STREPTOCOCCAL INACTIVATOR IN HUMAN CHEMOATTRACTANTS

本项目的主要目标是更好地了解 A组链球菌倾向于 引起人类疾病，并评估新的 发现链球菌补体灭活剂介导的 趋化性，命名为SCP，这个过程。 人类 补体血清蛋白C5 a，主要趋化因子， 炎症过程中，特异性裂解的肽酶 与SCP相关的活动。 本文提出的研究将进一步 定义这种独特的链球菌肽酶的特异性。 一 使用合成肽的生化肽酶测定将是 开发并用于定义基质的决定因素 的特异性 克隆的SCP基因将被测序， 与其他氨基酸序列相比， 链球菌蛋白和其他肽酶，以便 鉴定功能域。 纯化酶的实验 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？ 鼻内 小鼠模型将用于这些实验。 抗体，IgG 和sIgA，能够中和SCP活动将被测试， 可能改变各种链球菌血清型的毒力。 缺乏M疫苗。 这一可能性将由 使用基因工程化的减毒的 携带SCP基因的沙门氏菌菌株 分泌 人类对SCP的免疫反应将由以下定义： 健康人和恢复期患者唾液中抗体的测定 儿童和成人通过ELISA。

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.