MOLECULAR MECHANISMS OF MAVIUM COMPLEX PATHOGENESIS

MAVIUM 复杂发病的分子机制

• 批准号: 6169335
• 负责人: VENKATA M REDDY
• 金额: $ 10.77万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6169335
• 关键词: Mycobacterium avium; adhesin; electron microscopy; epithelium; host organism interaction; infection; laboratory mouse; monoclonal antibody; pathologic process; receptor; tissue /cell culture; virulence

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.

分枝杆菌鸟类综合体（MAC）的生物群， 本质上无处不在，是最常见的机会细菌 在艾滋病中看到的病原体。 这些生物在菌落中表现出差异 形态学以平滑透明菌落变体优势 艾滋病患者。 艾滋病毒感染的患者通过摄取获得生物 和/或吸入导致肠道和肺部定植。 菌落形态和肠道之间已经显示了关系 定殖，遵守上皮细胞，毒力，抗性 抗生素，细胞因子和氧自由基的刺激。 目的 该赠款的应用是研究MAC的毒力因子 以及涉及定植和侵袭的分子机制 主持人。 电子微观研究的依从性动力学和 粘膜屏障的穿透以及上皮和/或M的作用 将研究MAC发病机理中的细胞。 Mac的粘合剂 菌株和与结合的上皮细胞的受体 将确定，孤立和表征入侵。 主人 诸如细胞因子和寄生虫因子（例如相）等因素 将研究影响发病机理的变异和质粒。 在表征粘合剂和涉及的受体之后 宿主 - 寄生虫相互作用类似物和/或单克隆抗体 将开发出干扰Mac和Mac之间的相互作用的 上皮细胞。 这些调查将有助于了解 MAC的毒力因素和发病机理以及策略的发展 用于预防定植和发病机理。