Regulation of Streptococcus mutans PTS Transporters

描述(申请人提供)：变形链球菌的糖运输和代谢与通常称为菌斑的生物膜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转运蛋白吸收，更常见的是由磷酸烯醇式丙酮酸(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运输和代谢，我们使用表达微阵列对变形链球菌UA159的整体转录进行了分析。对变形链球菌的详细转录分析表明，存在5个成分转录的糖转运蛋白和11个诱导性糖转运蛋白。我们还定义了大多数这些转运蛋白的糖专一性。这项申请建议通过专注于PTS糖转运蛋白来获得关于变形链球菌中碳水化合物运输调节的知识。我们假设在PTS糖转运体之间存在一个调控层次；具体地说，几个PTS参与了对其他PTS的调控，并且这种调控是碳水化合物特异性的。因此，我们建议：(目标1)鉴定变形链球菌UA159的PTS，它控制浮游培养物和生物膜中可诱导的PTS的调节；以及(目标2和3)表征浮游培养物和生物膜中PTS调节的分子机制。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，拟议中的实验的完成将为理解甚至干扰变形链球菌的致龋性提供高度相关的信息。

DESCRIPTION (provided by applicant): Sugar transport and metabolism by Streptococcus mutans is directly related to the onset and development of the biofilm commonly called plaque, leading to the formation of human dental caries (tooth decay). In S. mutans, sugar substrates are taken up by ABC transporters and, more commonly, by phosphoenolpyruvate (PEP)-sugar phosphotransferase systems (PTSs). To better understand sugar transport and metabolism of this important dental pathogen, we have performed global transcriptional analyses of S. mutans UA159 using expression microarrays. Detailed transcriptional analyses of S. mutans showed the presence of five constitutively transcribed and eleven inducible sugar transporters. We have also defined the sugar-specificity for most of these transporters. This application proposes to obtain knowledge regarding the regulation of carbohydrate transport in S. mutans by focusing on PTS sugar transporters. We hypothesize that there is a regulation hierarchy among PTS sugar transporters; specifically that several PTSs are involved in the regulation of the other PTSs and that this regulation is carbohydrate-specific. Accordingly, we propose to: (Aim 1) Identify PTSs of S. mutans UA159 that control regulation of inducible PTSs, in planktonic cultures and in biofilms; and (Aim 2 and 3) Characterize the molecular mechanisms of PTS regulation in planktonic cultures and in biofilms. Since the uptake and metabolism of carbohydrates are the key steps in the formation and release of cariogenic acid, the completion of the proposed experiments will provide highly relevant information for understanding, and perhaps interfering with, the cariogenicity of S. mutans.