Molecular Biology of Oral Alkali Production

描述（由申请人提供）：在这一竞争性更新中，我们将重点放在与口腔细菌产碱的分子生物学、生理学和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上的先驱工作，主要关注环境pH和生长域调控的复杂性。第二个重点领域建立在我们在上一个资助期间开始的关于鼠链球菌精氨酸脱亚胺酶系统（ADS）的工作基础上，该工作导致ADS相关的调节蛋白在ADS和非ADS口服链球菌中都有新的发现。最后一个重点领域建立在过去3年在变形链球菌中发现和取得的新氨生成途径- AgDS系统（AgDS）的基础上。AgDS是变形链球菌酸适应方案的一部分，但我们也发现该系统是链球菌传播的关键生态决定因素。本次拟对变形链球菌的AgDS进行实验的目的是了解影响口腔生态和口腔疾病进展的复杂调节因素的分子基础。总的来说，这些研究将为口腔氨生成的遗传学和生理学提供新的基础知识，并将在开发利用碱生成来调节口腔生物膜组成和活性的治疗策略方面具有宝贵的价值，从而促进健康的菌斑生态和抑制口腔疾病的发展。为了实现我们的目标，我们将我们的学习组织成以下几个具体目标：戈多氏链球菌精氨酸脱亚胺酶系统pH和指数后相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解剖。3. 结构：在AguR中的功能关系，变异葡萄球菌agmatine脱亚胺酶系统的转录激活剂。

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.