Probiotics that moderate pH and antagonize pathogens to promote oral health

益生菌可调节 pH 值并对抗病原体，促进口腔健康

基本信息

批准号：
9234521
负责人：
Robert A Burne
金额：
$ 61.5万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9234521
关键词：
Address Amino Acids Animal Model Animals Antibiotics Arginine Arginine deiminase Bacteria Behavior Biochemical Biological Biological Markers Biological Models Clinical Clinical Research Communicable Diseases Coupled Dental Dental Plaque Dental caries Development Diagnosis Disease Enzymes Formulation Foundations Future Gene Expression Profile Genetic Genetic Markers Genomics Goals Growth Health Heterogeneity Human Human Microbiome Hydrogen Peroxide In Vitro Individual Light Metabolic Metabolic Pathway Metabolism Metagenomics Methodology Microbial Biofilms Modeling Molecular Monitor Mouth Diseases Mycoses Oral cavity Oral health Organism Outcome Oxidases Peptide Hydrolases Periodontal Diseases Periodontitis Phenotype Probiotics Property Research Risk Assessment Rodent Model Role Running Science Solid Source Streptococcus Streptococcus mutans Structure Symbiosis System Testing Tissues Work bacteriocin base biomarker identification commensal microbes comparative genomics design efficacy evaluation functional genomics in vivo killings microbial microbiota microorganism mouse model novel novel marker novel therapeutics oral bacteria oral biofilm oral infection oral microbiome oral pathogen pH Homeostasis pathogen prebiotics prevent probiotic therapy public health relevance sound tool weapons

项目摘要

DESCRIPTION (provided by applicant): Numerous in vitro and in vivo studies have shown there are bacteria that may promote oral health. Many of these bacteria have the ability to use the amino acid arginine to raise dental plaque pH, thus inhibiting the formation of cavities. Additionally, many of these potentially beneficial bacteria are able to interfere with the growth o oral pathogens, like Streptococcus mutans, and to block the ability of S. mutans to produce antibiotics that kill beneficial organisms. Thus, identifying isolates of these bacteria with poten beneficial properties and understanding how they modulate disease development would be tremendously valuable in controlling oral infectious diseases, like dental caries and periodontitis The work proposed here is built on the foundation that individual isolates display a profound spectrum of anti-cariogenic properties: in their capacity to utilize arginine via the arginine deiminase system; in their capacity to exert strong antagonistic effects on the growth of oral pathogens; and in their abilities to interfere with the deployment of antagonistic molecules by oral pathogens. When implemented, the study will yield a much-needed, thorough understanding of the genomic structure and associated phenotypic behaviors of a group of abundant commensal streptococci, along with the mechanisms by which these organisms exert probiotic effects in in vitro, in an animal model, and in the human oral cavity. To accomplish these goals, Aim 1 conducts a comparative and functional genomic analysis of a discrete group of low-passage, clinical isolates to characterize the mechanisms for their enhanced capacity to moderate pH through arginine metabolism, to dissect the diverse repertoire of strategies they employ to antagonize oral pathogens, to understand the genetic basis for the ability of these isolates to resist antagonistic molecules deployed by oral pathogens, and to identify genetic markers associated with isolates that have particularly beneficial properties. In Aim 2, we will establish a mouse model of dental caries that is suitable for evaluating the capacity of, and the mechanisms by which, selected isolates from Aim 1 are able to inhibit establishment, persistence, and the initiation and progression of dental caries by S. mutans. Aim 3 will contrast gene expression patterns in isolated human dental plaque from caries-active and caries-free subjects to understand how arginine metabolic pathways and the weapons of commensals and pathogens are deployed in health and disease, as well as to identify novel genetic biomarkers for health and disease. Collectively, the study will provide a comprehensive understanding of mechanisms of pro- and pre-biotic for control of dental caries and guide the development of effective probiotics and symbiotic, while providing the added benefit of enhancing the quality of oral health risk assessments.

描述（由适用提供）：许多体外和体内研究表明，有细菌可能促进口腔健康。这些细菌中的许多都具有使用氨基酸精氨酸升高牙菌斑pH的能力，从而抑制了腔的形成。此外，许多潜在的有益细菌中的许多能够干扰诸如链球菌突变的生长O口服病原体，并阻止链球菌产生杀死有益组织的抗生素的能力。这就是说，通过有益的特性鉴定这些细菌的分离物，并了解它们如何调节疾病的发展将在控制口腔传染病中具有极高的价值，例如牙齿龋齿和牙周炎，这里提出的工作建立在基础上，即单个隔离构建，即在基础上孤立地表现出深远的抗钙化特性：在其能力上通过静脉酶依次通过artinininine deimine nimininine congininen;他们对口腔病原体生长的强烈拮抗作用的能力；并在干扰口服病原体部署拮抗分子的能力方面。实施后，该研究将产生一组丰富的共生链球菌的基因组结构和相关的表型行为，以及这些生物体在体外，动物模型和人类口腔中造成益生菌作用的机制。实现这些目标，目标1对一个离散的低通量，临床分离物进行了比较和功能性基因组分析，以表征其通过精氨酸代谢增强的机制，以增强其对现代pH的能力的增强，以通过抗抑制这些隔离的病原体的能力来解剖策略的策略，以剖析策略与具有特别有益特性的分离株相关的遗传标记。在AIM 2中，我们将建立一种龋齿的小鼠模型，该模型适用于评估AIM 1中选定的分离物的能力和机制，能够抑制S. Mutans的建立，持久性，持久性以及牙齿龋齿的主动性和进展。 AIM 3将对龋齿活性和无龋齿受试者的孤立人牙齿斑块中的基因表达模式进行对比，以了解精氨酸代谢途径如何在健康和疾病中部署在健康和疾病中，以及确定健康和疾病的新型遗传生物标志物。总的来说，这项研究将对培养牙科携带的培养基和益生元的机制提供全面的理解，并指导有效的益生菌和共生的发展，同时为提高口腔健康风险评估质量的额外好处提供了额外的好处。