The roles and regulation of autophagy on the survival of Trichomonas vaginalis under glucose restriction

Autophagy, a highly conserved self-digesting mechanism, is used by eukaryotic cells to degrade their proteins and organelles in response to starvation. Previous studies have demonstrated the critical roles of autophagy in cell survival, stress resistance, and lifespan extension in many model organisms. However, in contrast to yeast and higher eukaryotes, the significance and the regulation of autophagy in parasitic protozoa is far less understood. Recent studies indicate that autophagy is essential for some parasites to maintain or establish infection. The ultimate goal of this three years research proposal is to elucidate the role of autophagy in T. vaginalis under glucose restriction (GR). Bioinformatics analyses of the T. vaginalis genome revealed that this parasite possesses a putative Atg8 conjugation system but lacks an Atg5-to-Atg12 conjugation system, suggesting that T. vaginalis utilizes a different autophagy pathway from yeast and mammals. Our pilot experiments revealed that T. vaginalis survives longer in GR medium compared with the cells grown in glucose-rich medium. In addition, the presence of autophagy in cells under GR has been shown by autophagy-specific staining. Moreover, the expression of the universal autophagy regulator sir2 gene expression was up-regulated under GR. Our preliminary data provided solid evidence that T. vaginalis contains a unique autophagy system which may play important roles in cell survival and establishment of infections. Based on the findings in the past and new perspectives on autophagy, we propose to study autophagy in the protozoan parasite T. vaginalis with the following specific aims: 1. To verify the existence of autophagy in T. vaginalis 2. To study the regulation of GR-induced autophagy in T. vaginalis. 3. To elucidate the role of GR-induced autophagy in the cell survival of T. vaginalis The results of this study will not only elucidate the roles and regulation of autophagy in T. vaginalis, but also pave a way to study the evolution of autophagy in different organisms. In addition, the differences in the autophagy pathway between T. vaginalis and their hosts may provide additional targets for the development of new therapeutics against trichomonaisis.

Project ID:PC10202-0579
External Project ID:NSC101-2320-B182-025-MY3