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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。变形链球菌的糖转运和代谢与人类龋齿（蛀牙）的发生和形成直接相关。在变形链球菌中，糖底物被ABC转运体（例如麦芽糖转运和多种糖代谢转运（MSM）系统）、特定渗透物和最常见的磷酸烯醇丙酮酸(PEP)-糖磷酸转移酶系统（PTS）所吸收。为了更好地了解这种重要的牙齿病原体，我们在俄克拉荷马大学对菌株UA159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显示，存在5个ABC转运体和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。由于碳水化合物的摄取和代谢是蛀牙酸形成和释放的关键步骤，并且由于变形链球菌菌株UA159的基因组DNA序列的完成现在允许我们定位所有预测的编码区域，本建议的工作将研究变形链球菌的全局基因反应。此外，由于变形链球菌生长在斑块中，而斑块是一种天然的生物膜，因此确定生物膜培养物中基因表达的变化至关重要。因此，本提案的具体目标是：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）存在时观察到的全局基因表达差异；2)通过单独灭活这些系统，确定变形链球菌浮游培养物和生物膜中相同糖（以及受运输系统影响的基因）的多个转运体。我们假设许多基因在不同的碳水化合物来源和培养状态下会有不同的表达模式。从拟议的研究中获得的信息将极大地促进我们对这一重要人类病原体的理解，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.