Interaction between leukotoxin and RBCs

描述：放线菌群是局部侵袭性牙周炎和其他全身性感染（包括感染性心内膜炎）的病因。放线菌（actinomycetemcomitans）产生一种RTX毒素，白毒素（LtxA），对人类和灵长类动物的血细胞具有特异性。LtxA作为一种免疫毒素，帮助细菌逃避免疫反应。我们最近发现LtxA可以溶解人红细胞（rbc），并表明这种新功能可能在发病机制中发挥重要作用。实际上，我们对LtxA和红细胞之间的相互作用一无所知，因为我们最近才观察到这一点。提出的实验旨在表征和定义LtxA和红细胞之间的分子相互作用。我们建议首先确定LtxA的红细胞受体，然后确定LtxA与红细胞结合的结构域。确定LtxA和宿主红细胞之间的关键相互作用可能会导致治疗药物的设计，以阻止相互作用和随后的疾病。公共卫生相关性：口腔和全身病原体放线菌（放线菌）产生一种针对人体血细胞的毒素（白毒素）。关于毒素与红细胞（rbc）之间的分子相互作用知之甚少。我们的目标是鉴定和表征红细胞受体和结构域在白毒素是重要的毒素结合红细胞。

DESCRIPTION: Aggregatibater (Actinobacillus) actinomycetemcomitans is the etiologic agent of localized aggressive periodontitis and other systemic infections including infective endocarditis. A. actinomycetemcomitans produces an RTX toxin, leukotoxin (LtxA), specific for human and primate blood cells. LtxA acts as an immunotoxin, helping the bacterium to evade the immune response. We recently discovered that LtxA can lyse human red blood cells (RBCs) and have shown that this new function may play an important role in pathogenesis. Virtually nothing is known about the interactions between LtxA and RBCs since we only recently made this observation. The proposed experiments are designed to characterize and define the molecular interactions between LtxA and RBCs. We propose to first identify the RBC receptor for LtxA and next to define the domains of LtxA that are involved in binding to RBCs. Identifying critical interactions between LtxA and host RBCs may lead to the design of therapeutic agents that block interaction and subsequent disease. PUBLIC HEALTH RELEVANCE: The oral and systemic pathogen, Aggregatibater (Actinobacillus) actinomycetemcomitans, produces a toxin (leukotoxin) that targets human blood cells. Very little is known about the molecular interactions between the toxin and red blood cells (RBCs). Our goals are to identify and characterize the RBC receptor and domains in leukotoxin that are important for the toxin to bind RBCs.