A major clinical problem in infectious diseases in the United States is the recognition, diagnosis, control, and treatment of serious, life-threatening infections in immunocompromised individuals. Many patients with treatable underlying illnesses succumb to opportunistic pathogens before the patient's original problem can be controlled. Nocardia asteroides, a normal inhabitant of the soil, is an important opportunistic pathogen that frequently causes serious pulmonary and systemic infections in compromised patients. Little is known concerning the precise mechanisms controlling nocardial pathogenesis. Current data suggest that much of the organism's virulence is due to a variety of substances associated with the bacterial cell envelope. These components are important in: selective organ tropisms of the bactyeria within the host; altering phagocyte function by inhibiting phagosome-lysosome fusion and reducing lysosomal enzyme activity; neutralization of bactericidal oxidative products by phagocytes; toxicity towards host cells; and the ability of the nocardial cell to grow within host cells and function as a faultative intracellular pathogen. Cell wall and cytoplasmic components of N. asteroides will be fractionated by standard biochemical procedures. By utilizing hybridoma technology, monoclonal antibodies will be produced against those specific cellular fractions and then the antibodies will be utilized to purify further the specific antigens. By utilizing in vitro studies with either murine macrophages or human phagocytes and in vivo models in mice, these purified, highly specific antibodies and antigens will permit identification of the components of the cells that are important in each aspect of nocardial pathogenesis. These results will permit recognition of substances that may be utilized for better immunodiagnostic procedures. Further, they will lay a foundation to permit immunoprophylactic and immunotherapeutic augmentation of host resistance in immunocompromised hosts.
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