Characterization of a Trichomonas vaginalis surface protein that mediates host cell binding and establishment of a mouse model for in vivo study of parasite pathogenesis
- Author(s): Molgora, Brenda
- Advisor(s): Johnson, Patricia J
- et al.
Trichomonas vaginalis is an extracellular, flagellated protozoan parasite and the etiologic agent of trichomoniasis – the most common non-viral sexually transmitted infection worldwide. While the majority of cases are asymptomatic, some individuals exhibit mild symptoms such as inflammation and discharge. Persistent infections can result in more severe outcomes such as infertility, increased risk of HIV infection, and cancer of the cervix or prostate. To establish and maintain an infection, T. vaginalis adheres to the epithelial cells of the urogenital tract and acquires nutrients from the host. Several parasite surface factors as well as secreted exosomes have been shown to play a role in parasite adherence to the host, but no single factor is fully responsible for host cell binding. In this study, we identify a number of differentially expressed putative surface proteins in isogenic parasites which differ in adherence and characterize a T. vaginalis surface protein TVAG_157210 (TvAD1) which mediates parasite binding to host cells via an interaction with host glycosaminoglycans. In addition, we established a male mouse model which introduces the parasites to the prostate using transurethral catheterization. We found that parasites can be successfully introduced into the mouse prostate using this approach and that parasites which are more adherent or are free of their bacterial endosymbiont, Mycoplasma hominis, survive significantly longer than their respective counterparts. Lastly, we adapted the gene editing technology CRISPR (cluster regularly interspaced palindromic repeat)-Cas9 (CRISPR-associated protein 9) for use in T. vaginalis to knockout genes more efficiently. As a result, we were able to knockout TvAD1 in more adherent parasites and observed a significant reduction in parasite adherence to host cells compared to the wild-type more adherent parasites. Overall, these studies have allowed us to gain insight into parasite factors such as surface adherence proteins and its naturally occurring endosymbiont and their role in in vitro and/or in vivo T. vaginalis pathogenesis – opening a window of potential therapeutic targets and methods by which to study their efficacy.