Interaction between leukotoxin and RBCs

白细胞毒素和红细胞之间的相互作用

• 批准号: 7847529
• 负责人: SCOTT C KACHLANY
• 金额: $ 19.5万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ DENTAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-22 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847529
• 关键词: Actinobacillus actinomycetemcomitans; Affinity Chromatography; Bacteria; Binding; Blood Cells; Cell Surface Proteins; Cell surface; Cytolysis; Disease; Epitopes; Erythrocytes; Goals; Hemolysis; Human; Human Identifications; Immune response; Immunotoxins; Infection; Infective endocarditis; Lead; Leukocytes; Monoclonal Antibodies; Oral; Pathogenesis; Periodontitis; Play; Primates; Proteins; Role; Systemic disease; Systemic infection; Therapeutic Agents; Toxin; design; leukotoxin; mortality; neutralizing monoclonal antibodies; pathogen; public health relevance; receptor; research study

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.

描述：聚集菌（放线杆菌）放线菌是局部侵袭性牙周炎和其他全身感染（包括感染性心内膜炎）的病原体。 A. actinomycetemcomitans 产生一种 RTX 毒素，即白细胞毒素 (LtxA)，对人类和灵长类动物血细胞具有特异性。 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 可以裂解人红细胞 (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。我们建议首先鉴定 LtxA 的红细胞受体，然后定义参与与红细胞结合的 LtxA 结构域。识别 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随后疾病的治疗药物。公共卫生相关性：口腔和全身病原体，放线菌聚集菌（放线杆菌），会产生一种针对人类血细胞的毒素（白细胞毒素）。关于毒素和红细胞 (RBC) 之间的分子相互作用知之甚少。我们的目标是识别和表征白细胞毒素中的红细胞受体和结构域，这些受体和结构域对于毒素结合红细胞很重要。

项目成果

Broad-spectrum biofilm inhibition by Kingella kingae exopolysaccharide.

Kingella kingae 胞外多糖的广谱生物膜抑制作用。

• 发表时间: 2011-08
• 影响因子: 3.2
• 作者: Bendaoud, Meriem;Vinogradov, Evgeny;Balashova, Nataliya V;Kadouri, Daniel E;Kachlany, Scott C;Kaplan, Jeffrey B
• 通讯作者: Kaplan, Jeffrey B