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: 8089432
• 负责人: ZEZHANG TOM WEN
• 金额: $ 34.09万
• 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/8089432
• 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; 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 production; 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）：变形链球菌是龋齿的主要病原体，龋齿是世界范围内代价高昂且普遍存在的健康问题。这种生物体引起疾病的能力取决于其粘附在牙齿表面、形成顽强的生物膜以及耐受口腔中的酸和其他有害条件的能力。我们之前表明，生物膜调节蛋白 A (BrpA) 在调节变形链球菌的酸和氧化应激耐受性以及生物膜形成中发挥着重要作用。 BrpA 的缺乏显着增加了缺陷突变体对酸杀伤和过氧化氢挑战的敏感性。 BrpA 缺陷突变体能够在表面结合并形成小菌落，但无法积累和形成成熟的生物膜。 BrpA 被预测为一种表面相关蛋白，是一种糖蛋白，具有口腔菌群中变形链球菌所独有的组成和结构特征。因此，BrpA 作为药物和疫苗生产的候选者具有巨大的潜力，可以消除菌斑中的变形链球菌，而不破坏菌群中的其他有益微生物。本研究旨在进一步研究 BrpA 在以下方面的作用：(i) 细胞定位和结构功能关系，(ii) 响应环境刺激的表达调节，以及 (iii) 在 S.在混合物种生物膜中生长时的变形菌。本研究获得的信息将有助于更好地了解 BrpA 在调节变形链球菌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，从这项研究中获得的数据可以促进治疗和预防策略的设计，以对抗龋齿和可能的感染性心内膜炎。 公众健康相关性：变形链球菌引起龋齿的能力取决于其在牙齿表面粘附并形成顽强生物膜的能力以及耐受口腔中有害条件的能力。变形链球菌中的糖蛋白 BrpA 在环境胁迫耐受和生物膜形成中发挥着重要作用。本研究将进一步研究 BrpA 在调节变形链球菌致病性中的作用和潜在机制，以及在抗龋齿策略中针对 BrpA 的潜力。