Role of unique ADP-ribosylating vacuolating Mycoplasma pneumoniae toxin i

独特的 ADP-核糖基化空泡肺炎支原体毒素 i 的作用

• 批准号: 8300811
• 负责人: JOEL Barry BASEMAN
• 金额: $ 203.36万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8300811
• 关键词: Acute; Address; Adult; Allergic; Allergic Disease; Antibodies; Asthma; Autopsy; Basic Science; Binding; Biological Assay; Biology; Biopsy; Cells; Child; Chronic; Clinical; Clinical Investigator; Clinical Research; Collaborations; Commit; Community Acquired Respiratory Distress Syndrome Toxin; Development; Diagnostic; Disease; Doctor of Philosophy; Essential Amino Acids; Evaluation; Fab Immunoglobulins; Fertilization; Functional disorder; Goals; Health; Human; Inflammation; Injury; Lead; Link; Lung; Lung diseases; Mediating; Mediator of activation protein; Modeling; Mus; Mycoplasma pneumoniae; Pathologic; Pathology; Patients; Pneumonia; Postdoctoral Fellow; Prevention; Procedures; Process; Proteins; Pulmonary Surfactant-Associated Protein A; Qualitative Evaluations; Reagent; Research; Research Project Grants; Resources; Role; Sampling; Structure; Techniques; Testing; Time; Toxin; Virulence; Virulence Factors; X ray diffraction analysis; X-Ray Diffraction; airway inflammation; clinical material; cofactor; follow-up; graduate student; injured airway; innovation; neutralizing monoclonal antibodies; novel diagnostics; novel therapeutics; rapid detection; success; therapeutic vaccine; three dimensional structure

DESCRIPTION (provided by applicant): The San Antonio Asthma and Allergic Diseases Cooperative Research Center (SA-AADCRC) represents a tightly focused, integrative and innovative effort to understand the role of Mycoplasma pneumoniae and its unique ADP-ribosylating and vacuolating toxin, designated Community Acquired Respiratory Distress Syndrome ToXin (CARDS TX) as important mediators of acute and chronic airway diseases, including new onset asthma and exacerbations, as well as persistent pulmonary dysfunction in children and adults. The basic science and clinical investigators who comprise the SA-AADCRC team share broad expertise and are highly collaborative. The SA-AADCRC's broad strategy of attack interlinks basic science and clinical research projects and cores. Project 1 uses the murine model and human materials to address fundamental questions on how CARDS TX induces asthma-like disease and exacerbates allergic pulmonary inflammation. Project 2 focuses on identifying CARDS TX ADP-ribosylating airway protein targets, delineating functionally important CARDS TX domains and essential amino acids that mediate CARDS TX binding to human surfactant protein A (SP-A) and airway cells, and generating antibody reagents that block/neutralize CARDS TX. Project 3 applies state-of-the-art biophysical techniques to uncover the structure and action of CARDS TX by using single crystal X-ray diffraction to determine CARDS TX three dimensional structure in the presence and absence of its cofactor NAD; neutralizing monoclonal antibody Fab fragments; and surfactant protein-A (SP-A). Clinical Core will collect human material from subjects with well controlled asthma, poorly controlled asthma and healthy controls and help in evaluation and follow-up of patient-related studies. Diagnostic Core will process clinical and experimental samples for diagnostic analysis by providing highly sensitive and specific diagnostic assays for rapid detection of M. pneumoniae CARDS TX. Pathology Core will provide necessary biopsy and necropsy procedures, lung pathology interpretation, histochemical and immunocytochemical evaluations, and qualitative and semiquantitative histopathologicai analyses. Administrative Core will oversee all SA-AADCRC-related activities and coordinate interactions and collaborations between projects and cores. Therefore, the SA-AADCRC represents a network of collaborators/colleagues who continuously ask fundamental and translational questions about asthma, airway-related pathologies, immunopathogenesis, and M. pneumoniae/CARDS TX biology and virulence mechanisms.

描述（由申请人提供）：圣安东尼奥哮喘和过敏性疾病合作研究中心（SA-AADCRC）代表着紧密集中，集成和创新的努力，以了解肺炎肺炎的作用及其独特的ADP-核糖基化和吸收型毒性的互联性（Chards Issiirations orderication orderication orderonics ordornication），气道疾病，包括新的哮喘和恶化，以及儿童和成人的持续性肺部功能障碍。组成SA-AADCRC团队的基础科学和临床研究人员具有广泛的专业知识，并且是高度协作的。 SA-AADCRC的广泛攻击战略将基础科学与临床研究项目和核心互动。项目1使用鼠模型和人类材料来解决有关卡TX如何诱导哮喘疾病并加剧过敏性肺部炎症的基本问题。项目2专注于识别卡片TX ADP-核糖基气道蛋白靶标，划定功能重要的卡TX结构域和必需的氨基酸，这些氨基酸介导了卡片TX TX结合与人表面活性剂蛋白A（SP-A）和气道细胞的结合，以及产生抗体试剂，以阻止/中和卡片。项目3应用最先进的生物物理技术来揭示Cards TX的结构和作用，通过使用单晶X射线衍射来确定Cards TX TX TX TX三维结构，在存在和不存在其辅助因子NAD的情况下；中和单克隆抗体Fab片段；和表面活性剂蛋白A（SP-A）。临床核心将从具有良好控制哮喘，控制良好的哮喘和健康对照的受试者那里收集人类物质，并有助于评估和随访与患者有关的研究。诊断核心将通过提供高度敏感和特定的诊断测定法以快速检测到肺炎支原体卡TX来处理临床和实验样本进行诊断分析。病理核心将提供必要的活检和尸检程序，肺病理学解释，组织化学和免疫细胞化学评估，以及定性和半毒性组织病理学分析。行政核心将监督所有与SA-AADCRC相关的活动，并协调项目与核心之间的互动和协作。因此，SA-AADCRC代表了一个合作者/同事的网络，他们不断提出有关哮喘，与气道相关的病理，免疫病变以及肺炎M.肺炎/卡片TX生物学和毒力机制的基本和翻译问题。