Drug Resistance Mechanisms of Trichomonas vaginalis

Authors

• Keonte Graves, University of Alabama at Birmingham

Advisor(s)

William Geisler

Committee Member(s)

Christina Muzny
Jan Novak
Stephen Watts
W Secor

School

College of Arts and Sciences

Document Type

Dissertation

Department (new version)

Biology

Date of Award

9-9-2024

Abstract

Trichomonas vaginalis is a facultative anaerobic parasitic protozoan and the main causative agent of the most common non-viral sexually transmitted infection, trichomoniasis. Trichomoniasis affects both men and women but is more commonly observed in women. The majority of infections are asymptomatic, but those with symptomatic infections often experience malodorous and discolored vaginal discharge, pruritis, dysuria, and/or dyspareunia. T. vaginalis infections have been associated with multiple adverse health outcomes including an increased risk of acquiring HIV and other STIs, infertility, adverse birth outcomes, and cervical cancer. The only current FDA-approved treatments come from the 5-nitroimidazole class of drugs (metronidazole, tinidazole, and secnidazole). Surprisingly, resistance was observed as early as a few years after the introduction of metronidazole as a treatment option for trichomoniasis in the early 1960s. The prevalence of resistance has been estimated to be between 4-10%. However, the true prevalence of resistance remains unknown due to the lack of surveillance data. The focus of my Ph.D. dissertation research was to characterize the mechanisms of resistance in T. vaginalis and identify potential novel gene targets that could serve as focal points in the development of alternative treatment options outside of the 5-nitroimidazole drug class. Additionally, I aimed to establish the break-point for susceptibility of the next-generation 5-nitroimidazole, secnidazole, which was recently FDA-approved for use in the treatment of T. vaginalis infections. Moreover, I performed drug susceptibility assays on metronidazole-resistant and susceptible T. vaginalis isolates to investigate the in vitro activity of two antiprotozoal agents outside of the 5-nitroimidazole drug class, nitazoxanide and its metabolite tizoxanide.

ProQuest ID

https://proquest.com/docview/3101853442