MECHANISMS OF HOST RESISTANCE OF GROUP B STREPTOCOCCI

B群链球菌(GBS)是引起严重 新生儿、怀孕女性和其他人群的发病率和死亡率 免疫功能受损的宿主。在之前的研究中，我们已经表明 纤维连接蛋白(FN)增强抗体包被的GBS的吞噬功能 并在新生儿体内提供对这些微生物的保护作用 大鼠模型。目前的调查将研究这一机制。 FN的作用通过确定细胞结合氨基酸是否 分子的序列RGDS对这种效应负责。这些 将是第一次研究这种四肽在 对微生物病原体的保护和第一个检查其 在活体中的作用。我们认为新生儿GBS的最佳免疫治疗方案 疾病可能涉及FN或多价RGDS的给药 B组链球菌的配基和抗体。 我们已经描述了大多数的酶活性 能灭活细菌趋化活性的GBS菌株 来自补体系统的主要化学诱导剂，C5a。 GBS C5a-酶切割7个残基，约650kD片段 从分子的羧基末端，防止它 与吞噬细胞结合。我们计划将这种酶提纯到 同质性，产生多克隆和单克隆抗体 探讨其在GBS感染的炎症反应中的作用 一个动物模型。具有使C5a明显失活的特性的酶 具有，A纯化的潜力，可用于额外的实验和 治疗应用。

Group B streptococci(GBS) are a major cause of serious morbidity and mortality in neonates, pregnant females and other immunocompromised hosts. In previous studies we have shown that fibronectin(FN) enhances phagocytic uptake of antibody coated GBS and offers protective activity against these organisms in a neonatal rat model. The present investigations will examine the mechanism of FN's effect by determining if the cell binding amino acid sequence RGDS of the molecule is responsible for this effect. These will be the first studies on the role of this tetrapeptide in protection against a microbial pathogen and the first to examine its role in vivo. We believe that optimal immunotherapy of neonatal GBS disease may involve the administration of FN or a multivalent RGDS ligand along with antibody to the group B streptococcus. We have described an enzymatic activity on the majority of strains of GBS that inactivates the chemotactic activity of the major chemoattractant derived from the complement system, C5a. The GBS C5a-ase cleaves a 7 residue, approximately 650 kD fragment from the carboxy terminal of the molecule which prevents it from binding to phagocytic cells. We plan to purify this enzyme to homogeneity, produce polyclonal and monoclonal antibodies to it and examine its role in the inflammatory response to GBS infection in an animal model. characterized enzyme that inactivates C5a clearly has the, A purified potential for additional experimental and therapeutic applications.