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.
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