MYCOPLASMA PNEUMONIAE: AIRWAY INTERPLAY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。人体呼吸系统空气空间的上皮层提供了吸入气体和肺血流之间的重要屏障。由于其大的表面积，脆弱的膜和解剖位置，上皮屏障很容易受到吸入有毒物质的破坏和感染因子的攻击。无细胞壁细菌，肺炎支原体（其基因组已完全测序），是人类呼吸道常见的细菌病原体。它引起一系列急性和慢性疾病，包括气管支气管炎、肺炎和其他气道病变，以及肺外表现，如关节、中枢神经系统和心血管受累。这种微生物呈瓶状，通过独特的尖端状末端细胞器附着在呼吸细胞表面。一般来说，细菌粘附是一个复杂的过程，涉及微生物与靶细胞之间的多重相互作用和分子串扰。我们一直在研究肺炎支原体和其他支原体的细胞粘附机制，我们最近的研究表明，气道微环境中的各种成分有助于支原体-呼吸细胞相互作用和随后的组织定植。描述这些环境成分在支原体，特别是肺炎支原体感染过程中的作用是本提案的主要目标。我们将重点了解纤维连接蛋白（FN）和表面活性剂蛋白A （SP-A）如何影响支原体-气道细胞的相互作用，因为这些宿主蛋白在呼吸道中大量存在。这些蛋白发挥多种作用，包括i)调节肺泡巨噬细胞增强对入侵细菌的吞噬；ii)协助细菌（特别是FN）与非吞噬细胞结合。我们已经发现肺炎支原体中存在FN-和SP-A结合蛋白，我们打算阐明这些蛋白作为支原体-气道细胞相互作用的介质的作用。因此，该研究有望提供关于支原体寄生机制的新见解，连同现有的关于支原体细胞粘附的知识基础，将拓宽我们对支原体发病机制和毒力决定因素的整体理解。最终，这些研究应该确定新的治疗策略来控制人类支原体感染。

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. The epithelial lining of air spaces of the human respiratory system provides a crucial barrier between inspired gas and pulmonary blood flow. By virtue of its large surface area, delicate membranes and anatomic location, the epithelial barrier is vulnerable to damage by inhaled toxic substances and attack by infectious agents. The cell wall-less bacterium, Mycoplasma pneumoniae (whose genome is completely sequenced), is a common bacterial pathogen of the human respiratory tract. It causes a range of acute and chronic illnesses, including tracheobronchitis, pneumonia and other airway pathologies as well as extrapulmonary manifestations, such as joint, CNS and cardiovascular involvement. This microorganism exhibits a flask-like appearance and adheres to respiratory cell surfaces via a unique tip-like terminal organelle. In general, bacterial adherence is a complex process involving multiple interactions and molecular cross-talk between the microbe and target cell. We have been investigating mechanisms of cytadherence of M. pneumoniae and other mycoplasmas, and our recent studies indicate that various components in the airway microenvironment contribute to mycoplasma-respiratory cell interactions and subsequent tissue colonization. Delineating the role of such environmental components in the infectious process of mycoplasmas, particularly M. pneumoniae, is a major objective of this proposal. We will focus on understanding how fibronectin (FN) and surfactant protein A (SP-A) influence the mycoplasma-airway cell interplay, as these host proteins exist abundantly in the respiratory tract. These proteins play several roles including i) modulating alveolar macrophages in enhanced phagocytosis of invading bacteria; and ii) assisting bacteria (particularly FN) in binding to non-phagocytic cells. We have discovered the presence of FN- and SP-A binding proteins in M. pneumoniae, and we intend to clarify the role of these proteins as mediators of mycoplasma- airway cell interactions. Thus, the proposed study is expected to provide new insights concerning mycoplasma parasitic mechanisms which, together with the existing knowledge base concerning mycoplasma cytadherence, will broaden our overall understanding of mycoplasma pathogenesis and virulence determinants. Ultimately, these studies should identify new therapeutic strategies to control mycoplasma infections in humans.