Mycobacterium avium is an acid-fast bacterium that is ubiquitous in nature; it infects many humans and causes disease in certain individuals. Most patients with disease caused by M. avium have some other underlying disease, such as acquired immunodeficiency syndrome (AIDS). The mycobacterial disease is difficult to treat because of the microbe's innate drug resistance. Certain features most closely associated with the growth and division of M. avium include metabolic and enzyme activities that differ from those found in eucaryote cells, such as host macrophages. The long-term goal is to identify those drugs that will be toxic for M. avium and yet nontoxic for macrophages. The specific aims of this project are to determine the in vitro susceptibility of M. avium to antimetabolites that interfere with lipid, nitrogen, and nucleic acid metabolism. The drugs will be tested individually, and in combination, against M. avium in a defined medium that lacks albumin. Effect on the growth of the bacterium will be determined by turbidity, viability, and isotope incorporation measurements. The concentration of drugs added to the medium will be monitored by chemical and bioassay procedures to ensure that they are not inactivated by the culture conditions. Those drugs or combinations that have activity against M. avium will be tested for nontoxicity to macrophages cultured in vitro.