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:
- 金额:$ 61.5万
- 依托单位:
- 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:
- 关键词:AddressAmino AcidsAnimal ModelAnimalsAntibioticsArginineArginine deiminaseBacteriaBehaviorBiochemicalBiologicalBiological MarkersBiological ModelsClinicalClinical ResearchCommunicable DiseasesCoupledDentalDental PlaqueDental cariesDevelopmentDiagnosisDiseaseEnzymesFormulationFoundationsFutureGene Expression ProfileGeneticGenetic MarkersGenomicsGoalsGrowthHealthHeterogeneityHumanHuman MicrobiomeHydrogen PeroxideIn VitroIndividualLightMetabolicMetabolic PathwayMetabolismMetagenomicsMethodologyMicrobial BiofilmsModelingMolecularMonitorMouth DiseasesMycosesOral cavityOral healthOrganismOutcomeOxidasesPeptide HydrolasesPeriodontal DiseasesPeriodontitisPhenotypeProbioticsPropertyResearchRisk AssessmentRodent ModelRoleRunningScienceSolidSourceStreptococcusStreptococcus mutansStructureSymbiosisSystemTestingTissuesWorkbacteriocinbasebiomarker identificationcommensal microbescomparative genomicsdesignefficacy evaluationfunctional genomicsin vivokillingsmicrobialmicrobiotamicroorganismmouse modelnovelnovel markernovel therapeuticsoral bacteriaoral biofilmoral infectionoral microbiomeoral pathogenpH Homeostasispathogenprebioticspreventprobiotic therapypublic health relevancesoundtoolweapons
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(由申请人提供):大量体外和体内研究表明存在可以促进口腔健康的细菌。许多这些细菌能够利用氨基酸精氨酸来提高牙菌斑的 pH 值,从而抑制蛀牙的形成。此外,许多这些潜在的有益细菌能够干扰口腔病原体(如变形链球菌)的生长,并阻止变形链球菌产生杀死有益生物的抗生素的能力。因此,鉴定具有潜在有益特性的这些细菌的分离株并了解它们如何调节疾病的发展对于控制龋齿和牙周炎等口腔传染病具有巨大的价值。这里提出的工作是建立在单个分离株表现出广泛的抗龋齿特性的基础上的:它们通过精氨酸脱亚氨酶系统利用精氨酸的能力;它们能够对口腔病原体的生长产生强烈的拮抗作用;以及它们干扰口腔病原体拮抗分子部署的能力。一旦实施,该研究将对一组丰富的共生链球菌的基因组结构和相关表型行为,以及这些生物体在体外、动物模型和人类口腔中发挥益生菌作用的机制产生急需的、彻底的了解。为了实现这些目标,目标 1 对一组离散的低传代临床分离株进行比较和功能基因组分析,以表征它们通过精氨酸代谢增强调节 pH 能力的机制,剖析它们用来拮抗口腔病原体的多种策略,了解这些分离株抵抗口腔病原体部署的拮抗分子的能力的遗传基础,以及 鉴定与具有特别有益特性的分离株相关的遗传标记。在目标 2 中,我们将建立一个龋齿小鼠模型,该模型适合评估目标 1 中选定的分离株能够抑制变形链球菌引起的龋齿形成、持续以及龋齿发生和进展的能力和机制。目标 3 将对比来自龋齿活跃和无龋齿受试者的分离的人类牙菌斑中的基因表达模式,以了解精氨酸代谢途径以及共生体和病原体的武器如何在健康和疾病中部署,以及识别健康和疾病的新型遗传生物标志物。总的来说,该研究将全面了解益生元和益生元控制龋齿的机制,指导有效益生菌和共生菌的开发,同时提供提高口腔健康风险评估质量的额外好处。
项目成果
期刊论文数量(0)
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Robert A Burne其他文献
Robert A Burne的其他文献
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{{ truncateString('Robert A Burne', 18)}}的其他基金
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
- 批准号:
10175495 - 财政年份:2020
- 资助金额:
$ 61.5万 - 项目类别:
Environmental regulation of gene expression dissected by microfluidics
微流体剖析基因表达的环境调控
- 批准号:
8786073 - 财政年份:2013
- 资助金额:
$ 61.5万 - 项目类别:
Environmental regulation of gene expression dissected by microfluidics
微流体剖析基因表达的环境调控
- 批准号:
8630064 - 财政年份:2013
- 资助金额:
$ 61.5万 - 项目类别:
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