BrpA in Virulence Modulation of Streptococcus mutans

描述（由申请人提供）：变形链球菌是龋齿的主要病原体，龋齿是全球范围内普遍存在的昂贵健康问题。这种微生物引起疾病的能力取决于其粘附在牙齿表面、形成坚韧的生物膜以及耐受口腔中的酸和其他有害条件的能力。我们以前的研究表明，生物膜调节蛋白A（BrpA）在调节S.变异人BrpA的缺陷显着增加了缺陷突变体的敏感性，以酸杀死和过氧化氢的挑战。BrpA缺陷突变体能够结合并在表面上形成小菌落，但未能积累和发育成熟的生物膜。作为一种表面结合蛋白，BrpA是一种糖蛋白，具有似乎是唯一的S.口腔植物群中的变异株。因此，BrpA具有很大的潜力，可以作为药物和疫苗生产的候选人，可能会消除S。从牙菌斑中清除变形菌而不破坏植物群中的其它有益微生物。本研究旨在进一步研究BrpA在（i）细胞定位和结构-功能关系，（ii）响应环境刺激的表达调控，以及（iii）在S.当在混合物种生物膜中生长时，本研究为深入了解BrpA在S.变异株致病性的研究，将丰富我们对口腔植物群生态学的认识。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。 公共卫生相关性：变形链球菌引起龋齿的能力取决于其粘附于牙齿表面并在牙齿表面上形成坚韧生物膜的能力以及耐受口腔中的有害条件的能力。S.变形杆菌在环境胁迫耐受和生物膜形成中起主要作用。本研究将进一步探讨BrpA在S.变形菌的致病性和在抗龋策略中靶向BrpA的潜力。

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.