Characterization of Trichomonas vaginalis rhomboid proteases and surface proteins that contribute to host: parasite interactions.

摘要

Trichomonas vaginalis is a flagellated, protozoan parasite that causes trichomoniasis, the most common non-viral sexually transmitted infection in the world. While T. vaginalis infection is usually asymptomatic, long-term effects include associations with adverse pregnancy outcomes, cervical cancer and aggressive prostate cancer, and increased risk of HIV infection. Therefore, the public health threat posed by this parasite is high, yet little is known about its pathogenic mechanisms. As an obligate, extracellular parasite, T. vaginalis needs to attach to epithelial cells in order to gain a foothold in its host and maintain infection. However, only a few specific molecular players that contribute to these interactions have been reported. Given the roles of rhomboid proteases in cell signaling, modification of the cell surface, and contribution to pathogenesis in other protozoan parasites, we were interested in studying whether T. vaginalis also has functionally active rhomboid proteases. In this study, we demonstrate that two T. vaginalis rhomboids are proteolytically active and named them TvROM1 and TvROM3. We also report that TvROM1 has a role in promoting T. vaginalis attachment to host cells and lysis of host cells. Furthermore, we have begun to unravel the mechanism of action for TvROM1 by the identification of two substrates also located at the cell surface. In our desire to discover additional factors that contribute to pathogenesis, we characterized various proteins that had been previously identified in the T. vaginalis cell surface proteome. We found that one protein, called TSP6, plays a sensory role based on striking relocalization of the protein upon contact with host cells, and a role in promoting parasite migration. We also identified another protein, TVAG_393390, which can increase both attachment to host cells and cytolysis of host cells and may function as a cadherin-like protein. Overall, the results from these studies have allowed us to gain insight about the contribution of rhomboid proteases and several surface proteins to host: parasite interactions-opening up a larger window of potential targets for therapeutic intervention to combat this widespread human pathogen.