Role of unique ADP-ribosylating vacuolating Mycoplasma pneumoniae toxin i

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) 代表了一项紧密集中、综合和创新的工作，旨在了解肺炎支原体及其独特的 ADP-核糖基化和空泡毒素（指定为社区获得性呼吸窘迫综合征毒素 (CARDS TX)）作为急性和慢性气道疾病（包括新发哮喘和哮喘）的重要介质的作用。儿童和成人的病情加重以及持续性肺功能障碍。 SA-AADCRC 团队的基础科学和临床研究人员拥有广泛的专业知识，并且高度协作。 SA-AADCRC 的广泛攻击战略将基础科学和临床研究项目及核心联系起来。项目 1 使用小鼠模型和人体材料来解决有关 CARDS TX 如何诱发哮喘样疾病并加剧过敏性肺部炎症的基本问题。项目 2 重点是识别 CARDS TX ADP 核糖基化气道蛋白靶点，描绘功能上重要的 CARDS TX 结构域和介导 CARDS TX 与人表面活性蛋白 A (SP-A) 和气道细胞结合的必需氨基酸，并生成阻断/中和 CARDS TX 的抗体试剂。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在其辅因子NAD存在和不存在的情况下的三维结构；中和单克隆抗体Fab片段；和表面活性剂蛋白-A (SP-A)。 Clinical Core将从哮喘控制良好、哮喘控制不佳和健康对照的受试者中收集人体材料，并帮助评估和跟踪患者相关研究。 Diagnostic Core 将通过提供高度灵敏和特异的诊断分析来处理临床和实验样本以进行诊断分析，以快速检测肺炎支原体 CARDS TX。病理学核心将提供必要的活检和尸检程序、肺部病理学解释、组织化学和免疫细胞化学评估以及定性和半定量组织病理学分析。行政核心将监督所有与 SA-AADCRC 相关的活动，并协调项目和核心之间的互动和协作。因此，SA-AADCRC 代表了一个由合作者/同事组成的网络，他们不断提出有关哮喘、气道相关病理学、免疫发病机制以及肺炎支原体/CARDS TX 生物学和毒力机制的基本和转化问题。

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.