Opportunistic pathogens in immunocompromised individuals represent a major and expanding public health problem. Nocardia asteroides is an important """"""""opportunistic pathogen"""""""" that frequently causes serious pulmonary and systemic disease in AIDS patients as well as a large variety of immunocompromising conditions. Also, these organisms cause life threatening infections (especially in the brain) in otherwise healthy persons. Recently, it was shown that Nocardia causes parkinson's-like disease in experimental animals which suggest a possible role for Nocardia in Parkinson's disease. Furthermore, a variety of other neurological signs are recognized in subclinically infected mice, suggesting a possible involvement of Nocardia in several types of neurodegenerative diseases. The mechanisms controlling nocardial pathogenesis are not understood. Studies show that most of the virulence of H. asteroides results from substances secreted into the environment or associated with the cell envelope. These compounds are important in: adherence and selective growth of the bacteria in the host; altering phagocyte function by inhibiting phagosome-lysosome fusion; blocking phagosomal acidification; altering lysosomal enzyme activity; neutralization of microbicidal activities of phagocytes; toxicity toward host cells; and the ability of Nocardia to grow in cells. The goals of this proposal are to: 1) elucidate the relationship of the structure of glycolipids to pathogenesis, especially in the brain; and 2) determine the mechanisms of nocardial interactions within specific regions of the brain. To achieve these goals, glycolipids will be purified by standard biochemical procedures combined with an HPLC-MS. Defined components will be incorporated into liposome carriers and their ability to modulate host cell activities will be quantitated. N. asteroides GUH-2 as well as specific mutants will be used, and their interactions within specific regions of the brain will be studied by EM, and by histochemical, cytochemical, immunologic and biochemical methodologies. This approach focused on interactions within the brain should define the specific roles of nocardial glycolipids in nocardial pathogenesis and lead to a better understanding of the complex interactions of nocardia within the brain that results in different neurodegenerative responses. A complete understanding of these interactions are essential and should result in better methods of diagnosis, treatment, management and prevention of life threatening diseases caused by Nocardia.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Bacteriology and Mycology Subcommittee 2 (BM)
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University of California Davis
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United States
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Beaman, Blaine L; Tam, Stanley (2008) An unusual murine behavior following infection with log-phase Nocardia asteroides type 6 strain GUH-2 (Nocardia cyriacigeorgica GUH-2). Microbes Infect 10:840-3
Hyland, K; Beaman, B L; LeWitt, P A et al. (2000) Monoamine changes in the brain of BALB/c mice following sub-lethal infection with Nocardia asteroides (GUH-2). Neurochem Res 25:443-8
Beaman, B L; Canfield, D; Anderson, J et al. (2000) Site-specific invasion of the basal ganglia by Nocardia asteroides GUH-2. Med Microbiol Immunol 188:161-8
Beaman, B L; Beaman, L (1998) Filament tip-associated antigens involved in adherence to and invasion of murine pulmonary epithelial cells in vivo and HeLa cells in vitro by Nocardia asteroides. Infect Immun 66:4676-89
Friedman, C S; Beaman, B L; Chun, J et al. (1998) Nocardia crassostreae sp. nov., the causal agent of nocardiosis in Pacific oysters. Int J Syst Bacteriol 48 Pt 1:237-46
Ioneda, T; Beaman, B L (1996) Thermospray mass spectral analyses of corynomycolic acids and their derivatives. Chem Phys Lipids 83:123-30
Beaman, B L (1996) Differential binding of Nocardia asteroides in the murine lung and brain suggests multiple ligands on the nocardial surface. Infect Immun 64:4859-62
Alcendor, D J; Chapman, G D; Beaman, B L (1995) Isolation, sequencing and expression of the superoxide dismutase-encoding gene (sod) of Nocardia asteroides strain GUH-2. Gene 164:143-7
Beaman, L; Beaman, B L (1994) Differences in the interactions of Nocardia asteroides with macrophage, endothelial, and astrocytoma cell lines. Infect Immun 62:1787-98
Beaman, B L; Beaman, L (1994) Nocardia species: host-parasite relationships. Clin Microbiol Rev 7:213-64

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