The TcVps34-TcVps15 complex regulates parasite metacyclogenesis and host cell infection in Trypanosoma cruzi.

The processes of autophagy and metacyclogenesis are essential for the survival and progression of the cell cycle of Trypanosoma cruzi, the etiological agent of Chagas disease. There is experimental evidence of an interconnection between both pathways in this parasite. Previously, it has been shown that the phosphatidylinositol 3-kinase TcVps34 and its regulatory protein kinase, TcVps15, are essential for autophagy in T. cruzi. In this work, we studied the role of these two proteins in metacyclogenesis and infection. Here, we demonstrate that both proteins are involved in the differentiation process. In addition, the alternative overexpression of either TcVps15 or TcVps34 increases the autophagic process after the first two hours of induction of metacyclogenesis and increases the activity of degradative compartments. Finally, both overexpressing cell lines show reduced infection levels in Vero host cells; additionally, these parasites display a downregulation of the surface glycoprotein gp82-associated with promoting the host infection-and a mild upregulation of gp90, known to negatively modulate infectivity. In conclusion, this study highlights the critical roles of the TcVps34-Vps15 complex in regulating the interplay between autophagy and metacyclogenesis in Trypanosoma cruzi, suggesting a contribution of both proteins to a successful infection establishment.