Abstract
Trypanosoma cruzi is the etiological agent of Chagas disease. It affects eight million people worldwide and can be spread by several routes, such as vectorborne transmission in endemic areas and congenitally, and is also important in non-endemic regions such as the United States and Europe due to migration from Latin America. Cyclophilins (CyPs) are proteins with enzymatic peptidyl-prolyl isomerase activity (PPIase), essential for protein folding in vivo. Cyclosporin A (CsA) has a high binding affinity for CyPs and inhibits their PPIase activity. CsA has proved to be a parasiticidal drug on some protozoa, including T. cruzi. In this review, we describe the T. cruzi cyclophilin gene family, that comprises 15 paralogues. Among the proteins isolated by CsA-affinity chromatography, we found orthologues of mammalian CyPs. TcCyP19, as the human CyPA, is secreted to the extracellular environment by all parasite stages and could be part of a complex interplay involving the parasite and the host cell. TcCyP22, an orthologue of mitochondrial CyPD, is involved in the regulation of parasite cell death. Our findings on T. cruzi cyclophilins will allow further characterization of these processes, leading to new insights into the biology, the evolution of metabolic pathways, and novel targets for anti-T. cruzi control.
Highlights
Introduction to Trypanosoma cruzi Infection andChagas DiseaseTrypanosoma cruzi is an hemoflagellate parasitic protozoon and the etiological agent of Chagas disease
Trypanosoma cruzi, as most of the organisms studied to date, has a family of ubiquitous and highly conserved proteins named cyclophilins that mediate protein folding events, catalizing the interconversion of the cis and trans isomers of peptidyl-prolyl bonds in peptides and proteins (peptidyl-prolyl cis-trans isomerase (PPIase) activity) [12], an enzymatic activity inhibited by the immunosuppressive undecapeptide Cyclosporin A (CsA) [13]
Based on our previous results on oxidative stress damage, we investigated whether this cell death mechanism through mPTP opening may occur in T. cruzi
Summary
Trypanosoma cruzi is an hemoflagellate parasitic protozoon and the etiological agent of Chagas disease. There are 30,000 new reported cases of Chagas each year in the Americas and 14,000 people die as a result of the disease, while more than 70 million people live in areas where there is high-risk of transmission [1] This Kinetoplastid unicellular parasite circulates between mammalian hosts and insect vectors, which include a variety of species of Reduviidae (blood-sucking insects known as kissing bugs), widely distributed from Southern. Trypanosoma cruzi, as most of the organisms studied to date, has a family of ubiquitous and highly conserved proteins named cyclophilins that mediate protein folding events, catalizing the interconversion of the cis and trans isomers of peptidyl-prolyl bonds in peptides and proteins (peptidyl-prolyl cis-trans isomerase (PPIase) activity) [12], an enzymatic activity inhibited by the immunosuppressive undecapeptide Cyclosporin A (CsA) [13]. The T. cruzi cyclophilin of 19 kDa, TcCyP19, has a 72% protein sequence identity with the human.
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