Making a quantum leap in plaque research with modern sciences

利用现代科学实现牙菌斑研究的巨大飞跃

• 批准号: 8460437
• 负责人: Renate Lux
• 金额: $ 37.36万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460437
• 关键词: 10 year old; Acids; Address; Adult; Bacteria; Behavior; Biological; Biological Process; Biology; Carbohydrates; Caries prevention; Characteristics; Chemistry; Child; Clinical Management; Collaborations; Communities; Complex; DNA; Data; Dental; Dental Enamel; Dental Plaque; Dental caries; Dentistry; Detection; Development; Dietary Carbohydrates; Dimensions; Disease; Disease Progression; Dyes; Ecology; Effectiveness; Engineering; Environment; Epidemic; Excision; Fermentation; Fluorescent Dyes; Fluorescent Probes; Fluorides; Future; Gingiva; Goals; Green Fluorescent Proteins; Health; In Situ; Incidence; Incubated; Individual; Institutes; Isotopes; Knowledge; Label; Laboratories; Laser Scanning Confocal Microscopy; Lead; Learning; Left; Link; Malnutrition; Maps; Measures; Mechanics; Mediating; Metabolic; Metabolism; Methods; Microbial Biofilms; Mission; Molecular Biology; Monitor; Monoclonal Antibodies; National Institute of Dental and Craniofacial Research; Oral; Oral Microbiology; Oral cavity; Oral health; Organism; Pacific Northwest; Pathogenesis; Peptides; Population; Prevalence; Process; Production; Property; Proteins; Public Health; RNA; Research; Research Personnel; Role; Saliva; Sampling; Schools; Science; Source; Spatial Distribution; Stimulus; Streptococcus mutans; Sucrose; System; Techniques; Technology; Testing; Therapeutic Effect; Time; Treatment Cost; Treatment Protocols; United States; Virulence; Work; antimicrobial; antimicrobial peptide; base; cariogenic bacteria; commensal microbes; improved; in vivo; insight; interest; killings; microbial; microbial community; microbicide; microorganism; new therapeutic target; novel; novel strategies; novel therapeutic intervention; oral bacteria; oral biofilm; oral pathogen; oral plaque; organic acid; pathogen; prototype; public health relevance; quantum; research study; stable isotope; success; tool

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.

描述(由申请人提供)：目前预防龋齿的方法包括用氟化物硬化釉质，以及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饮食碳水化合物产生降低pH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最初的下降在几年前就达到了平台期。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。进一步发展这些“移除并杀死所有”方法不太可能显著改善口腔健康。只有通过扩大我们对微生物介导的导致龋齿的过程的理解，才能实现革命性的进步。这将需要一张牙菌斑生物的详细图片，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，以提供对涉及龋齿形成的生物过程的详细了解。这将包括对已知病原体的致龋性及其对产酸的影响的全面分析。此外，我们还将提供目前尚不清楚产酸功能的物种的代谢活动信息。根据NIDCR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病流行的有针对性的战略。我们将结合复杂的、特定于物种的活体标记工具(单抗和表达荧光蛋白的细菌)与产酸监测(pH敏感染料、荧光蛋白和核磁共振图谱)、使用稳定同位素探测(SIP)标记酸性活性物种。这些工具将揭示牙菌斑中有关物种、物种间相互作用和有助于龋齿(产酸)或健康(体内平衡)条件的代谢过程的细节。这项应用的第二个目标将检查我们之前开发的针对致龋性变形链球菌的特定靶向抗菌肽(STAMP)的潜力，以将菌斑生态转向健康的菌斑。我们将进一步改进目前在酸性环境中激活的抗菌肽原型，并开发更多针对已知的致龋性物种以及本项目中确定的抗菌肽。这项研究将极大地扩展我们对斑块内导致疾病的生物过程的知识，并提供新的治疗方法，旨在通过专门去除致龋性物种并保持有益或无害的人群不变来实现长期的口腔健康。