The project represents a continued study of the biochemical cytology of Trichomonas vaginalis, a sexually transmitted common parasite of humans that causes vaginitis and urethritis. The major aspects studied are the interaction of T. vaginalis with metronidazole, the only drug available to treat trichomoniasis, the mechanisms of resistance to this drug in T. vaginalis and the anaerobic and aerobic energy metabolism of the organism and its subcellular organization. Metronidazole susceptible and in vivo resistant T. vaginalis strains will be studied. Kinetics of drug cytotoxicity (Kill-curves) will be established under anaerobic and aerobic conditions and in the presence of reducing agents and radical scavangers for nitroimidazoles of different electron affinity to explore the details of the interaction and define the in vitro conditions necessary for the expression of drug resistance. Carbon balances and adenylate charge of T. vaginalis under different conditions will be determined to elucidate the metabolic adaptations of the organism. Enzymatic studies will explore the phenomenon of 0(2) toxicity and the mechanisms available to T. vaginalis for protection against this toxicity. Analysis of the biochemistry of hydrogenosomes, unique redox organelles of T. vaginalis, will be done with EPR spectroscopy to define the unusual electron transport system of the organelle and to study the interaction of this system with antitrichomonad drugs. The aerobic and anaerobic metabolism of isolated hydrogenosomes will be explored to elucidate the functional role of the organelle in T. vaginalis. The results will contribute to our understanding of the adaption of T. vaginalis, an anaerobic organism, to its natural environment. They also will contribute to our understanding of the mode of actiuon of antitrichomonad nitroimidazoles and especially of the recently recognized drug resistance in T. vaginalis.
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