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Infection by Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, depends on reactive oxygen species (ROS), which has been described to induce parasite proliferation in mammalian host cells. It is unknown how the parasite manages to increase host ROS levels. Here, we found that intracellular T. cruzi forms release in the host cytosol its major cyclophilin of 19 kDa (TcCyp19). Parasites depleted of TcCyp19 by using CRISPR/Cas9 gene replacement proliferate inefficiently and fail to increase ROS, compared to wild type parasites or parasites with restored TcCyp19 gene expression. Expression of TcCyp19 in L6 rat myoblast increased ROS levels and restored the proliferation of TcCyp19 depleted parasites. These events could also be inhibited by cyclosporin A, (a cyclophilin inhibitor), and by polyethylene glycol‐linked to antioxidant enzymes. TcCyp19 was found more concentrated in the membrane leading edges of the host cells in regions that also accumulate phosphorylated p47phox, as observed to the endogenous cyclophilin A, suggesting some mechanisms involved with the translocation process of the regulatory subunit p47phox in the activation of the NADPH oxidase enzymatic complex. We concluded that cyclophilin released in the host cell cytosol by T. cruzi mediates the increase of ROS, required to boost parasite proliferation in mammalian hosts. [ABSTRACT FROM AUTHOR]

Trypanosomatids are parasites of worldwide distribution with relevant importance in human and veterinary health, which inhabit invertebrate and vertebrate hosts, such that they are exposed to large environmental variations during their life cycle. The signalling mechanisms and molecular basis that lead these parasites to adjust to such distinct conditions are beginning to be understood, and are somehow related to modifications in gene expression. Although the control of gene expression in this group of organisms happens predominantly at the post-transcriptional level, they present modifications in chromatin that has been implicated in transcription initiation, replication and DNA repair. Here, we explore the current scenario of chromatin alterations in these protozoans and how these changes affect transcription, replication and DNA repair in response to environmental modifications. [ABSTRACT FROM AUTHOR]