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MOLECULAR MECHANISMS OF MAVIUM COMPLEX PATHOGENESIS

MAVIUM 复杂发病的分子机制

基本信息

批准号：
6373511
负责人：
VENKATA M REDDY
金额：
$ 11.08万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-05-01 至 2004-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6373511
关键词：
Mycobacterium avium adhesin electron microscopy epithelium host organism interaction infection laboratory mouse monoclonal antibody pathologic process receptor tissue /cell culture virulence

项目摘要

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.

鸟分枝杆菌复合体 (MAC) 群生物体，它们是自然界中普遍存在，是最常见的机会性细菌艾滋病中常见的病原体。这些生物在群体中表现出变异形态以光滑透明的菌落变体为主艾滋病患者。 HIV感染者通过摄入获得微生物和/或吸入导致在肠和肺中定植。菌落形态与肠道之间存在关系。定植、粘附于上皮细胞、毒力、抗性抗生素、细胞因子和氧自由基的刺激。目的本次拨款申请的目的是研究 MAC 的毒力因子以及参与定植和侵袭的分子机制主持人。粘附动力学的电子显微镜研究粘膜屏障的穿透性以及上皮细胞和/或 M 的作用 MAC 发病机制中的细胞将被研究。 MAC 的粘附素菌株和参与结合的上皮细胞受体入侵将被识别、隔离和表征。主人细胞因子等因素和相位等寄生虫因素将研究影响发病机制的变异和质粒。在对参与的粘附素和受体进行表征后宿主-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 和之间的交互上皮细胞。这些调查将有助于了解 MAC毒力因子、发病机制及策略制定用于预防定植和发病机制。