STREPTOCOCCAL INACTIVATOR IN HUMAN CHEMOATTRACTANTS

本项目的主要目标是更好地了解 A组链球菌易感的生化基础 引发人类疾病，并评估一种新的 发现补体链球菌灭活剂 趋化性，命名为SCP，对这一过程。人类 补体血清蛋白C5a，主要趋化因子 炎症过程，是由肽酶特异性地分解的 与SCP相关联的活动。这里提出的研究将进一步 确定这种独特的链球菌多肽酶的特异性。一个 使用合成肽的生化多肽酶分析将是 开发并用于定义底物的决定因素 专一性。克隆的SCP基因将被测序，并 推导的氨基酸序列与其他氨基酸序列的比较 链球菌蛋白和其他多肽酶，以便 确定功能域。用纯化的酶进行实验 将评估该因子在链球菌毒力中的作用； 它是否有助于粘膜组织的定植？鼻腔喷雾 这些实验将使用小鼠模型。抗体，免疫球蛋白 和SIgA，能够中和SCP活性将被测试 改变各种链球菌血清型毒力的可能性。 缺乏M疫苗。这种可能性将通过以下方式进行测试 用基因工程减毒活疫苗免疫小鼠 携带scp基因的沙门氏菌。《秘社》 人类对SCP的免疫反应将通过以下方式定义 健康人及康复期患者唾液中抗体的定量检测 儿童和成人用酶联免疫吸附试验。

The primary goal of this project is to better understand the biochemical basis for the propensity of group A streptococci to cause human disease and to evaluate the importance of a newly discovered streptococcal inactivator of complement mediated chemotaxis, designated SCP, to this process. The human complement serum protein C5a, the primary chemotaxin of inflammatory processes, is specifically cleaved by the peptidase activity associated with SCP. Studies proposed here will further define the specificity of this unique streptococcal peptidase. A biochemical peptidase assay employing synthetic peptides will be developed and used to define determinants of substrate specificity. The cloned SCP gene will be sequenced and the deduced amino acid sequence compared to that of other streptococcal proteins, and other peptidases, in order to identify functional domains. Experiments with purified enzyme will evaluate the role of this factor in streptococcal virulence; does it assist colonization of mucosal tissues? An intranasal mouse model will be used for these experiments. Antibody, IgG and sIgA, able to neutralize SCP activity will be tested for the potential to alter virulence of various streptococcal serotypes. The lack of M vaccine. This possibility will be tested by immunization of mice using a genetically engineered, attenuated salmonella strain carrying the SCP gene. The secretory immunological response to SCP in humans will be defined by quantitating antibody in saliva from healthy and convalescent children, and adults by ELISA.