Molecular Biology of Oral Alkali Production

描述（由申请人提供）：在这一竞争性更新中，我们将努力集中在与口腔细菌产碱的分子生物学、生理学和口腔疾病作用直接相关的3个基本领域。我们继续开展我们在戈登链球菌中精氨酸催化剂的分子遗传学方面开创的工作，主要关注环境pH和生长结构域调节的复杂性。第二个重点领域建立在我们在前一个资助期内启动的关于鼠链球菌精氨酸脱亚胺酶系统（ADS）的工作的基础上，该研究导致了ADS和非ADS口腔链球菌中存在的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年在变形链球菌中新的产氨途径-胍丁胺脱亚胺酶系统（AgDS）上的发现和进展的基础上。AgDS是S.变形链球菌，但我们也发现，该系统是一个关键的生态决定因素，是传播链球菌。本实验的目的是在S. mutans的目的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节的分子基础。总的来说，这些研究将提供口腔氨产生的遗传学和生理学的新的基础知识，并将在开发利用碱生成调节口腔生物膜组成和活性的方式，促进健康的菌斑生态和抑制口腔疾病的发展的治疗策略是非常宝贵的。为了实现我们的目标，我们组织，我们的研究到以下具体目标：1.戈登链球菌精氨酸脱亚胺酶系统pH和指数期后诱导的分子基础分析。2.精氨酸脱亚胺酶调节蛋白在变形链球菌中的作用。3. AguR是S.变异胍丁胺脱亚胺酶系统。

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.