Molecular Biology of Oral Alkali Production

口服碱生产的分子生物学

• 批准号: 6765103
• 负责人: Robert A Burne
• 金额: $ 25.21万
• 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/6765103
• 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）：生成碱，以氨的形式；