Regulation of Streptococcus mutans PTS Transporters

变形链球菌 PTS 转运蛋白的调节

基本信息

批准号：
8868095
负责人：
DRAGANA AJDIC
金额：
$ 38.25万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-11 至 2018-06-30
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：变形链球菌的糖转运和代谢与通常称为牙菌斑的生物膜的发生和发展直接相关，从而导致人类龋齿（蛀牙）的形成。在变形链球菌中，糖底物被 ABC 转运蛋白吸收，更常见的是被磷酸烯醇丙酮酸 (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。对变形链球菌的详细转录分析表明存在 5 个组成型转录蛋白和 11 个诱导型糖转运蛋白。我们还定义了大多数这些转运蛋白的糖特异性。本申请提出通过关注 PTS 糖转运蛋白来获得有关变形链球菌碳水化合物转运调节的知识。我们假设 PTS 糖转运蛋白之间存在调节层级；具体来说，几个 PTS 参与其他 PTS 的调节，并且这种调节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，它们在浮游培养物和生物膜中控制诱导型 PTS 的调节；（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。由于碳水化合物的摄取和代谢是致龋酸形成和释放的关键步骤，因此完成所提出的实验将为理解并可能干扰变形链球菌的致龋性提供高度相关的信息。