Molecular Biology of Oral Alkali Production

口服碱生产的分子生物学

• 批准号: 6916358
• 负责人: Robert A Burne
• 金额: $ 25.2万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916358
• 关键词: Streptococcus; acid base balance; acidity /alkalinity; aminohydrolases; ammonia; arginine; bacterial genetics; carbohydrates; dental caries; disease /disorder model; enzyme activity; enzyme induction /repression; enzyme mechanism; genetic regulation; genetic regulatory element; laboratory rat; microorganism metabolism; molecular biology; molecular cloning; mutant; oral bacteria; oral health; pathologic process; transcription factor; urea; urease

DESCRIPTION (provided by applicant): Alkali generation, in the form of ammonia, is a major impediment to the initiation and progression of dental caries. There is also indirect evidence to support that ammonia production impacts calculus deposition by promoting mineral precipitation, and it may also exacerbate periodontal diseases by impairing the function of normal host immune and repair processes. There are two major sources of ammonia in the mouth: urea and arginine, which are hydrolyzed by ureases and the arginine deiminase system (ADS) of oral bacteria, respectively. During the previous funding periods, substantial insight was gained about the molecular architecture, genetic regulation, the role of ureases of oral bacteria in physiologic homeostasis and the importance of alkali generation in caries inhibition. This proposal builds on our previous studies with the ureases of oral bacteria, focusing on two fundamental areas directly related to the molecular biology, physiology and role in oral diseases of ammonia production. The first continues the studies we have developed during the previous funding periods on the molecular biology of urea catabolism by oral microorganisms and the second goal is to thoroughly characterize the arginine deiminase systems (ADS) of two oral streptococci. To accomplish our goals, we have organized the project under two specific aims: Aim 1. Continued analysis of the genetics, physiology and role in oral ecology and disease of bacterial ureases focusing primarily i) on the pH- and carbohydrate-dependent expression of the urease of Streptococcus salivarius, but also ii) on the utility of recombinant, urease-producing bacteria in inhibition of dental caries and iii) on factors that may affect the ability of oral microorganisms to carry out ureolysis in the human oral cavity. Aim 2. Molecular analysis of the arginine deiminase system of Streptococcus gordinii and Streptococcus rattus focusing i) on the cis- and trans-acting factors governing induction by arginine, and repression by glucose or oxygen, ii) analysis of the role of the ADS in inhibition of the initiation and progression of dental caries using of ADS-deficient mutants of S. gordonii and S. rattus, or recombinant, arginolytic S. mutans, and iii) physiological analysis of arginine transport and analysis of the effects of fluoride on alkali-generation via the ADS. This research will provide insights into new ways to control caries and other oral infectious diseases by manipulating the capacity or oral microorganisms to produce ammonia and to modulate the pH of oral biofilms.

描述（由申请人提供）：以氨的形式产生碱， 是龋齿发生和发展的主要障碍。那里 也是支持氨生产影响微积分的间接证据 沉积通过促进矿物沉淀，它也可能加剧 牙周病通过损害宿主正常的免疫和修复功能 流程.口腔中氨的主要来源有两种：尿素和 精氨酸，其被尿素酶和精氨酸脱亚胺酶系统水解 (ADS)口腔细菌的数量。在以往的供资期间， 获得了大量关于分子结构、遗传 调节，口腔细菌的尿素酶在生理稳态中的作用， 碱生成在龋齿抑制中的重要性。这一建议建立 关于我们以前对口腔细菌尿素酶的研究，重点是两个 与分子生物学，生理学和生物学直接相关的基础领域 在口腔疾病中的作用氨的生产。第一个继续研究， 在以前的资助期间， 第二个目标是彻底清除口腔微生物中的尿素 表征精氨酸脱亚胺酶系统（ADS）的两个口腔链球菌。到 为了实现我们的目标，我们根据两个具体目标组织了该项目： 目标1.继续分析遗传学、生理学和口腔生态学中的作用 和细菌性尿素酶的疾病，主要集中在i）pH-和 唾液链球菌尿素酶的碳水化合物依赖性表达， 而且ii）重组的产脲酶细菌在 抑制龋齿和iii）可能影响 口腔微生物在人体口腔中进行尿素分解。 目标2.链球菌精氨酸脱亚胺酶系统的分子分析 gordinii和Streptococcus rattus，i）关注顺式和反式作用 控制精氨酸诱导和葡萄糖或氧抑制的因子， ii）分析ADS在抑制起始中的作用，以及 使用S.戈登和 S. rattus，或重组体，溶血性S.变异体，和iii）生理的 精氨酸转运的分析和氟对 通过ADS产生碱。这项研究将提供新的见解 控制龋齿和其他口腔传染病的方法， 能力或口腔微生物产生氨和调节pH值 口腔生物膜