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）代表了一个紧密聚焦、整合和创新的努力，以了解肺炎支原体及其独特的adp核糖化和空泡化毒素的作用，被称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的重要介质，包括新发哮喘和恶化。以及儿童和成人的持续性肺功能障碍。组成SA-AADCRC团队的基础科学和临床研究人员分享广泛的专业知识，并高度合作。SA-AADCRC的广泛攻击策略将基础科学和临床研究项目和核心联系起来。项目1使用小鼠模型和人体材料来解决CARDS TX如何诱发哮喘样疾病和加剧过敏性肺部炎症的基本问题。项目2的重点是识别卡TX adp核糖化气道蛋白靶点，描绘功能重要的卡TX结构域和必需氨基酸，介导卡TX与人表面活性剂蛋白A （SP-A）和气道细胞的结合。并产生阻断/中和CARDS TX的抗体试剂。项目3应用最先进的生物物理技术，通过使用单晶x射线衍射来确定CARDS TX在其辅助因子NAD存在和不存在的情况下的三维结构，揭示CARDS TX的结构和作用；中和单克隆抗体Fab片段；表面活性剂蛋白a （SP-A）。临床核心将从控制良好的哮喘、控制不良的哮喘和健康对照组中收集人体材料，并帮助评估和随访与患者相关的研究。诊断核心将处理临床和实验样本进行诊断分析，为快速检测肺炎支原体TX提供高灵敏度和特异性的诊断分析。病理学核心将提供必要的活检和尸检程序、肺病理解释、组织化学和免疫细胞化学评估，以及定性和半定量的组织病理学分析。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合作。因此，SA-AADCRC代表了一个合作者/同事网络，他们不断提出有关哮喘、气道相关病理、免疫发病机制和肺炎支原体/卡TX生物学和毒力机制的基础和转化问题。

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.