Metal-oxidative stress interplay in periodontopathogen Prevotella intermedia

铁-氧相互作用在建立感染中至关重要， 病原体逃避宿主反应并在宿主内繁殖。虽然它不同 在厌氧菌中显著，包括牙周病原体如卟啉单胞菌 牙龈菌和中间普雷沃菌，与需氧菌相比， 关于厌氧细菌中的铁稳态。我们已经证明，许多假定的 在牙龈卟啉单胞菌和 然而，我们的数据还表明，中间普雷沃氏菌的直向同源物 摄取调节剂Fur不是牙龈卟啉单胞菌中主要的铁稳态调节剂， 这种细菌中一定存在铁调节的新机制。 此外，牙龈卟啉单胞菌氧化应激调节剂OxyR参与氯化血红素的合成。 体内平衡基于铁依赖性的显著差异， 调控，我们假设，差异超出属卟啉单胞菌 并且包括属于拟杆菌门的其它厌氧细菌。这里我们 建议通过描述P. intermedia的作用来扩展我们的调查 在这种细菌的铁稳态中，铁吸收调节剂Fur的直向同源物。 此外，由于铁在氧化应激物质的产生中起着至关重要的作用，我们将 还研究了氧化应激调节剂的中间型疟原虫同源物的作用， OxyR首先，我们将使用 生物测定以及基因和蛋白质表达的基因组谱分析。接下来， 我们将定义中间对虾中Fur和OxyR的调节子。如P. intermedia 厌氧细菌，并与众所周知的好氧，α 变形菌，如大肠杆菌，我们假设新的发现将获得 从这次调查中。我们的研究结果将有助于确定铁和氧化 应力稳态机制，反过来可能作为未来设计的目标， 中间青霉的抗菌剂。由于P. intermedia在遗传学上相似， 对于许多其它厌氧医学上重要的细菌， 用于制定其他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.