UCLA

Trichomonas vaginalis is a unicellular extracellular sexually transmitted parasite. While the infection may be cleared by nitroimidazole drugs, in cases where re-infection occurs or the treatment fails, the infected individual may live with inflammation, soreness, pain or itch surrounding urogenital areas without an alternative solution. To establish an infection, T. vaginalis attaches to the host and acquires nutrients from the host. Several parasite surface molecules and its secreted exosomes have been shown to be important for the parasite attachment to the host. However, none of the factors identified is solely responsible for host cell binding. In this study, we characterize a parasite surface protein TVAG_393390 (or cadherin-like protein) that significantly increases host binding and killing when it is overexpressed. In addition, to also understand how the parasite survives in the host under nutrient-deficient conditions, we unravel the role of a survival protein in the parasite (TvMIF) that is homologous to human macrophage migration inhibitory factor (huMIF). We found that TvMIF-overexpressing parasites gain a strong survival advantage under nutrient stress. To obtain further insights into functions of parasite proteins, we adapted gene knockout method CRISPR (cluster regularly interspaced palindromic repeat)-Cas9 (CRISPR-associated protein 9) in T. vaginalis to efficiently knock out genes of interest. We then successfully knocked out TvMIF gene using CRISPR-Cas9 and observed a significant reduction in the survival of TvMIF knockout cells compared to the wild-type when these parasites were serum-starved. Last, we examine the human innate immune responses to T. vaginalis encounter. Human macrophages and dendritic cells produce strong inflammatory responses when T. vaginalis and Mycoplasma hominis are both present but remarkably less when M. hominis is absent. Together, these data reveal several independent mechanisms which allow T. vaginalis to successfully establish infection in human bodies and provide a framework for future studies on the “trichy” parasite.