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.
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