Biochemical, molecular and immunological characterization of Mycoplasma pneumoni

肺炎支原体是一种常见的非典型细菌性病原体，与急性和 慢性呼吸道疾病，包括新发哮喘和急性发作，以及持续感染， 儿童和成人。知识如何M。肺炎引起感染伴随炎症 途径、病理学和后遗症一直存在缺陷。然而，我们对社区的认同 获得性呼吸窘迫综合征ToXin（TOXin），一种真正的ADP核糖基化和空泡化 毒素，提供了一个直接的因果关系M。肺炎和气道炎症和损伤。这 M之间的联系。肺炎，肺炎克雷伯氏菌和肺高反应性和炎症是 通过SA-AADCRC的研究工作得到加强，证明M. pneumoniae和pneumoniae直接临床 相关性，并进一步得到动物建模和创新的诊断，病理，生物， 化学和免疫学评估。考虑到这些发现以及结构和功能 与百日咳和白喉毒素的相似性和潜在的致病意义，我们 假设MITTX是M.肺炎介导的哮喘， 相关的疾病。为了验证这个假设，我们将：1。表征MTX介导的ADP-核糖基 通过检测ART功能所必需的CARDS TX最小结构域并通过 鉴定被ADTX腺苷二磷酸核糖基化的哺乳动物靶蛋白。2.表征 通过鉴定介导TNF-α的最小区域和必需氨基酸， 与表面活性蛋白-A和哺乳动物细胞受体结合。3.生成单克隆和多克隆 抗HCTTX的抗体，并确定能够诱导HCTTX的表位 阻断/中和抗体。在后一种情况下，中和和中和抗体的抗体试剂的可用性是重要的。 块ESTTX活动，沿着整个SA-AADCRC概述的合作研究 应用应有助于治疗剂的创新设计和改进的诊断。

Mycoplasma pneumoniae is a common atypical bacterial pathogen strongly associated with acute and chronic airway diseases, including new-onset asthma and exacerbations, as well as persistent infections in children and adults. Knowledge on how M. pneumoniae causes infection with accompanying inflammatory pathways, pathologies and sequelae has been deficient. However, our identification of the Community Acquired Respiratory Distress Syndrome ToXin (CARDS TX), a bona fide ADP ribosylating and vacuolating toxin, has provided a direct causal link between M. pneumoniae and ainway inflammation and injury. This connection between M. pneumoniae, CARDS TX and lung hyper-responsiveness and inflammation is reinforced by SA-AADCRC research efforts demonstrating M. pneumoniae and CARDS TX direct clinical relevance and further supported by animal modeling and innovative diagnostic, pathological, biological, chemical and immunological assessments. Considering these findings and the structural and functional similarities and potential pathogenic significance of CARDS TX relative to pertussis and diphtheria toxins, we hypothesize that CARDS TX is a critical pathogenic contributor to M. pneumoniae-mediated asthma and related ainway diseases. To test this hypothesis, we will: 1. Characterize CARDS TX-mediated ADP-ribosyl transferase (ART) activity by detecting the CARDS TX minimal domain essential for ART function and by identifying the mammalian target proteins that are ADP-ribosylated by CARDS TX. 2. Characterize the CARDS TX binding region by identifying the minimal region(s) and essential amino acids that mediate binding to surfactant protein-A and mammalian cell receptor(s). 3. Generate monoclonal and polyclonal antibodies reactive against CARDS TX and determine epitopes of CARDS TX capable of inducing blocking/neutralizing antibodies. In the latter case, the availability of antibody reagents that neutralize and block CARDS TX activities, along with the collaborative studies outlined throughout this SA-AADCRC application should assist in the innovative design of therapeutic agents and improved diagnostics.