Making a quantum leap in plaque research with modern sciences

描述（由申请人提供）：目前预防蛀牙（龋齿）的方法包括用氟化物硬化牙釉质和通过机械和一般抗菌方法去除细菌。这些方法是基于口腔菌斑细菌发酵膳食碳水化合物以产生降低ph值的有机酸的知识。在广泛实施这些措施后观察到的龋齿发病率的初步下降在几十年前达到了一个平台。今天，在美国，超过40%的10岁以下儿童以及超过85%的成年人仍然患有这种疾病，每年的治疗费用高达800亿美元。这些“清除并杀死所有”的方法的进一步发展不太可能显著改善口腔健康。革命性的进步只能通过扩大我们对导致蛀牙的微生物介导过程的理解来实现。这将需要牙菌斑有机体的详细图像，它们的代谢活动和相互作用。这项应用的长期目标是结合和应用（已建立的）先进技术，以提供对龋齿发生中涉及的生物过程的详细了解。这将包括对已知病原体的致龋潜力及其对产酸的影响的全面分析。此外，我们将提供代谢活性的信息，其功能在酸生产目前是未知的物种。根据国家疾病预防和控制中心的使命，我们将根据目前的知识和利用该项目的先进技术开发的新信息，进一步制定针对当前龋齿流行病的有针对性的战略。我们将结合复杂的，物种特异性的体内标记工具（单克隆抗体和荧光蛋白表达细菌）与酸生产监测（ph敏感染料，荧光蛋白和核磁共振谱），用稳定同位素探测（SIP）标记酸活性物种。这些工具将揭示牙菌斑中有关物种、物种间相互作用和导致龋齿（产酸）或健康（体内平衡）条件的代谢过程的细节。该应用程序的第二个目标将检查我们先前开发的针对龋齿变形链球菌的特异性靶向抗菌肽（STAMPs）的潜力，以将斑块生态转向健康斑块。我们将进一步改进目前在酸性环境中活化的原型抗菌肽，并开发更多针对已知致龋物种以及本项目中确定的物种的抗菌肽。这项研究将极大地扩展我们对导致疾病的斑块内生物过程的认识，并提供新的治疗方法，旨在通过特异性地去除致龋物种和保留有益或无害种群的完整性来实现长期口腔健康。

DESCRIPTION (provided by applicant): Current tooth decay (dental caries) prevention methods include enamel hardening with fluoride and bacterial removal via mechanical and general antimicrobial approaches. These methods are based on the knowledge that oral plaque bacteria ferment dietary carbohydrates to produce pH-reducing organic acids. Initial reductions in caries incidence observed upon widespread implementation of these measures reached a plateaudecades ago. Today more that 40% of children under 10 years of age as well as more than 85% of the adult population in the United States still suffer from the disease that cause annual treatment cost of $ 80 billion. Further development of these "remove and kill all" approaches are not likely to significantly improve oral health. Revolutionary advancements can only be achieved by expanding our understanding of the microorganism- mediated processes leading to tooth decay. This will require a detailed picture of dental plaque organisms, their metabolic activities and interactions. The long-term objective of this application is to combine and apply (established) advanced technologies to provide a detailed understanding of the biological processes involved in cariogenesis. This will include a comprehensive analysis of the cariogenic potential of known pathogens and their influence on acid production. Furthermore, we will provide information on the metabolic activity of species whose function in acid production is currently unknown. In compliance with the mission of the NIDCR we will further develop targeted strategies against the current caries epidemic based on current knowledge and the new information developed with the advanced technologies in this project. We will combine sophisticated, species-specific in vivo labeling tools (monoclonal antibodies and fluorescent protein-expressing bacteria) with monitoring of acid production (pH-sensitive dyes, fluorescent proteins and NMR profiling), labeling of acid active species with stable isotope probing (SIP). These tools will reveal details of the processes in dental plaques regarding species, interspecies interactions and the metabolic processes contributing to cariogenic (acid-producing) or healthy (homeostatic) conditions. The second goal of this application will examine the potential of our previously developed specifically targeted antimicrobial peptides (STAMPs) against cariogenic Streptococcus mutans to shift plaque ecology towards a healthy plaque. We will further improve a current prototype antimicrobial peptide that is activated in acidic environments and develop more antimicrobial peptides against known cariogenic species as well as those identified in this project. This study will greatly expand our knowledge of the biological processes within plaques that lead to disease and provide novel therapeutic approaches that aim to achieve long-term oral health by specifically removing cariogenic species and leaving beneficial or harmless populations intact.