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Polyamine biosynthesis in trichomonads.

M J North, B C Lockwood, A F Bremner

    Molecular and Biochemical Parasitology
    |June 1, 1986
    PubMed
    Summary
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    Trichomonad parasites like Trichomonas vaginalis accumulate polyamines from their environment. This uptake mechanism explains why drugs targeting polyamine synthesis, such as alpha-difluoromethylornithine (DFMO), are ineffective in lab cultures but may work in vivo.

    Area of Science:

    • Biochemistry
    • Parasitology
    • Molecular Biology

    Background:

    • Trichomonad parasites, including Trichomonas vaginalis, Tritrichomonas foetus, and Trichomitus batrachorum, exhibit distinct polyamine profiles.
    • These protozoa possess varying levels of ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis.

    Purpose of the Study:

    • To investigate the polyamine content and decarboxylase activities in three trichomonad species.
    • To assess the impact of alpha-difluoromethylornithine (DFMO), an ODC inhibitor, on trichomonad polyamine metabolism and growth.
    • To determine the role of exogenous polyamine uptake in the in vitro efficacy of DFMO.

    Main Methods:

    • Quantification of putrescine, spermidine, and spermine concentrations in cultured trichomonads.
    • Assay of ornithine decarboxylase (ODC) and S-adenosyl-methionine decarboxylase activities.

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  • Growth inhibition and polyamine uptake studies using DFMO in axenic cultures of Trichomonas vaginalis.

    • Main Results:

    • All three species showed high putrescine and lower spermidine/spermine levels, with significant differences in ODC activity (T. vaginalis > T. batrachorum).
    • DFMO severely inhibited T. vaginalis ODC but had minimal impact on parasite growth in vitro, suggesting an alternative polyamine acquisition strategy.
    • DFMO-treated T. vaginalis cells demonstrated enhanced uptake of exogenous putrescine, indicating reliance on environmental polyamine sources.

    Conclusions:

    • Trichomonad parasites can effectively scavenge polyamines from their growth medium.
    • The ability to accumulate exogenous polyamines explains the limited in vitro efficacy of ODC inhibitors like DFMO.
    • In vivo efficacy of DFMO may differ from in vitro results due to the absence of readily available exogenous polyamine sources.