Specificity of Streptococcus mutans sugar transporters

描述(申请人提供)：变形链球菌的糖运输和代谢与牙菌斑的发生和发展直接相关，导致人类龋齿(龋齿)的形成。在变形链球菌中，糖底物被ABC转运蛋白和磷酸烯醇式丙酮酸(PEP)-糖磷酸转移酶系统(PTS)摄取。为了更好地了解这种重要的牙科病原体的糖运输和代谢，我们使用表达芯片对变形链球菌UA159的整体转录进行了分析。然而，其中许多转运蛋白的特异性仍不清楚。由于碳水化合物的吸收和代谢是生龋酸形成和释放的关键步骤，了解和了解所有变形链球菌糖转运蛋白的特异性是非常重要的。因此，这项建议的具体目的是： 1)利用表型芯片(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体负责一个或多个碳水化合物的运输，而特定的碳水化合物由一个、两个(或多个)转运体运输。因此，这项研究的结果将提供变形链球菌利用的碳源的文库，并将确定其糖转运蛋白的底物。这种方法是新颖和创新的，因为虽然已经研究了变形链球菌中一些单独的糖转运蛋白的专一性，但大多数底物的专一性仍然是未知的。此外，这是一种高通量分析，可以同时筛选190种不同的糖基质。这一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球转录分析。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了解，并促进旨在减少龋齿发病率的新的治疗和预防方法。 公共卫生相关性：变形链球菌的糖代谢与牙菌斑的发生和发展直接相关，导致人类龋齿(龋齿)的形成。碳水化合物的吸收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运输是非常重要的。这项研究的结果将提供变形链球菌利用的碳源的库，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应该会极大地促进我们对这种重要的人类病原体的理解。

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.