Streptococcal Inactivator in Human Chemoattractants

描述（由申请人提供）：本项目旨在了解A群链球菌调节宿主防御的机制。这些链球菌已经进化出包括C5a肽酶在内的蛋白质，该酶可以破坏C5a， C5a是吸引保护性吞噬细胞到感染组织的重要早期信号。最近发现的肽酶也是一种纤维连接蛋白和细胞结合蛋白已成为一个重要的新焦点。实验计划评估这些活性的重要性，相对于肽酶活性在毒力中使用鼻内和皮下小鼠感染模型。认识到青霉素常常不能消除患病儿童喉咙中的A组链球菌，以及最近与链球菌感染相关的严重并发症的重新出现，促使工业界和NIH大力开发预防性疫苗。C5a肽酶是疫苗开发的主要焦点，因此需要更多地了解其在毒力中的作用及其对宿主防御的影响。新的数据表明，C5a肽是链球菌在鼻相关淋巴组织中成功定植和持续存在所必需的。

DESCRIPTION (provided by applicant): This project is an attempt to understand the mechanism by which group A streptococcus modulates host defenses. These streptococci have evolved proteins including the C5a peptidase that destroys C5a, an important early signal that attracts protective phagocytes to infected tissue. The recent discovery that the peptidase is also a fibronectin and cell-binding protein has become a significant new focus. Experiments are planned to evaluate the importance of these activities, relative to peptidase activity in virulence using intranasal and subdermal mouse models of infection. Recognition that penicillin often fails to eliminate group A streptococci from throats of ill children and the recent resurgence of serious complications associated with streptococcal infections, has prompted an intense effort to develop preventive vaccines by industry and NIH. The C5a peptidase is a major focus of vaccine development, increasing the need to learn more about its role in virulence, and its impact on host defenses. New data indicates that the C5a peptide required for successful colonization and persistence of streptococci in nasal associated lymphoid tissue.