Specificity of Streptococcus mutans sugar transporters

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。In S.在变形杆菌中，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）摄取。为了更好地了解这种重要的牙齿病原体的糖转运和代谢，我们进行了S。变形杆菌UA 159的表达。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，因此了解和理解所有S.变异糖转运蛋白。因此，本提案的具体目标是： 1)鉴定S.使用表型微阵列（PM）分析变异株UA 159糖转运蛋白。 我们假设特定的糖转运蛋白负责一种或多种碳水化合物的转运，并且特定的碳水化合物由一种，两种（或更多）转运蛋白转运。因此，本研究的结果将提供一个碳源库利用的S。变异，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，而在S。尽管已经研究了变形杆菌，但是它们中的大多数的底物特异性仍然是未知的。此外，这是一种高通量分析，可以同时筛选190种不同的糖底物。该分析也将补充S.变异糖转运蛋白，已成功地在我们的实验室完成。从拟议的研究中获得的信息应该大大提高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病率的治疗和预防的新方法。 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（蛀牙）的形成。糖类物质的摄取和代谢是致龋酸形成和释放的关键步骤，因此了解S.变异人本研究的结果将提供一个碳源库的利用S。变异，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大大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.