MOLECULAR MECHANISMS OF MAVIUM COMPLEX PATHOGENESIS

鸟分枝杆菌复合体(MAC)的生物群，它们是 在自然界中无处不在，是最常见的机会性细菌 艾滋病中的病原体。这些生物在群体中表现出多样性。 光滑透明菌落变种占优势的形态 艾滋病患者。HIV感染者通过吞食获得细菌。 和/或吸入导致肠道和肺部定植。 菌落形态与肠道之间的关系已经显示出来。 定植、对上皮细胞的黏附、毒力、抗药性 抗生素、细胞因子和氧自由基的刺激。目的 这项拨款申请的目的是调查MAC的毒力因素 以及与该物种的定植和入侵有关的分子机制 主持人。电子显微镜对粘连动力学的研究 粘膜屏障的穿透及上皮细胞和/或M细胞的作用 将对细胞在MAC发病机制中的作用进行研究。MAC的粘附素 参与结合的菌株和上皮细胞受体 入侵将被识别、隔离和定性。东道主 像细胞因子这样的因素和像阶段这样的寄生虫因素 将对影响发病机制的变异和质粒进行研究。 在表征了粘附素和参与其中的受体之后 宿主-寄生虫相互作用粘附素类似物和/或单抗 将会干扰MAC和MAC之间的交互 上皮细胞。这些调查将有助于了解 MAC的毒力因子、致病机制及对策研究进展 用于预防定植和致病。

Mycobacterium avium complex (MAC) group of organisms, which are ubiquitous in nature, are the most common opportunistic bacterial pathogens seen in AIDS. These organisms exhibit variation in colony morphology with predominance of smooth transparent colony variants in AIDS patients. HIV infected patients acquire the organisms by ingestion and/or inhalation leading to colonization in the intestines and lungs. A relation has been shown between colony morphology and intestinal colonization, adherence to epithelial cells, virulence, resistance to antibiotics, stimulation of cytokines and oxygen radicals. The purpose of this grant application is to investigate the virulence factors of MAC and the molecular mechanisms involved in colonization and invasion of the host. Electron microscopic study of the kinetics of adherence and penetration of the mucosal barrier and the role of epithelial and/or M cells in MAC pathogenesis will be investigated. The adhesins of the MAC strains and the receptors of the epithelial cells involved in the binding and invasion will be identified, isolated and characterized. The host factors like the cytokines and the parasite factors such as phase variation and plasmids influencing the pathogenesis will be studied. After characterization of the adhesins and the receptors involved in the host-parasite interaction adhesin analogues and/or monoclonal antibodies will developed which interfere with the interaction between MAC and epithelial cells. These investigations will help to understand the virulence factors and pathogenesis of MAC, and development of strategies for prevention of colonization and pathogenesis.