Although the Mycobacterium avium complex represents a clinically significant group of opportunistic pathogens in AIDS patients, the lack of information regarding their pathogenicity has generated a critical scientific void that makes it difficult to treat infections involving these microorganisms. This problem has gained recent attention in the form of NIH Workshops and Institute Pasteur Forums designed to identify and discuss high-priority areas important in the understanding if these significant opportunistic pathogens. The long-term objective of this research proposal is to form a collaborative effort that will result in a better understanding of three important areas that have been defined for the M. avium complex, pathogenicity, virulence and multiple drug resistance. This will be accomplished by combining the efforts of two laboratories that have studied these mycobacteria throughout the last several years.
Specific aims will be to elucidate the basic mechanisms that define the role of the serovar-specific glycopeptidolipid (GPL) antigens in pathogenicity and to investigate the biosynthesis of the GPL so that specific metabolic targets can eventually be identified to improve antimycobacterial therapy. In addition to the initial six-month visit, two 3-month visits are being requested for the following two year periods. The purpose of these two visits is to complete work that will be started during the initial six-month study. These separate visits will deal primarily with 1) the analysis of new M. avium lipids that will have not been purified in sufficient quantities in time for the first visit and 2) the identification of potential lipid precursors that result from drug inhibitory studies.
| Barrow, W W (1997) Processing of mycobacterial lipids and effects on host responsiveness. Front Biosci 2:d387-400 |
| Barrow, W W; Davis, T L; Wright, E L et al. (1995) Immunomodulatory spectrum of lipids associated with Mycobacterium avium serovar 8. Infect Immun 63:126-33 |
| Rastogi, N; Goh, K S; Wright, E L et al. (1994) Potential drug targets for Mycobacterium avium defined by radiometric drug-inhibitor combination techniques. Antimicrob Agents Chemother 38:2287-95 |
| Barrow, W W; de Sousa, J P; Davis, T L et al. (1993) Immunomodulation of human peripheral blood mononuclear cell functions by defined lipid fractions of Mycobacterium avium. Infect Immun 61:5286-93 |
| Barrow, W W; Wright, E L; Goh, K S et al. (1993) Activities of fluoroquinolone, macrolide, and aminoglycoside drugs combined with inhibitors of glycosylation and fatty acid and peptide biosynthesis against Mycobacterium avium. Antimicrob Agents Chemother 37:652-61 |
