Metal-oxidative stress interplay in periodontopathogen Prevotella intermedia

铁-氧的相互作用在感染的建立中是必不可少的，包括 以逃避宿主的反应并在其宿主内繁殖。尽管它有所不同 尤其是厌氧菌，包括牙周病原体，如卟啉单胞菌 牙龈杆菌和中间普雷沃特氏菌与需氧菌相比鲜为人知 关于厌氧菌中铁的动态平衡。我们已经证明了许多假定的 牙龈卟啉单胞菌和牙龈卟啉单胞菌的铁摄取机制 然而，我们的数据也表明，铁的直系同源 摄取调节因子Fur不是牙龈假单胞菌中主要的铁稳态调节因子 推测这种细菌中一定存在铁调节的新机制。 此外，牙龈假单胞菌的氧化应激调节因子OxyR也与氯化血红素有关。 这种细菌的动态平衡。基于铁依赖的如此显著的差异 我们假设这种差异超出了卟啉单胞菌属的范围。 并包括属于类杆菌门的其他厌氧细菌。在这里我们 建议通过确定中间假单胞菌的作用来扩大我们的调查范围 铁摄取调节剂，毛皮，在这种细菌的铁稳态中的同源基因。 此外，由于铁在氧化应激物种的产生中起着关键作用，我们将 还研究了中间P.氧化应激调节剂的同系物的作用， OxyR.首先，我们将定义这两个调节子在中间疫霉中的生物学作用。 生物分析以及基因和蛋白质表达的基因组图谱。下一首, 我们将定义中间拟青霉中Fur和OxyR的调节因子。就像P.intermedia是 厌氧细菌，与众所周知的需氧菌阿尔法有较远的亲缘关系 变形杆菌，如大肠杆菌，我们假设会有新的发现 从这次调查中脱身。我们的研究结果将有助于定义铁和氧化 强调动态平衡机制，这反过来可能成为未来设计的目标 中间假单胞菌的抗菌剂。由于中间疫霉在系统发育上是相似的 对于许多其他厌氧医学上有重要意义的细菌来说，这样的信息也将是 应用于制定其他疾病的预防措施的替代方法 细菌。

Iron-oxygen interplay is essential in establishment of an infection that includes the ability of the pathogen to escape host response and multiply within its host. Although it differs significantly in anaerobes, that include periodontopathogens such as Porphyromonas gingivalis and Prevotella intermedia, when compared to aerobes little is known as regards the iron homeostasis in anaerobic bacteria. We have shown that many putative iron acquisition mechanisms are regulated by iron in both Porphyromonas gingivalis and Prevotella intermedia, however, our data also show that the orthologue of the ferric uptake regulator, Fur, is not the major iron homeostasis regulator in P. gingivalis pointing out that novel mechanism of iron regulation must be present in this bacterium. Furthermore, the P. gingivalis oxidative stress regulator, OxyR, is involved in hemin homeostasis in this bacterium. Based on such striking differences in iron-dependent regulation we hypothesize that the differences extend beyond the genus Porphyromonas and include other anaerobic bacteria belonging to the phylum Bacteroidetes. Here we propose to extend our investigations by characterizing the role of the P. intermedia orthologue of a ferric uptake regulator, Fur, in iron homeostasis in this bacterium. Furthermore, as iron plays crucial role in generation of oxidative stress species we will also examine the role of a P. intermedia homologue of the oxidative stress regulator, OxyR. First, we will define the biological role of the two regulators in P. intermedia using biological assays as well as genomic profiling of both gene and protein expression. Next, we will define the regulons of both Fur and OxyR in P. intermedia. As P. intermedia is anaerobic bacterium and is distantly related to the well known aerobic, alpha proteobacteria such as Escherichia coli, we hypothesize novel findings will be gained from this investigation. The results of our study will help to define iron and oxidative stress homeostasis mechanisms that in turn may serve as targets for the future design of antibacterial agents for P. intermedia. Since P. intermedia is phylogenetically similar to many other anaerobic medically significant bacteria such information will also be applied in development of an alternative methods of preventive measures for other bacteria.