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Dependence of Trichomonas vaginalis upon polyamine backconversion
Nigel Yarlett1, Martha P Martinez1, Burt Goldberg2,1
1Haskins Laboratories1 and Department of Chemistry and Physical Sciences2, Pace University, 41 Park Row, New York, NY 10038, USA.
Microbiology (Reading, England)
|October 6, 2000
Summary
Trichomonas vaginalis converts spermine to spermidine via detected enzyme activities, lacking forward polyamine synthesis. Bis(alkyl) polyamine analogues show potential as antitrichomonad agents by reducing polyamine levels.
Area of Science:
- Biochemistry
- Parasitology
- Molecular Biology
Background:
- Trichomonas vaginalis lacks a forward-directed polyamine synthetic pathway.
- Polyamines are essential for parasite growth and survival.
- Understanding polyamine metabolism is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the metabolic fate of spermine and putrescine in T. vaginalis.
- To identify and characterize key enzymes involved in polyamine interconversion.
- To evaluate the potential of polyamine analogues as antitrichomonad agents.
Main Methods:
- Radiolabeling of spermine and putrescine to trace metabolic pathways.
- Enzyme assays to detect and quantify spermidine:spermine N(1)-acetyltransferase (SSAT) and polyamine oxidase activity.
- Subcellular fractionation to localize enzyme activity.
- Growth inhibition studies using bis(alkyl) polyamine analogues.
Main Results:
- T. vaginalis forms spermidine from spermine but does not metabolize exogenous putrescine.
- SSAT and polyamine oxidase activities were detected, converting spermine to spermidine.
- SSAT is primarily cytosolic, while polyamine oxidase is in the hydrogenosome-enriched fraction.
- Di(ethyl)norspermine significantly reduced intracellular spermidine and spermine concentrations, impacting parasite growth.
Conclusions:
- T. vaginalis utilizes salvage pathways for polyamine metabolism, converting spermine to spermidine.
- The identified enzymes SSAT and polyamine oxidase are potential targets for antitrichomonad drug development.
- Bis(alkyl) polyamine analogues demonstrate significant potential as therapeutic agents against T. vaginalis infections.