DNA and protects it against free hydroxyl radicals generated via Fenton's reaction. Eventually, using an iTRAQ approach we identified proteins levels of which are affected by the deletion of hupB, among them for example Francisella pathogenicity island (FPI) proteins. The pleiotropic role of HU protein classifies it as a potential target for the development of therapeutics against tularemia.
类核相关 HU 蛋白是细菌细胞中含量丰富的小型 DNA 结合蛋白，在 DNA 复制起始、细胞分裂、SOS 反应、基因表达和重组的控制中发挥重要作用。HU 蛋白非特异性地结合双链 DNA，但它们对异常的 DNA 结构（如四链结、缺口或小裂口）具有高亲和力，这些结构是在 DNA 损伤过程中产生的。在许多病原体中，HU 蛋白调节参与代谢和毒力的基因表达。在这里，我们表明，土拉弗朗西斯菌亚种 holarctica 的 FTS_0886 基因座编码功能性 HU 蛋白，该蛋白对弗朗西斯菌的完全毒力及其对氧化应激的抗性是必需的。此外，我们的结果表明，重组 FtHU 蛋白与双链 DNA结合，并保护其免受通过 Fenton 反应产生的游离羟自由基的侵害。最终，我们使用 iTRAQ 方法鉴定了 hupB 缺失影响的蛋白水平，其中包括例如弗朗西斯氏菌致病性岛（FPI）蛋白。HU 蛋白的多效性作用将其归类为开发针对兔热病的治疗方法的潜在靶标。
