COBRE: UOK HSC: P 4: STREPTOCOCCUS MUTANS SUGAR TRANSPORT & BIOFILM FORMATION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。变形链球菌的糖运输和代谢与人类龋齿(龋齿)的发生和形成有直接关系。在变形链球菌中，糖底物被ABC转运蛋白(例如麦芽糖转运蛋白和多糖代谢转运蛋白(MSM)系统)、特定的渗透膜以及最常见的磷酸烯醇式丙酮酸(PEP)-糖磷酸转移酶系统(PTS)所摄取。为了更好地了解这种重要的牙科病原体，我们在俄克拉荷马大学对UA159菌株基因组的整个DNA序列进行了测序。对变形链球菌基因组的详细计算分析表明，存在5个ABC转运蛋白和14个PTS系统，可能用于糖或糖醇的运输，包括葡萄糖、蔗糖、麦芽糖、乳糖和果糖。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，而且变形链球菌UA159基因组DNA序列的完成使我们能够定位所有预测的编码区，这项拟议的工作将研究变形链球菌的整体基因反应。此外，由于变形链球菌生长在天然生物膜的菌斑中，因此确定生物膜培养中基因表达的变化是至关重要的。因此，这项建议的具体目的是1)分析变形链球菌UA159在浮游培养物和生物膜中最常见的膳食糖(蔗糖、麦芽糖、乳糖、葡萄糖和果糖)存在时观察到的全球基因表达的差异，以及2)通过单独灭活变形链球菌和生物膜培养物中相同糖的多个转运体(以及受运输系统影响的基因)。我们假设许多基因将具有不同的表达模式，以响应碳水化合物来源和培养状态的可获得性。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治疗和干预的新方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sugar transport and metabolism by Streptococcus mutans is directly related to the onset and formation of human dental caries (tooth decay). In S. mutans, sugar substrates are taken up by ABC transporters (e.g., the maltose transport and multiple sugar metabolism transport (MSM) systems), by specific permeases, and most commonly by phosphoenolpyruvate (PEP)-sugar phosphotransferase systems (PTS). To better understand this important dental pathogen, we have sequenced the entire DNA sequence of the genome of strain UA159 at the University of Oklahoma. Detailed computational analyses of the S. mutans genome showed the presence of five ABC transporters and fourteen PTS systems for the probable transport of sugars or sugar alcohols including glucose, sucrose, maltose, lactose and fructose. Since the uptake and metabolism of carbohydrates is the key step in the formation and release of cariogenic acid, and since completion of the genomic DNA sequence of S. mutans strain UA159 now permits us to locate all of the predicted coding regions, this proposed work will examine the global gene response in S. mutans. Additionally, because S. mutans grows in a plaque that is a natural biofilm, it is crucial to determine the alterations in gene expression in biofilm cultures. Therefore, the specific aims of this proposal are to 1) analyze the differences in global gene expression observed when S. mutans UA159 is grown in the presence of the most common dietary sugars (sucrose, maltose, lactose, glucose, and fructose) in planktonic culture and in biofilm, and 2) identify multiple transporters for the same sugar (as well as genes influenced by transport systems) in S. mutans planktonic and biofilm cultures by individually inactivating those systems. We hypothesize that many genes will have differential patterns of expression in response to the availability of carbohydrate source and culture state. The information obtained from the proposed study should dramatically advance our understanding of this important human pathogen and facilitate new approaches for treatment and intervention aimed at reducing the incidence of dental caries.