Interaction between leukotoxin and RBCs

描述：伴放线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其他全身感染的病原体。伴生放线菌产生一种RTX毒素，即白毒素(LtxA)，专用于人类和灵长类血细胞。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具有裂解人红细胞(RBC)的功能，并表明这一新功能可能在发病机制中发挥重要作用。由于我们只是最近才观察到这一点，因此几乎对LtxA和红细胞之间的相互作用一无所知。拟议的实验旨在描述和定义LtxA和红细胞之间的分子相互作用。我们建议首先确定LotxA的RBC受体，然后定义与RBC结合的LotxA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设计出阻止相互作用和后续疾病的治疗剂。公共卫生相关性：口腔和全身病原体Aggregatibater(放线杆菌)伴生放线菌产生一种针对人类血细胞的毒素(白毒素)。人们对这种毒素与红细胞之间的分子相互作用知之甚少。我们的目标是识别和表征白血球毒素中的RBC受体和结构域，这些区域对于白血球毒素结合红血球非常重要。

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.