Legionella micdadel is the etiological agent of an acute pneumonia which occurs primarily among immunosuppressed patients, particularly organ transplant recipients. This project will examine several aspects of the virulence of, immunity to, and antimicrobial susceptibility of this organism. L. micdadei, an intracellular pathogen, appears to escape the normal bactericidal defense mechanisms provided by phagocytic cells such polymorphonuclear leukocytes, alveolar macrophages and blood monocytes. In vitro studies of the interaction between the organism and the above phagocytic cells will be performed in an effort to determine if components or properties of the bacterial cell are responsible for the depression of the antibacterial mechanisms of the phagocytic cells. In particular, the role of a recently discovered cytotoxin in the depression of phagocytic killing will be examined. A guinea pig model of immunity following pulmonary infection with L. micdadei has been developed and will be used to study the interaction between the organism and the humoral and cellular components of the immune system in an effort to identify which elements are protective for the immune animal. It has already been determined that alveolar macrophages from immune animals do not alone inhibit the growth of the organism. The contribution of other cellular components of the immune system, namely lymphocytes, to the killing of L. micdadei by phagocytic cells will be measured in vitro and in vivo. Finally, the effect of the intracellular location on the antimicrobial susceptibility of L. micdadei will be studied. The intracellular concentration of antimicrobials which are known to be therapeutically effective against the bacterium will be compared to those of agents which are known to be ineffective.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI017047-04A2
Application #
3126962
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1980-08-01
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Dowling, J N; Saha, A K; Glew, R H (1992) Virulence factors of the family Legionellaceae. Microbiol Rev 56:32-60
Saha, A K; Mukhopadhyay, N K; Dowling, J N et al. (1990) Characterization of a phosphomonoesterase from Brucella abortus. Infect Immun 58:1153-8
Holtmann, H; Shemer-Avni, Y; Wessel, K et al. (1990) Inhibition of growth of Chlamydia trachomatis by tumor necrosis factor is accompanied by increased prostaglandin synthesis. Infect Immun 58:3168-72
Pasculle, A W; Veto, G E; Krystofiak, S et al. (1989) Laboratory and clinical evaluation of a commercial DNA probe for the detection of Legionella spp. J Clin Microbiol 27:2350-8
Saha, A K; Dowling, J N; Mukhopadhyay, N K et al. (1989) Legionella micdadei protein kinase catalyzes phosphorylation of tubulin and phosphatidylinositol. J Bacteriol 171:5103-10
Saha, A K; Dowling, J N; Mukhopadhyay, N K et al. (1988) Demonstration of two protein kinases in extracts of Legionella micdadei. J Gen Microbiol 134:1275-81
Saha, A K; Dowling, J N; Pasculle, A W et al. (1988) Legionella micdadei phosphatase catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate in human neutrophils. Arch Biochem Biophys 265:94-104
Levi, M H; Pasculle, A W; Dowling, J N (1987) Role of the alveolar macrophage in host defense and immunity to Legionella micdadei pneumonia in the guinea pig. Microb Pathog 2:269-82
Das, S; Saha, A K; Remaley, A T et al. (1986) Hydrolysis of phosphoproteins and inositol phosphates by cell surface phosphatase of Leishmania donovani. Mol Biochem Parasitol 20:143-53
Dowling, J N; McDevitt, D A; Pasculle, A W (1985) Isolation and preliminary characterization of erythromycin-resistant variants of Legionella micdadei and Legionella pneumophila. Antimicrob Agents Chemother 27:272-4

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