Studies on the Host-Parasite Relationship in Trichomoniasis

Bremner, Alison F (1988) Studies on the Host-Parasite Relationship in Trichomoniasis. PhD thesis, University of Glasgow.

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Abstract

An investigation to elucidate the pathogenic mechanisms of Trichomonas vaginalis, the flagellate protozoan of man responsible for the sexually transmitted disease trichomonal vaginitis was undertaken. The research was undertaken in collaboration with Dr M. J. North and Dr B. C. Lockwood of the University of Stirling. The project involved the use of models of the trichomonad infection including an in vivo the subcutaneous mouse model, an intravaginal mouse model developed as part of this project, an in vitro model of the interaction of T. vaginalis and mammalian cells, again developed for this project. As virulence is believed to attenuate with prolonged cultivation in vitro a collection of fresh isolates was obtained from patients at Glasgow Royal Infirmary genito-urinary clinic. This collection of isolates was then compared for their effect in each of the models: growth kinetics in axenic culture were measured as generation time is thought to correlate with virulence of isolates; the cytotoxicity of isolates towards mammalian cells was measured and compared to growth rate of subcutaneous lesions in mice and infectivity to mice intravaginally. It was found that some correlation did occur between effects in the subcutaneous and intravaginal mouse models and the effect on mammalian cell lines, but no correlation occurred between effect in these models and growth kinetics of isolates in axenic culture. Some biochemical properties of the collection of isolates were also investigated by our co-workers at Stirling University, these included a comparison of ornithine decarboxylase activity and a comparison of proteinase activity in the isolates. Again, no correlation was found between these activities and the effects of isolates in the models used. The models used to compare isolates were used to test the effects of a number of inhibitors. Firstly, the effect of leupeptin, an inhibitor of cysteine proteinase activity, was examined in each of the models. Cysteine proteinases are known to be present in large amounts in T. vaginalis, although their role in the biochemistry of the parasite is unknown. Cysteine proteinases have been implicated in pathogenicity of some other parasitic protozoa e. g. Entamoeba histolytica and for these reasons a potential role of cysteine proteinases in trichomonad pathogenicity was investigated. At concentrations which had only a slight inhibitory effect on growth in axenic culture, leupeptin totally prevented trichomonad cytotoxicity towards mammalian cells in vitro; an effect on the subcutaneous mouse model was observed although leupeptin proved highly toxic to mice. Numerous variations in method were tested to achieve maximum effect of leupeptin e.g. multiple dosing, route, times of administration and pretreatment, however the maximum effect achieved was a delay in growth of subcutaneous lesions, rather than an inhibition of lesion growth. The effect of leupeptin on intravaginal infections in mice was investigated, mice infected intravaginally with T. vaginalis were treated in the same way as achieved maximum effect against the subcutaneous infection, however, no effect on infectivity was observed. These results therefore indicate that cysteine proteinases are involved in pathogenicity of T. vaginalis although they are by no means the only factor and may play a minor role in the host-parasite relationship. This was also indicated by the work carried out at Stirling showing that proteinase activity of the various isolates did not appear to correlate with virulence as measured by any of our models. The same model systems were then used to investigate the effects of difluoromethylornithine (DFMO). This is a specific inhibitor of ornithine decarboxylase, an enzyme involved in the synthesis of polyamines, most commonly putrescine, spermidine and spermine which are known to be required for trichomonad growth although their function has not yet been precisely defined. A link between polyamines and trichomonad infection has been suggested by the presence of putrescine in the vaginal fluid of trichomoniasis patients. DFMO has excited interest as a potential drug against polyamine biosynthesis and so preventing growth of infectious organisms and tumours, and it has been shown to be effective against certain protozoan infections, especially trypanosomiasis. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Zoology, Parasitology
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77709
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53
URI: http://theses.gla.ac.uk/id/eprint/77709

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