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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：
10175495
负责人：
Robert A Burne
金额：
$ 21.53万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10175495
关键词：
2019-nCoV Adhesions Affinity Animals Antigens Antiviral Agents Area Arginine Award Bacteria Binding Biological COVID-19 Clinical Clinical Trials Collaborations Collection Dental caries Detection Enzymes Etiology Formulation Foundations Generations Genetic Genetic Markers Genomics Health Human Hydrogen Peroxide Immunologics In Vitro Individual International Intervention Lead Mediating Membrane Proteins Metabolic Metabolism Methods Microbial Biofilms Modeling Monitor Morbidity - disease rate Mus Nasopharynx Oral Oral cavity Oral health Oxidases Parents Peptide Hydrolases Phenotype Positioning Attribute Probiotics Property Proteins Reagent Respiratory Tract Infections Rodent Model Severities Source Streptococcus Streptococcus mutans Surface System Testing Translating Viral Viral Pathogenesis Virulence Virus Virus Diseases Virus Receptors bacteriocin commensal bacteria comparative genomics dental biofilm functional genomics gene product human tissue in vivo macromolecule member metatranscriptomics microbiome mortality mouse model mutant novel novel therapeutics oral commensal oral pathogen oral streptococci oral tissue overexpression pathogen prevent probiotic therapy receptor soft tissue

项目摘要

Abstract/Summary Commensal oral streptococci are the most abundant bacteria in the biofilms that colonize the hard and soft tissues of the human oral cavity and many areas of the nasopharynx. These health-associated bacteria employ multiple diverse adhesion strategies and produce a spectrum of compounds and macromolecules that inhibit the colonization and virulence of pathogens. With support from R01 DE25832, a large collection of commensal oral streptococci has been isolated from healthy subjects, then characterized at the phenotypic and genomic levels for properties that may promote oral and systemic health. Here, we propose to screen these highly diverse strains for their ability to bind to and degrade purified SARS-CoV-2 surface proteins and to interfere with CoV-2 Spike protein engagement of the viral receptor, ACE2. Standard methods will then be used to identify the streptococcal gene products that mediate inhibitory activities. Defined mutants and overexpressing strains will be utilized to confirm the results. Though not a focus of this Urgent Revision application, it is noteworthy that, as part of DE25832, we have developed a mouse model in which we can establish various commensal streptococci in the oral cavity, then challenge the commensal-colonized mice with a pathogen(s). Such a model could be adapted to in vivo animal challenge studies. Importantly, novel systems for formulation and delivery of one of our commensal strains have already been optimized through an international collaboration, and thus we are well positioned to rapidly translate our in vitro findings to clinical trials of a therapeutic probiotic intervention.

摘要/概要共生口腔链球菌是最丰富的细菌在生物膜殖民的硬和软人口腔和鼻咽的许多区域的组织。这些与健康相关的细菌多种多样的粘附策略，并产生一系列化合物和大分子，病原体的定植和毒性。在R 01 DE 25832的支持下，口腔链球菌已从健康受试者中分离出来，然后在表型和基因组上进行表征。可能促进口腔和全身健康的性质的水平。在这里，我们建议高度筛选这些不同菌株能够结合和降解纯化的SARS-CoV-2表面蛋白并干扰与病毒受体ACE 2的CoV-2刺突蛋白接合。标准方法将用于鉴定介导抑制活性的链球菌基因产物。确定的突变体和过表达将使用菌株来确认结果。虽然不是这个紧急修订申请的重点，但它是值得注意的是，作为DE 25832的一部分，我们已经开发了一种小鼠模型，其中我们可以建立各种在口腔中的细菌链球菌，然后用病原体攻击细菌定殖的小鼠。这样的模型可以适用于体内动物攻击研究。重要的是，用于配制的新系统和交付我们的一种海藻菌株已经通过一个国际合作，因此，我们处于有利地位，可以迅速将我们的体外研究结果转化为临床试验，益生菌治疗干预。