Oxidative Stress in Oral Streptococci

口腔链球菌的氧化应激

• 批准号: 7251969
• 负责人: ROBERT E MARQUIS
• 金额: $ 36.73万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7251969
• 关键词: Acids; Aerobic; Affect; American; Bacteria; Benzimidazoles; Biology; Cations; Cells; Chelating Agents; Communicable Diseases; DNA Repair; Dental Plaque; Dental caries; Development; Ecology; Enzymes; Exposure to; Fluorides; Genes; Genetic; Glutathione; Grant; Growth; Halogens; Heme; Hydrogen Peroxide; Investigation; Iron-Binding Proteins; Knowledge; Life; Metabolism; Microbe; Microbial Biofilms; Mono-S; NADH; NADH peroxidase; NADP; Nucleic Acids; Oral; Oral cavity; Organism; Oxidative Phosphorylation; Oxidative Stress; Oxidoreductase; Oxygen; Pathogenicity; Permeability; Peroxides; Physiological; Population; Production; Proteins; Public Health; Reactive Oxygen Species; Regulation; Research; Research Personnel; Respiration; Streptococcus; Streptococcus gordonii; Streptococcus mitis; Streptococcus mutans; Streptococcus sanguis; Superoxide Dismutase; Surveys; Testing; Therapeutic Uses; Transition Elements; Translational Research; Work; Zinc; allicin; antimicrobial; base; benzimidazole; catalase; genetic regulatory protein; mutant; oral bacteria; oral infection; oral streptococci; prophylactic; repair enzyme; response; small molecule; tool

DESCRIPTION (provided by applicant): The long-term objectives of the proposed research are to gain a more complete view of oxidative stress and oxidative damage to oral streptococci and to use this information to develop effective antimicrobial for control of Dental plaque pathogenicity, primarily related to Dental caries. The Specific Aims of the project are the following. Specific Aim 1 is focused on defining in more detail adaptive responses of S. mutans to oxidative stress. The definition will include determinations of factors that induce the responses, including acidification, but particularly aerobic growth and exposure to sulfhydryl agents. Determination of the details of these responses, especially their physiologic regulation, will depend on genetic tools we already have developed, including mutants in genes for protective enzymes and for regulatory proteins. Specific Aim 2 involves basic studies of respiration of oral streptococci, especially mutans streptococci, including strains isolated directly from Dental plaque, and use of mono-organism and mixed-organism biofilms. Another part of the Aim is to define in more detail the major cell targets for oxidative damage, especially proteins, and to assess the energetics of protective mechanisms against oxidative stress, most of which require ATP, NADH and/or NADPH to function. Specific Aim 3 is focused on translational research with investigation of small molecules, such as zinc cations, benzimidazoles or other sulfhydryl-reacting agents, such as allicin, chelators, fluoride and other halogens, transition metal cations and oxidative antimicrobials. The research will be closely interdigitated with the basic studies of the first 2 Specific Aims with a view to using of basic information in developing agents or combinations of agents potent for enhancing oxidative damage to oral bacteria. The translational work will include studies with mono-organism and mixed biofilms and determinations of cell/biofilm permeabilities to, and retentiveness of, the test antimicrobials to help us evaluate their potentials for prophylactic and therapeutic use in the mouth. The research is directly related to public health, primarily the control of Dental caries, which is the most prevalent infectious disease among young people in the American population and a growing problem for older Americans. The work involves basic and applied studies Aimed at a better understanding of the biology of Dental plaque bacteria related especially to oxygen metabolism and damage caused by reactive oxygen species.

描述（由申请人提供）：拟议的研究的长期目标是对口腔链球菌的氧化应激和氧化损害进行更完整的了解，并使用此信息来开发有效的抗菌剂，以控制牙齿斑块的致病性，主要与牙齿龋齿有关。该项目的具体目的是以下内容。特定目标1的重点是更详细地定义链球菌对氧化应激的自适应反应。该定义将包括确定诱导反应的因素，包括酸化，尤其是有氧生长和暴露于磺胺剂。确定这些反应的细节，尤其是它们的生理调节，将取决于我们已经开发的遗传工具，包括用于保护酶和调节蛋白的基因中的突变体。具体目的2涉及口服链球菌的呼吸，尤其是Mutans链球菌的呼吸，包括直接从牙菌斑中分离出来的菌株，以及使用单生物和混合生物生物膜的使用。目的的另一部分是更详细地定义氧化损伤（尤其是蛋白质）的主要细胞靶标，并评估防止氧化应激的保护机制的能量学，其中大多数需要ATP，NADH和/或NADPH才能发挥作用。特定的目标3专注于转化研究，研究小分子，例如锌阳离子，苯甲酰唑或其他硫酰基反应剂，例如大蒜素，螯合剂，氟化物和其他卤素，过渡金属阳离子和氧化抗菌素。这项研究将与前2个特定目的的基本研究紧密相互互动，以期在开发剂或效果的组合中使用基本信息，以增强对口腔细菌的氧化损害。翻译工作将包括对单生物和混合生物膜的研究，以及对测试抗菌剂的细胞/生物膜渗透性和保留性的测定，以帮助我们评估其在口腔中预防性和治疗性使用的潜力。这项研究与公共卫生直接相关，主要是对龋齿的控制，这是美国人口中年轻人中最普遍的传染病，对于老年人来说是日益严重的问题。这项工作涉及基础研究和应用研究，旨在更好地了解与氧代谢和由活性氧引起的损害相关的牙齿菌株的生物学。