Not much is known about the molecular mechanisms which govern the Trypanosoma cruzi-host interaction. Our long term goals are to identify, isolate and characterize biologically active mlecules crucial to the infective process, and test their usefullness in prevention, therapy and diagnosis of Chagas' disease. One such molecule is the neuramindase of T. cruzi whose presence in the parasite was discovered in our laboratory. Because neuraminidases in general are capable of perturbing critical physiological processes of the mammalian host, the parasite enzyme is potentially relevant to the pathogenesis of Chagas' disease. The present proposal will focus on the isolation and determination of molecular parameters and cellular location of the T. cruzi neuraminidase; on ascribing a role to the enzyme in the host parasite interaction by ascertaining its association with intrinsic biological properties of the trypanosome, its mimicking of the alterations of acutely infected animals, its activity during infection of myocardial cells in vitro, and its value in the immunodiagnosis and prevention of Chagas' disease. Isolation and molecular parameters of the neuraminidase of T. rangeli, a non-pathogen transmitted by the insect vectors of T. cruzi, will also be determined for comparative purposes. For these specific goals, preliminary results were obtained which almost certainly assure a successful outcome for most of the proposed experiments. The rationale for this proposal is based on the importance of neuraminidase in myxoviral and certain bacterial infections. Specific assays and methods involving aspects of cell biology and biochemistry for most of the proposed study have already been developed. The experiments will employ protein, carbohydrate and cell biology techniques. In addition to providing insights into basic mechanisms of Chagas' disease, the results of these studies may also serve as a model of other parasitic diseases.
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