Molecular Biology of Oral Alkali Production

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 通过促进矿物沉淀而沉积，它还可能加剧 牙周病损害正常宿主的免疫和修复功能 流程。口腔中氨的主要来源有两种：尿素和 精氨酸，被尿素酶和精氨酸脱亚胺酶系统水解 (ADS)分别为口腔细菌。在前几个供资期间， 对分子体系结构、基因 口腔细菌尿素酶在生理动态平衡中的调节作用 碱的产生在防龋术中的重要性。这项建议建立了 在我们之前对口腔细菌尿素酶的研究基础上，重点放在两个方面 与分子生物学、生理学和生物科学直接相关的基本领域 在口腔疾病中的氨生产作用。第一个是继续我们的研究 在之前的资助期间已经在分子生物学方面取得了进展 尿素分解代谢的口腔微生物和第二个目标是彻底 描述两种口腔链球菌的精氨酸脱亚胺酶系统。至 为了实现我们的目标，我们在两个具体目标下组织了该项目： 目的1.继续分析遗传学、生理学及其在口腔生态学中的作用 和细菌性尿素酶病，主要集中在1)pH-和 唾液链球菌尿素酶的碳水化合物依赖性表达 而且ii)关于重组产生尿素酶的细菌在 抑制龋齿和III)对可能影响防腐能力的因素 口腔微生物在人体口腔内进行尿素溶解。 目的2.链球菌精氨酸脱亚胺酶系统的分子分析 戈尔迪尼和鼠链球菌聚焦于顺式和反式作用 精氨酸诱导和葡萄糖或氧气抑制的因素， 二)分析广告在抑制启动和 Gordonii和S.gordonii Ads缺陷突变株在龋病研究中的应用进展 鼠伤寒沙门氏菌，或重组的精氨酸降解变形链球菌，以及iii)生理学 精氨酸转运分析及氟对人体的影响 通过广告产生的碱。这项研究将为新的 控制龋齿和其他口腔传染病的方法 产氨能力或口腔微生物产氨和调节pH值的能力 口腔生物膜。

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.