MOLECULAR MECHANISMS OF MAVIUM COMPLEX PATHOGENESIS

鸟分枝杆菌复合群（MAC）微生物， 在自然界中普遍存在，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变异 形态以光滑透明菌落变体为主， 艾滋病患者。 艾滋病病毒感染者通过摄入获得该生物体 和/或吸入导致肠和肺中的定殖。 菌落形态与肠道菌群之间存在一定的关系， 定植，粘附上皮细胞，毒力，耐药性， 抗生素、细胞因子和氧自由基的刺激。 目的 本基金申请的主要目的是研究MAC的毒力因子 以及参与定植和入侵的分子机制 主持人 粘附动力学的电镜研究， 粘膜屏障的穿透以及上皮和/或M 细胞在MAC发病机制将进行研究。 MAC的粘附素 菌株和参与结合的上皮细胞的受体 和入侵将被识别、隔离和表征。 主机 因子如细胞因子和寄生虫因子， 将研究影响发病机制的变异和质粒。 在表征了参与粘附的粘附素和受体之后， 宿主-寄生虫相互作用粘附素类似物和/或单克隆抗体 将开发干扰MAC和 上皮细胞 这些调查将有助于了解 MAC的毒力因子和致病机制，以及发展策略 以防止定植和发病。

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.