Date of Award

1992

Degree Name

M.S. in Biology

Abstract

Morphological and biochemical transformation of bloodstream form trypanosomes from long slender (LS) to short stumpy (SS) forms is an important event for completion of the trypanosome life cycle because it pre-adapts the trypanosome for the change of environment upon transfer to the tsetse fly vector. The drug a-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, inhibits polyamine biosynthesis and has been found to induce the transformation from LS to SS forms. DFMO has been used routinely as an inducer of LS to SS transformation in molecular and biochemical experiments studying this transformation event. In this study we have compared natural and DFMO-induced transformation to see if DFMO is in fact a good model of trypanosomal transformation. A pleomorphic and a monomorphic strain of T. brucei brucei induced with DFMO were compared with respect to growth characteristics, morphology, intracellular polyamine levels, intracellular ATP levels, protein synthesis, and two-dimensional gel electrophoresis of whole cell iiilysates labeled with “S-methionine. The results show that both DFMO-induced and natural transformation exhibit decreased protein synthesis, increased intracellular ATP, and a generalized decrease in the number of biosynthetically labeled proteins on two-dimensional gels. The levels of the polyamines putrescine and spermidine are greatly decreased in DFMO-induced trypanosomes, however, in naturally transforming trypanosomes putrescine is slightly increased and spermidine is increased 1.6 times that of LS trypanosomes. We therefore conclude that the natural transformation of bloodstream form trypanosomes does not involve a decrease in the intracellular polyamine pools, as is associated with DFMO-induced transformation. Therefore other mechanism(s) may be involved in regulating the natural transformation process.

Keywords

Trypanosoma brucei, Ornithine decarboxylase, Biochemical toxicology

Comments

Illustrative matter includes some mounted photographs

Rights Statement

Copyright © 1992, author

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