Regulation of Streptococcus mutans PTS Transporters

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菌斑的生物膜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转运蛋白摄取，更常见的是被磷酸烯醇丙酮酸（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，我们对S. mutans UA 159的表达。对S.变形杆菌显示存在五种组成型转录和十一种诱导型糖转运蛋白。我们还确定了大多数这些转运蛋白的糖特异性。本申请旨在获得关于S.通过专注于PTS糖转运蛋白。我们假设PTS糖转运蛋白之间存在一个调节层次，具体而言，几个PTS参与了其他PTS的调节，并且这种调节是碳水化合物特异性的。因此，我们提出：（目的1）识别S.变异株UA 159，其控制在增殖培养物和生物膜中诱导型PTS的调节;和（目的2和3）表征增殖培养物和生物膜中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，因此完成拟议的实验将为理解和可能干扰S.变异人 公共卫生相关性：葡萄球菌的碳水化合物摄取和代谢。变形杆菌与牙菌斑的发生和发展直接相关，导致人类龋齿的形成。生物体能够表达和协调调节多种吸收系统以响应可用的碳水化合物。然而，缺乏这些吸收系统的调节以及它们如何优先利用糖的细节。明确这些调控途径不仅可以促进对S.变形链球菌生理学和突出新的调控机制，但也可能导致新的方法来操纵碳水化合物的运输和代谢，以改变S。变形杆菌的持久性和毒力。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 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. PUBLIC HEALTH RELEVANCE: Carbohydrate uptake and metabolism of S. mutans is directly related to the onset and development of dental plaque, leading to the formation of human dental caries. The organism is capable of expressing and coordinately regulating multiple uptake systems in response to the available carbohydrates. However, details of the regulation of these uptake systems and how they function to prioritize sugar utilization are lacking. Defining these regulatory pathways will not only advance the understanding of S. mutans physiology and highlight novel regulatory mechanisms but also potentially lead to novel ways to manipulate carbohydrate transport and metabolism to alter S. mutans persistence and virulence. The information obtained from the proposed study should dramatically advance our understanding of this important human pathogen.