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Date of Award

2016

Document Type

Thesis - Pacific Access Restricted

Degree Name

Master of Science (M.S.)

Department

Biological Sciences

First Advisor

Lisa Wrischnik

First Committee Member

Kirkwood Land

Second Committee Member

Douglas Weiser

Abstract

The Role of TvTrxR in Drug Resistance and Characterization of TvRad51 in Homologous Recombination in Trichomonas vaginalis Abstract By Melissa Hopper University of the Pacific 2016 In recent years, prevalence of metronidazole-resistant cases of Trichomonas vaginalis has been on the rise. With nearly 10% of strains resistant to metronidazole, new treatments to combat this parasite have become a necessity. FDA-approved drug screens have identified the compound, auranofin, as an effective agent against similar protozoans. The mechanism of inhibition by auranofin has been found to proceed through inhibition of the thioredoxin-based anti-oxidant pathway, targeting the enzyme thioredoxin reductase (TrxR). In this study, auranofin was found to be an effective inhibitor of T. vaginalis TrxR activity. Auranofin was also found to be an effective inhibitor of several trichomonad strains in culture, exhibiting IC50 values comparable to metronidazole. These studies indicate that auranofin is a promising agent for treatment of trichomoniasis. Another aspect of T. vaginalis biology addressed in this study is the ability of T. vaginalis to carry out homologous recombination (HR), a process used to repair double-stranded breaks in DNA. The protein radiation sensitive protein 51 (Rad51) plays a crucial role in the process of HR in mitotic and meiotic recombination. In this study, experiments were carried out to elucidate the role of T. vaginalis Rad51 in homologous recombination. TvRad51 was found to exhibit nuclear localization and was capable of carrying out ATP hydrolysis. Rad51 was shown to be up-regulated at the protein level in T. vaginalis in response to treatment with DNA-damaging agents. In addition, TvRad51 was capable of binding the BRC repeat region of TvBRCA2. These results indicate that T. vaginalis upregulates expression of Rad51 protein in response to certain forms of DNA damage and TvRad51 may be capable of carrying out HR mediated by different binding partners.

Pages

112

ISBN

9781369117264

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