Specificity of Streptococcus mutans sugar transporters

变形链球菌糖转运蛋白的特异性

• 批准号: 7450643
• 负责人: DRAGANA AJDIC
• 金额: $ 7.33万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-07 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7450643
• 关键词: ATP-Binding Cassette Transporters; Acids; Carbohydrates; Carbon; Complement; Dental; Dental Plaque; Dental caries; Development; Genome; Human; Incidence; Individual; Laboratories; Libraries; Metabolism; Microbial Biofilms; Phenotype; Phosphoenolpyruvate; Phosphoenolpyruvate Sugar Phosphotransferase System; Phosphotransferases; Prevention; Public Health; Screening procedure; Source; Specificity; Streptococcus mutans; Substrate Specificity; System; carbohydrate metabolism; high throughput analysis; innovation; novel; novel strategies; pathogen; sugar; uptake

DESCRIPTION (provided by applicant): Sugar transport and metabolism by Streptococcus mutans is directly related to the onset and development dental plaque, leading to the formation of human dental caries (tooth decay). In S. mutans, sugar substrates are taken up by ABC transporters and by phosphoenolpyruvate (PEP)-sugar phosphotransferase systems (PTSs). To better understand sugar transport and metabolism of this important dental pathogen, we have performed global transcriptional analysis of S. mutans UA159 using Expression microarrays. However, the specificity of many of these transporters has remained unknown. Since the uptake and metabolism of carbohydrates is the key step in the formation and release of cariogenic acid, it is very important to know and understand the specificity of all S. mutans sugar transporters. Therefore, the specific aim of this proposal is to: 1) identify the carbohydrate specificity of S. mutans UA159 sugar transporters using phenotype microarrays (PMs). We hypothesize that the specific sugar transporter is responsible for transport of one or more carbohydrates, and that a particular carbohydrate is transported by one, two (or more) transporters. Therefore, the results of this study will provide a library of carbon sources utilized by S. mutans, and will identify substrates for its sugar transporters. This approach is novel and innovative in that while the specificity of some individual sugar transporters in S. mutans have been studied, the substrate specificity for most of them is still unknown. Also, this is a high-throughput analysis that will allow screening of 190 different sugar substrates simultaneously. This analysis will also complement global transcriptional analysis of S. mutans sugar transporters that has been successfully accomplished in our laboratory. The information obtained from the proposed study should dramatically advance our understanding of this important human pathogen and facilitate new approaches for treatment and prevention aimed at reducing the incidence of dental caries. PUBLIC HEALTH RELEVANCE: Sugar metabolism by Streptococcus mutans is directly related to the onset and development dental plaque, leading to the formation of human dental caries (tooth decay). The uptake and metabolism of carbohydrates is the key step in the formation and release of cariogenic acid, therefore is very important to understand sugar transport of S. mutans. The results of this study will provide a library of carbon sources utilized by S. mutans, and will identify substrates for its sugar transporters. The information obtained from the proposed study should dramatically advance our understanding of this important human pathogen.

描述（申请人提供）：变形链球菌的糖转运和代谢与牙菌斑的发生和发展直接相关，导致人类龋齿（蛀牙）的形成。在变形链球菌中，糖底物被 ABC 转运蛋白和磷酸烯醇丙酮酸 (PEP)-糖磷酸转移酶系统 (PTS) 吸收。为了更好地了解这种重要的牙科病原体的糖转运和代谢，我们使用表达微阵列对变形链球菌 UA159 进行了全局转录分析。然而，许多这些转运蛋白的特异性仍然未知。由于碳水化合物的摄取和代谢是致龋酸形成和释放的关键步骤，因此了解和了解所有变形链球菌糖转运蛋白的特异性非常重要。因此，本提案的具体目标是： 1) 使用表型微阵列 (PM) 鉴定变形链球菌 UA159 糖转运蛋白的碳水化合物特异性。 我们假设特定的糖转运蛋白负责运输一种或多种碳水化合物，并且特定的碳水化合物由一种、两种（或更多种）转运蛋白运输。因此，这项研究的结果将提供变形链球菌利用的碳源库，并将确定其糖转运蛋白的底物。这种方法是新颖的和创新的，因为虽然已经研究了变形链球菌中一些个体糖转运蛋白的特异性，但其中大多数糖转运蛋白的底物特异性仍然未知。此外，这是一种高通量分析，可同时筛选 190 种不同的糖底物。该分析还将补充我们实验室已成功完成的变形链球菌糖转运蛋白的全局转录分析。从拟议的研究中获得的信息将极大地促进我们对这种重要的人类病原体的理解，并促进旨在减少龋齿发生率的治疗和预防新方法。 公共健康相关性：变形链球菌的糖代谢与牙菌斑的发生和发展直接相关，从而导致人类龋齿（蛀牙）的形成。碳水化合物的摄取和代谢是致龋酸形成和释放的关键步骤，因此了解变形链球菌的糖转运非常重要。这项研究的结果将提供变形链球菌利用的碳源库，并将确定其糖转运蛋白的底物。从拟议的研究中获得的信息将极大地促进我们对这种重要的人类病原体的理解。