Abstract
The etiological agent of Chagas disease, Trypanosoma cruzi contains 2-Cys peroxiredoxins (Prx) localized in mitochondria (TcMPX) and cytosol (TcCPX) as part of its antioxidant armamentarium. The participation of these Prx in the defense towards the host and parasite-derived oxidative stress led us to postulate them as virulence factors. In addition to its peroxidase activity, 2-Cys Prx have alternative functions. In this work, we studied the peroxidase, holdase and signaling functions of TcMPX in the context of parasite-macrophage and drug interactions (nifurtimox, NFX). Parasites overexpressing TcMPX were more infective compared to wild type (wt) under macrophage-derived O2•- and/or ONOO- generation indicating the protective role of TcMPX during infection. Additionally, TcMPX overexpressers also contain higher holdase activity and were more resistant to NFX-treatment. Importantly, wt parasites treated with NFX increase TcMPX protein content suggesting the involvement of the holdase activity in the stress response towards NFX. Finally, under stress conditions, TcMPX protein-disulfide adducts were detected indicating additional redox protein partners which may participate in the biological actions of TcMPX.
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