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Mechanisms for adaptation to oxidative stress in Porphyromonas gingivalis

牙龈卟啉单胞菌适应氧化应激的机制

基本信息

批准号：
8452601
负责人：
Hansel M. Fletcher
金额：
$ 46.09万
依托单位：
LOMA LINDA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-08 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8452601
关键词：
Affinity Amino Acid Sequence Anaerobic Bacteria Base Excision Repairs Binding Binding Sites Cleaved cell DNA DNA Damage DNA Repair Development Disease Environment Exposure to Fractionation Gene Expression Genes Genetic Transcription Genome Goals Health Human Hydrogen Peroxide Inflammatory Knowledge Lesion Life Modification Mutagenesis Mutation Nucleotide Excision Repair Oligonucleotides Operon Organism Oxidation-Reduction Oxidative Stress PAWR protein Pathogenicity Pathway interactions Peptide Sequence Determination Periodontal Diseases Periodontal Pocket Pigments Play Porphyromonas gingivalis Prevention Promoter Regions Property Proteins Reaction Reporting Research Resistance Role Stress Structure Testing Time Up-Regulation UvrC protein Virulence design mouse model mutant novel therapeutic intervention novel therapeutics pathogen public health relevance repaired resistance mechanism response sensor success

项目摘要

DESCRIPTION (provided by applicant): Mechanisms for adaptation to oxidative stress in Porphyromonas gingivalis Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The inflammatory environment of the periodontal pocket suggests that this organism has properties that will facilitate its ability live in an oxidative environment. There is a gap in our knowledge of mechanism(s) of oxidative stress resistance in P. gingivalis and other periodontal pathogens. It is our hypothesis that in P. gingivalis multiple coordinately regulated mechanisms are vital for protection against oxidative stress and are significant in the pathogenicity of the organism. In preliminary studies, we have used a global approach to assess the transcription profile of the cellular response of isogenic mutants of P. gingivalis in an environment of oxidative stress typical of the periodontal pocket. The response to hydrogen peroxide (H2O2)-induced oxidative stress identified the induced expression of several genes including some known to be involved in oxidative stress resistance. The duration of oxidative stress was shown to differentially modulate transcription with the up-regulation of DNA repair/modification genes mostly seen at a shorter exposure time. During a longer exposure to oxidative stress, several genes known to be involved in protein repair were up-regulated. Over the range of exposure times, there was an up-regulation of several hypothetical genes which have not been previously characterized. Our previous report has also demonstrated that, in contrast to other organisms, the repair of oxidative stress-induced DNA damage involving 8-oxo-7,8-dihydroguanine (8-oxoG) may occur by a yet-to-be described mechanism in P. gingivalis. In this project, we wish to gain a comprehensive understanding of how P. gingivalis adapts to the oxidative conditions typical of the periodontal pocket and evaluate whether it contributes to its pathogenicity. The Specific Aims are: 1. To characterize the specific role(s) of oxidative stress-induced genes in the survival/pathogenicity of P. gingivalis. 2. To identify and characterize the regulatory sequences and protein(s) involved in the expression of the grpE locus. 3. To characterize the DNA damage and mechanism(s) of repair in isogenic mutants of P. gingivalis under conditions of oxidative stress. Collectively, this information could provide important clues that would allow the development of novel therapeutic interventions to aid in the control and prevention of periodontal disease and other P. gingivalis-associated diseases.

描述（由申请人提供）：牙龈卟啉单胞菌适应氧化应激的机制牙龈卟啉单胞菌是一种黑色素革兰氏阴性厌氧菌，是牙周病的重要病因。牙周袋的炎症环境表明该生物体具有促进其在氧化环境中生存的特性。我们对牙龈卟啉单胞菌和其他牙周病原体的氧化应激抵抗机制的了解存在差距。我们的假设是，在牙龈卟啉单胞菌中，多种协调调节机制对于防止氧化应激至关重要，并且在生物体的致病性中具有重要意义。在初步研究中，我们使用全局方法来评估牙龈卟啉单胞菌等基因突变体在牙周袋典型氧化应激环境中细胞反应的转录谱。对过氧化氢 (H2O2) 诱导的氧化应激的反应确定了几种基因的诱导表达，其中包括一些已知参与氧化应激抵抗的基因。研究表明，氧化应激的持续时间可以差异性地调节转录，DNA 修复/修饰基因的上调主要在较短的暴露时间内出现。在长时间暴露于氧化应激的情况下，一些已知参与蛋白质修复的基因被上调。在暴露时间范围内，一些先前未表征的假设基因出现了上调。我们之前的报告还表明，与其他生物体相比，牙龈卟啉单胞菌中涉及 8-oxo-7,8-二氢鸟嘌呤 (8-oxoG) 的氧化应激诱导的 DNA 损伤的修复可能通过尚未描述的机制发生。在这个项目中，我们希望全面了解牙龈卟啉单胞菌如何适应牙周袋典型的氧化条件，并评估它是否有助于其致病性。具体目标是： 1. 表征氧化应激诱导基因在牙龈卟啉单胞菌存活/致病性中的具体作用。 2. 鉴定和表征参与 grpE 基因座表达的调控序列和蛋白质。 3. 表征氧化应激条件下牙龈卟啉单胞菌等基因突变体的 DNA 损伤和修复机制。总的来说，这些信息可以提供重要的线索，从而开发新的治疗干预措施，以帮助控制和预防牙周病和其他牙龈卟啉单胞菌相关疾病。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Role of the Porphyromonas gingivalis iron-binding protein PG1777 in oxidative stress resistance.

牙龈卟啉单胞菌铁结合蛋白 PG1777 在氧化应激抵抗中的作用。

DOI：
10.1099/mic.0.000213
发表时间：
2016
期刊：
Microbiology (Reading, England)
影响因子：
0
作者：
McKenzie,RachelleME;Henry,LeroyG;Boutrin,Marie-Claire;Ximinies,Alexia;Fletcher,HanselM
通讯作者：
Fletcher,HanselM

Local and Systemic Effects of Porphyromonas gingivalis Infection.