Molecular Biology of Oral Alkali Production

口服碱生产的分子生物学

• 批准号: 7146566
• 负责人: Robert A Burne
• 金额: $ 27.65万
• 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 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7146566
• 关键词: Streptococcus; acid base balance; acidity /alkalinity; ammonia; arginine; bacterial genetics; carbohydrates; enzyme activity; enzyme induction /repression; enzyme mechanism; genetic regulation; genetic regulatory element; microorganism metabolism; oral bacteria; oral health; transcription factor

DESCRIPTION (provided by applicant): In this competing renewal we focus our efforts on 3 fundamental areas directly related to the molecular biology, physiology and role in oral diseases of alkali production by oral bacteria. We continue the work we pioneered on the molecular genetics of arginine catabolism in Streptococcus gordonii, focusing primarily on the complexities of regulation by environmental pH and growth domain. The second focus area builds on work we initiated during the previous grant period on the arginine deiminase system (ADS) of Streptococcus rattus, which has lead to new discoveries of ADS-associated regulatory proteins present in both ADS and non-ADS oral streptococci. The final focus area builds on discoveries and progress made over the last 3 years on a novel ammonia-producing pathway in Streptococcus mutans--the agmatine deiminase system (AgDS). The AgDS is part of the acid-adaptive regimen of S. mutans, but we also revealed that the system is a critical ecological determinant that is disseminated in streptococci. The goal of the proposed experimentation on the AgDS of S. mutans is to understand the molecular basis for the complex regulation by factors that profoundly influence oral ecology and oral disease progression. Collectively, these studies will provide new fundamental knowledge of the genetics and physiology of oral ammonia production and will be invaluable in developing therapeutic strategies that exploit alkali generation to modulate oral biofilm composition and activity in a way that promotes healthy plaque ecology and inhibits development of oral diseases. To accomplish our goals, we have organized, our studies into the following Specific Aims: 1. Analysis of the molecular basis for pH and post-exponential phase induction of the arginine deiminase system of Streptococcus gordonii. 2. Dissection of the role of arginine deiminase regulatory proteins in mutans streptococci. 3. Structure:function relationships in AguR, the transcriptional activator of the S. mutans agmatine deiminase system.

描述(由申请人提供)：在这一竞争更新中，我们将重点放在与口腔细菌产碱的分子生物学、生理学和在口腔疾病中的作用直接相关的3个基本领域。我们继续我们在戈登链球菌精氨酸分解代谢的分子遗传学方面的开创性工作，主要集中在环境pH和生长区域调节的复杂性上。第二个重点领域建立在我们在前一个赠款期间启动的关于鼠链球菌精氨酸脱亚胺酶系统(ADS)的工作基础上，这导致了在ADS和非ADS口腔链球菌中都存在ADS相关调节蛋白的新发现。最后一个重点领域建立在过去3年在变形链球菌中一种新的产氨途径--胍丁胺脱亚胺酶系统(AGDS)上的发现和进展上。AGDS是变形链球菌酸适应方案的一部分，但我们也揭示了该系统是散布在链球菌中的关键生态决定因素。拟议中的变形链球菌AGDS实验的目标是了解深刻影响口腔生态和口腔疾病进展的因素进行复杂调控的分子基础。总的来说，这些研究将提供关于口腔产氨的遗传学和生理学的新的基础知识，并将在开发治疗策略方面具有宝贵的价值，这些策略利用碱的产生来调节口腔生物膜的组成和活性，以促进健康的菌斑生态并抑制口腔疾病的发展。为了实现我们的目标，我们组织了以下具体目标的研究：1.分析戈登链球菌精氨酸脱亚胺酶体系pH和指后阶段诱导的分子基础。2.精氨酸脱亚胺酶调节蛋白在变形链球菌中的作用。3.结构：变形链球菌苷胺脱氨酶系统转录激活子AgUR的功能关系。