BrpA in Virulence Modulation of Streptococcus mutans

BrpA 在变形链球菌毒力调节中的作用

• 批准号: 7741391
• 负责人: ZEZHANG TOM WEN
• 金额: $ 35.5万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7741391
• 关键词: Acids; Adherence; Bacteria; Binding; Data; Dental Plaque; Dental caries; Disease; Drug Delivery Systems; Ecology; Evaluation; Glycoproteins; Goals; Health; Human; Hydrogen Peroxide; Infective endocarditis; Knowledge; Life; Location; Microbial Biofilms; Oral cavity; Organism; Oxidative Stress; Pathogenicity; Play; Predisposition; Prevention strategy; Proteins; Regulation; Role; Stimulus; Streptococcus mutans; Structure-Activity Relationship; Surface; Therapeutic; Vaccine Production; Vaccines; Virulence; assault; combat; design; drug candidate; genetic regulatory protein; killings; microorganism; mutant; oral bacteria; public health relevance; response; stress tolerance; tooth surface; trait

DESCRIPTION (provided by applicant): Streptococcus mutans is the primary etiological agent of dental caries, a costly and ubiquitous health problem worldwide. The ability of this organism to cause disease depends on its abilities to adhere to the tooth surface, form tenacious biofilms and tolerate acid and other detrimental conditions in the oral cavity. We previously showed that the biofilm regulatory protein A (BrpA) plays a major role in regulation of acid- and oxidative-stress tolerance and biofilm formation in S. mutans. Deficiency of BrpA dramatically increased the susceptibility of the deficient mutants to acid-killing and hydrogen peroxide challenge. The BrpA-deficient mutant was able to bind to and form microcolonies on a surface, but failed to accumulate and develop mature biofilms. Predicted as a surface-associated protein, BrpA is a glycoprotein and possesses compositional and structural features that appear to be unique to S. mutans in the oral flora. Therefore, BrpA has great potential as a candidate for drug and vaccine production that may eliminate S. mutans from the plaque without disrupting other beneficial microorganisms in the flora. This study is designed to further investigate BrpA in regards to the (i) cellular location and structure-function relationships, (ii) regulation of expression in response to environmental stimuli, and (iii) role in the adherence, persistence and competitiveness of S. mutans when grown in mixed-species biofilms. The information derived from this study will contribute to a better understanding of the role and the underlying mechanism of BrpA in regulation of S. mutans pathogenicity and will enrich our knowledge on the ecology of the oral flora. More importantly, the data derived from this study could facilitate the design of therapeutic and preventive strategies to combat dental caries and possibly infective endocarditis. PUBLIC HEALTH RELEVANCE: The ability of Streptococcus mutans to cause dental caries depends on its ability to adhere to and form tenacious biofilms on the tooth surface and to tolerate detrimental conditions in the oral cavity. Glycoprotein BrpA in S. mutans plays major roles in environmental stress tolerance and formation of biofilms. This study will further investigate the role and the underlying mechanisms of BrpA in regulation of S. mutans pathogenicity and the potential for targeting BrpA in anti-caries strategy.

描述（由申请人提供）：链球菌突变是龋齿的主要病因学药，这是全球昂贵且无处不在的健康问题。这种生物引起疾病的能力取决于其粘附在牙齿表面，顽强的生物膜并耐受酸以及口腔中其他有害条件的能力。我们先前表明，生物膜调节蛋白A（BRPA）在调节S. utans中的酸和氧化压力耐受性和生物膜形成中起主要作用。 BRPA的缺乏症显着增加了缺乏突变体对杀死酸和过氧化氢挑战的敏感性。缺乏BRPA的突变体能够在表面上结合并形成微菌落，但未能积累和发展成熟的生物膜。 BRPA被预测为与表面相关的蛋白质，是一种糖蛋白，具有口服菌群中突变体独有的成分和结构特征。因此，BRPA作为药物和疫苗生产的候选者具有巨大的潜力，可以从斑块中消除S. utans，而不会破坏菌群中其他有益的微生物。这项研究旨在进一步研究（i）细胞位置和结构 - 功能关系，（ii）对环境刺激的响应表达的调节，以及（iii）在混合物种生物膜中生长时繁殖体的依从性，持久性和竞争力的作用。从这项研究中得出的信息将有助于更好地理解BRPA在调节S. mutans的致病性中的作用和潜在机制，并将丰富我们对口腔菌群生态学的了解。更重要的是，从这项研究中得出的数据可以促进设计治疗和预防性策略，以打击龋齿和可能的感染性心内膜炎。 公共卫生相关性：链球菌突变引起龋齿的能力取决于其在牙齿表面粘附并形成顽强的生物膜并耐受口腔中有害条件的能力。链球菌中的糖蛋白BRPA在环境胁迫耐受性和生物膜的形成中起主要作用。这项研究将进一步研究BRPA在调节链球菌致病性调节中的作用和潜在机制，以及在抗辣椒策略中靶向BRPA的潜力。