Metal-oxidative stress interplay in periodontopathogen Prevotella intermedia

牙周病原体中间普雷沃氏菌中金属-氧化应激的相互作用

• 批准号: 9194618
• 负责人: Janina P Lewis
• 金额: $ 18.91万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9194618
• 关键词: Aerobic; Aerobic Bacteria; Alphaproteobacteria; Anaerobic Bacteria; Anti-Bacterial Agents; Bacteria; Bacteroidetes; Binding; Biochemical; Biological; Biological Assay; ChIP-seq; Data; Development; Employee Strikes; Environment; Escherichia coli; Future; Gene Expression; Gene Targeting; Generations; Hemin; Homeostasis; Homologous Gene; Immune response; Infection; Investigation; Iron; Lead; Metals; Methods; Oral; Oxidative Stress; Oxygen; Periodontal Diseases; Play; Porphyromonas; Porphyromonas gingivalis; Preventive measure; Prevotella intermedia; Proteomics; Regulation; Regulon; Role; Sampling; Therapeutic Agents; Virulence Factors; Work; base; design; environmental change; genetic regulatory protein; genomic profiles; in vivo; microbiome; novel; pathogen; periodontopathogen; protein expression; transcriptome sequencing; uptake

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.

铁氧相互作用是建立感染的必要条件，包括能力