STRUCTURAL CHARACTERIZATION OF PROTEINS INVOLVED IN HOST/PATHOGEN INTERACTIONS A

参与宿主/病原体相互作用的蛋白质的结构特征 A

• 批准号: 8170284
• 负责人: Martin J Boulanger
• 金额: $ 0.07万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170284
• 关键词: 5 year old; Acute; Adult; Antibiotic Resistance; Antigens; Autacoids; Bacteria; Bacterial Adhesins; Binding; Cause of Death; Cells; Child; Communities; Computer Retrieval of Information on Scientific Projects Database; Elderly; Family; Frequencies; Funding; Glycoside Hydrolases; Goals; Gram-Positive Bacteria; Grant; Healthcare Systems; Infection; Institution; Invaded; Lung diseases; Mediating; Membrane Proteins; Meningitis; Molecular; Otitis Media; Parasites; Pneumonia; Population; Proteins; Research; Research Personnel; Resources; Septicemia; Source; Streptococcus pneumoniae; Therapeutic Intervention; Toxoplasma gondii; United States National Institutes of Health; Vaccines; Viral; Work; base; design; fighting; inhibitor/antagonist; member; pathogen; prophylactic; small molecule; vigilance

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1) The protozoan parasite Toxoplasma gondii is a serious global pathogen that infects nearly one third of the adult human population. Despite its importance, very little is known about how this parasite initially engages a host cell in order to establish infection. The aim of this proposal is to characterize the molecular interactions that enable T. gondii to attach to, and ultimately invade virtually every nucleated cell. More specifically, we will characterize the structural basis of how key members of a superfamily of developmentally expressed surface proteins on T. gondii (known as the SRS adhesins/antigens) mediate parasite attachment to host cells. Based on this work, we will be strategically poised to develop therapeutic interventions, either prophylactic or vaccine-based, to limit infectivity of this widespread zoonotic pathogen. 2)Pneumonia is an acute respiratory disease that is caused by viral or bacterial pathogens. The major causative agent, however, is the Gram positive bacterium Streptococcus pneumoniae. Invasive S. pneumoniae infections are a leading cause of death world-wide, with the hardest hit being the elderly and children less than 5 years old. In addition to pneumonia, this bacterium can cause meningitis, septicaemia, and otitis media. S. pneumoniae is clearly a serious pathogen that places a considerable burden on healthcare systems. Disturbingly, the frequency of antibiotic resistance in community acquired strains of S. pneumoniae is increasing requiring increased vigilance and redoubled research efforts aimed at fighting this bacterium. Our goal is to define the molecular mechanism of a family of S. pneumoniae encoded glycoside hydrolases with the ultimate goal of designing small molecule inhibitors.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 1）原生动物寄生虫弓形虫是一种严重的全球病原体，可感染近三分之一的成年人人口。尽管它很重要，但对于该寄生虫最初如何使宿主细胞与建立感染相关的知识知之甚少。该提议的目的是表征使T. gondii能够附着并最终侵入几乎所有核定细胞的分子相互作用。更具体地说，我们将表征gondii（称为SRS粘附素/抗原）上发育表达的表面蛋白的主要成员如何介导寄生虫附着在宿主细胞上的结构基础。基于这项工作，我们将在战略上准备开发预防性或基于疫苗的治疗性干预措施，以限制这种广泛的人畜共患病原体的感染性。 2）肺炎是由病毒或细菌病原体引起的急性呼吸道疾病。然而，主要的致病剂是革兰氏阴性链球菌肺炎的阳性。侵入性的肺炎链球菌感染是全球死亡的主要原因，最受欢迎的是老年人和不到5岁的儿童。除肺炎外，该细菌还会引起脑膜炎，败血病和中耳炎。肺炎链球菌显然是一种严重的病原体，对医疗保健系统造成了巨大负担。令人不安的是，社区获得的肺炎链球菌菌株中抗生素耐药性的频率正在增加，需要提高警惕性和旨在抵抗该细菌的研究工作。我们的目标是定义肺炎链球菌家族编码糖苷水解酶的分子机制，其最终目标是设计小分子抑制剂。