Paracrine Signaling Mediated by the Cytosolic Tryparedoxin Peroxidase of .

Peroxiredoxins are abundant and ubiquitous proteins that participate in different cellular functions, such as oxidant detoxification, protein folding, and intracellular signaling. Under different cellular conditions, peroxiredoxins can be secreted by different parasites, promoting the induction of immune responses in hosts. In this work, we demonstrated that the cytosolic tryparedoxin peroxidase of (cTXNPx) is secreted by epimastigotes and trypomastigotes associated with extracellular vesicles and also as a vesicle-free protein.

Overoxidation and Oligomerization of Cytosolic and Mitochondrial Peroxiredoxins.

Peroxiredoxins (Prxs) have been shown to be important enzymes for trypanosomatids, counteracting oxidative stress and promoting cell infection and intracellular survival. In this work, we investigate the in vitro sensitivity to overoxidation and the overoxidation dynamics of Prxs in parasites in culture and in the infection context. We showed that recombinant m-TXNPx, in contrast to what was observed for c-TXNPx, exists as low molecular mass forms in the overoxidized state.

Genome-wide chromatin interaction map for Trypanosoma cruzi.

Trypanosomes are eukaryotic, unicellular parasites, such as Trypanosoma brucei, which causes sleeping sickness, and Trypanosoma cruzi, which causes Chagas disease. Genomes of these parasites comprise core regions and species-specific disruptive regions that encode multigene families of surface glycoproteins. Few transcriptional regulators have been identified in these parasites, and the role of spatial organization of the genome in gene expression is unclear.

Redox sensitive human mitochondrial aconitase and its interaction with frataxin: In vitro and in silico studies confirm that it takes two to tango.

Mitochondrial aconitase (ACO2) has been postulated as a redox sensor in the tricarboxylic acid cycle. Its high sensitivity towards reactive oxygen and nitrogen species is due to its particularly labile [4Fe-4S] prosthetic group which yields an inactive [3Fe-4S] cluster upon oxidation. Moreover, ACO2 was found as a main oxidant target during aging and in pathologies where mitochondrial dysfunction is implied.

New Insights into the Role of the Aldo-Keto Reductase AKR.

Chagas disease is a zoonotic infectious disease caused by the protozoan parasite . It is distributed worldwide, affecting around 7 million people; there is no effective treatment, and it constitutes a leading cause of disability and premature death in the Americas. Only two drugs are currently approved for the treatment, Benznidazole and Nifurtimox, and both have to be activated by reducing the nitro-group.

De novo sequencing and construction of a unique antibody for the recognition of alternative conformations of cytochrome in cells.

Cytochrome (cyt ) can undergo reversible conformational changes under biologically relevant conditions. Revealing these alternative cyt conformers at the cell and tissue level is challenging. A monoclonal antibody (mAb) identifying a key conformational change in cyt was previously reported, but the hybridoma was rendered nonviable.

The cytosolic tryparedoxin peroxidase from Trypanosoma cruzi induces a pro-inflammatory Th1 immune response in a peroxidatic cysteine-dependent manner.

Trypanosoma cruzi cytosolic tryparedoxin peroxidase (c-TXNPx) is a 2-Cys peroxiredoxin (Prx) with an important role in detoxifying host cell oxidative molecules during parasite infection. c-TXNPx is a virulence factor, as its overexpression enhances parasite infectivity and resistance to exogenous oxidation. As Prxs from other organisms possess immunomodulatory properties, we studied the effects of c-TXNPx in the immune response and analysed whether the presence of the peroxidatic cysteine is necessary to mediate these properties.

Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi.

Although the genome of Trypanosoma cruzi, the causative agent of Chagas disease, was first made available in 2005, with additional strains reported later, the intrinsic genome complexity of this parasite (the abundance of repetitive sequences and genes organized in tandem) has traditionally hindered high-quality genome assembly and annotation. This also limits diverse types of analyses that require high degrees of precision. Long reads generated by third-generation sequencing technologies are particularly suitable to address the challenges associated with T.

Old Yellow Enzyme from Exhibits Prostaglandin Fα Synthase Activity and Has a Key Role in Parasite Infection and Drug Susceptibility.

The discovery that trypanosomatids, unicellular organisms of the order Kinetoplastida, are capable of synthesizing prostaglandins raised questions about the role of these molecules during parasitic infections. Multiple studies indicate that prostaglandins could be related to the infection processes and pathogenesis in trypanosomatids. This work aimed to unveil the role of the prostaglandin Fα synthase OYE in the establishment of infection, the causative agent of Chagas disease.

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition in .

American trypanosomiasis is a chronic and endemic disease which affects millions of people. , its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation.

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers.

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasite-derived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso-N-methylurea (NMU).

Redox metabolism in Trypanosoma cruzi. Biochemical characterization of dithiol glutaredoxin dependent cellular pathways.

In Trypanosoma cruzi, the modification of thiols by glutathionylation-deglutathionylation and its potential relation to protective, regulatory or signaling functions have been scarcely explored. Herein we characterize a dithiolic glutaredoxin (TcrGrx), a redox protein with deglutathionylating activity, having potential functionality to control intracellular homeostasis of protein and non-protein thiols. The catalytic mechanism followed by TcrGrx was found dependent on thiol concentration.

Early Trypanosoma cruzi infection reprograms human epithelial cells.

Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T.

GALNT11 as a new molecular marker in chronic lymphocytic leukemia.

Aberrant mucin O-glycosylation often occurs in different cancers and is characterized by immature expression of simple mucin-type carbohydrates. At present, there are some controversial reports about the Tn antigen (GalNAcα-O-Ser/Thr) expression and there is a great lack of information about the [UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts)] expression in chronic lymphocytic leukemia (CLL). To gain insight in these issues we evaluated the Tn antigen expression in CLL patient samples using two Tn binding proteins with different fine specificity.

Redox metabolism in Trypanosoma cruzi: functional characterization of tryparedoxins revisited.

Tryparedoxins (TXNs) are multipurpose oxidoreductases from trypanosomatids that transfer reducing equivalents from trypanothione to various thiol proteins. In Trypanosoma cruzi, two genes coding for TXN-like proteins have been identified: TXNI, previously characterized as a cytoplasmic protein, and TXNII, a putative tail-anchored membrane protein. In this work, we performed a comparative functional characterization of T.

Cloning, localization and differential expression of the Trypanosoma cruzi TcOGNT-2 glycosyl transferase.

The surface of Trypanosoma cruzi is covered by a dense glycocalix which is characteristic of each stage of the life cycle. Its composition and complexity depend mainly on mucin-like proteins. A remarkable feature of O-glycan biosynthesis in trypanosomes is that it initiates with the addition of a GlcNAc instead of the GalNAc residue that is commonly used in vertebrate mucins.

Mucin-type O-glycosylation in Mesocestoides vogae (syn. corti).

Protein glycosylation is an important post-translational modification underlying host-parasite interactions, which may determine the outcome of infection. Although Mesocestoides vogae represents an important model for investigating the various aspects of cestode biology, virtually no information is available about the structure and synthesis of glycans in this parasite. In this work, focused on the initiation pathway of mucin-type O-glycosylation in M.