Pneumocystis carinii (PC) is an opportunistic pathogen that causes lethal pneumonia in immune compromised patients. In recent years the incidence of PC infections has increased dramatically, due to the increasing number of patients with the Acquired Immune Deficiency Syndrome (AIDS). Pneumocystis pneumonia is the leading cause of morbidity and mortality of AIDs patients, and it clearly constitutes a major medical problem. The usual problems of epidemiology, diagnosis, and treatment of Pneumocystis pneumonia are made more difficult because little is known about the basic biology of PC. The overall goals for this project are (a) to thoroughly describe the ultrastructure of the trophic forms and the cyst stages of Pneumocystis carinii (PC), (b) to compare rat and human PC, and (c) to determine the PC life cycle in vivo and in vitro.
The specific aims are as follows: (1) study the ultrastructure of PC by 8 different fixation modes and transmission electron microscopy (EM) of thin sections; (a) in vivo, by studying PC in intact rat lung, (b) in vivo, by studying PC in rat lung homogenates, (c) in vivo, by studying human PC in bronchoalveolar lavage samples, and (d) in vitro, by studying PC in primary cultures; (2) characterize the PC life cycle stages in vivo using the rat as an animal model of Pneumocystis pneumonia; (a) in situ in the intact lung, and in lung homogenates, (b) during moderate infection (5-6 weeks), (c) during heavy infection (8-9 weeks), and (d) correlate EM data with light microscopic data from fresh preparations of living PC, stained preparations, and plastic sections; (3) characterize the PC life cycle stages in human bronchoalveolar lavage samples from patients with Pneumocystis pneumonia, and correlate the findings with those from the rat; (4) characterize the life cycle stages in vitro in primary cultures of rat PC; (a) at 12 hours after inoculation (during rapid growth of PC), (b) at 1, 3, 6, and 9 days of culture, (c) correlate the findings with quantitative data on growth kinetics, and (d) correlate life cycle stages with those observed in vivo.
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