Interaction between leukotoxin and RBCs

产品说明：伴放线杆菌是局部侵袭性牙周炎和包括感染性心内膜炎在内的全身性感染的病原体。A.伴随放线菌产生RTX毒素，白细胞毒素（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。事实上，我们对LtxA和RBC之间的相互作用一无所知，因为我们最近才进行了这一观察。所提出的实验旨在表征和定义LtxA和RBC之间的分子相互作用。我们建议首先确定LtxA的RBC受体，然后定义参与与RBC结合的LtxA结构域。确定LtxA和宿主RBC之间的关键相互作用可能导致设计阻断相互作用和随后疾病的治疗剂。公共卫生相关性：口腔和全身病原体，Aggregatibater（放线杆菌）放线菌，产生一种毒素（白细胞毒素），目标是人类血细胞。关于毒素和红细胞（RBC）之间的分子相互作用知之甚少。我们的目标是确定和表征红细胞受体和结构域的白细胞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.