BrpA in Virulence Modulation of Streptococcus mutans

总结： 变形链球菌是龋齿的主要病原体，龋齿是一种昂贵且普遍存在的健康问题 全世界的问题。这种微生物致病的能力取决于它粘附在微生物表面的能力。 牙齿表面，形成坚韧的生物膜，并耐受口腔中的酸和其他有害条件。 我们以前表明，生物膜调节蛋白A（BrpA）在调节酸性蛋白中起着重要作用。 以及氧化胁迫耐受性和生物膜形成。变异人BrpA缺乏症 增加了缺陷突变体对酸杀伤和过氧化氢挑战的敏感性。的 BrpA缺陷突变体能够结合并在表面上形成小菌落，但不能积累 形成成熟的生物膜预测为表面相关蛋白，BrpA是糖蛋白， 具有似乎是S所独有的成分和结构特征。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-功能方面的作用 关系，（ii）响应环境刺激的表达调节，以及（iii）在 S.当在混合物种生物膜中生长时，的 从这项研究中获得的信息将有助于更好地理解的作用和基本的 BrpA对S.变形菌的致病性，并将丰富我们的知识，生态 口腔植物群。更重要的是，从这项研究中获得的数据可以促进 防治龋齿和可能的感染性心内膜炎的治疗和预防战略。

SUMMARY: 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.