Characterisation of unusual DNA glycosylases from Trichomonas vaginalis

Hayes, Amber and Allinson, Sarah (2019) Characterisation of unusual DNA glycosylases from Trichomonas vaginalis. Masters thesis, Lancaster University.

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Abstract

Trichomonas vaginalis is a parasitic protozoan responsible for 170 million new infections each year and is the most prevalent non-viral sexually transmitted infection worldwide according to The World Health Organisation. Research on the parasites pathogenicity and lifestyle has been limited until the publishing of the parasites’ genome in 2007 and an emergence of studies documenting links between T. vaginalis infection and a number of adverse health outcomes, including an increased risk of HIV acquisition and cervical cancer. Research into DNA repair pathways within this organism have also been limited. In this research I describe two DNA 3-methyl adenine glycosylase homologues (TvAAG1 and TvAAG2) characterised via biochemical methods. In addition to the creation of an atlas of DNA repair proteins and enzymes present in T. vaginalis, and a close evolutionary relative, Tritrichomonas foetus via bioinformatical analysis. Biochemical analysis of TvAAG1 reveals it as the first bifunctional AAG type enzyme to be described. Bioinformatic analysis suggests TvAAG1 and TvAAG2 are most likely the result of horizontal gene transfer between an ancestor of both T. vaginalis and T. foetus and a donor belonging to the Bacteroidetes phylum. The DNA repair pathways of both parasites are reduced compared to humans. The parasites have the main components for base excision repair, mismatch repair and homologous recombination repair but not non-homologous end joining. In light of reports of antibiotic resistance further research should be done on the parasites DNA repair pathway to identify potential novel drug targets for treatment of T. vaginalis infection.