125 results match your criteria tryparedoxin peroxidase


Leishmania donovani chaperonin TCP1γ subunit protects miltefosine induced oxidative damage.

Int J Biol Macromol 2020 Dec 22;165(Pt B):2607-2620. Epub 2020 Oct 22.

Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

T-complex protein-1 (TCP1) is a chaperonin protein known to fold various proteins like actin and tubulin. In Leishmania donovani only one subunit of TCP1 that is gamma subunit (LdTCP1γ) has been functionally characterized. It not only performs ATP dependent protein folding but is also essential for survival and virulence. Read More

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December 2020

Proteomic analysis reveals differentially abundant proteins probably involved in the virulence of amastigote and promastigote forms of Leishmania infantum.

Parasitol Res 2021 Feb 8;120(2):679-692. Epub 2021 Jan 8.

Laboratório de Leishmanioses, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, CEP: 31270-901, Brazil.

Owing to the importance and clinical diversity of Leishmania infantum, studying its virulence factors is promising for understanding the relationship between parasites and hosts. In the present study, differentially abundant proteins from strains with different degrees of virulence in promastigote and amastigote forms were compared using two quantitative proteomics techniques, differential gel electrophoresis and isobaric mass tag labeling, followed by identification by mass spectrometry. A total of 142 proteins were identified: 96 upregulated and 46 downregulated proteins in the most virulent strain compared to less virulent. Read More

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February 2021

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

Immunology 2021 May 25;163(1):46-59. Epub 2021 Jan 25.

Unidad de Biología Molecular, Institut Pasteur Montevideo, Montevideo, Uruguay.

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. Read More

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Metabolic Control Analysis for Drug Target Prioritization in Trypanosomatids.

Methods Mol Biol 2020 ;2116:689-718

Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, Mexico.

To validate therapeutic targets in metabolic pathways of trypanosomatids, the criterion of enzyme essentiality determined by gene knockout or knockdown is usually being applied. Since, it is often found that most of the enzymes/proteins analyzed are essential, additional criteria have to be implemented for drug target prioritization. Metabolic control analysis (MCA), often in conjunction with kinetic pathway modeling, offers such possibility for prioritization. Read More

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February 2021

Comparison of gene expression of pyruvate kinase and tryparedoxin peroxidase in metacyclic promastigote forms of Leishmania (L.) tropica and L. major by real-time PCR

Ann Parasitol 2020 ;66(1):13-18

Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Two predominant forms of cutaneous leishmaniosis are anthroponotic CL (ACL) and zoonotic CL (ZCL) caused by Leishmania (L.) tropica and L. major in Iran and many countries, respectively. Read More

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Identification of potential anti-leishmanial agents using computational investigation and biological evaluation against trypanothione reductase.

J Biomol Struct Dyn 2021 Feb 10;39(3):960-969. Epub 2020 Feb 10.

Molecular & Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow, India.

Trypanothione reductase of is a flavin adenine dinucleotide containing homodimeric protein essential for parasite survival. The flavoenzyme utilizes nicotinamide adenine dinucleotide phosphate in the reaction to convert oxidized trypanothione to reduced trypanothione which is further used up by tryparedoxin/tryparedoxin peroxidase system to neutralize the reactive oxygen species generated by the macrophages. Some of the drugs previously reported against the disease include sodium stibogluconate, miltefosine and amphotericin B. Read More

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February 2021

Functional insight into the glycosomal peroxiredoxin of Leishmania.

Acta Trop 2020 Jan 9;201:105217. Epub 2019 Oct 9.

i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.

Glycosomes of trypanosomatids are peroxisome-like organelles comprising unique metabolic features, among which the lack of the hallmark peroxisomal enzyme catalase. The absence of this highly efficient peroxidase from glycosomes is presumably compensated by other antioxidants, peroxidases of the peroxiredoxin (PRX) family being the most promising candidates for this function. Here, we follow on this premise and investigate the product of a Leishmania infantum gene coding for a putative glycosomal PRX (LigPRX). Read More

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January 2020

Oligomerization dynamics and functionality of Trypanosoma cruzi cytosolic tryparedoxin peroxidase as peroxidase and molecular chaperone.

Biochim Biophys Acta Gen Subj 2019 10 29;1863(10):1583-1594. Epub 2019 Jun 29.

Unidad de Biología Molecular, Institut Pasteur Montevideo, Montevideo, Uruguay; Sección Genética, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay. Electronic address:

Background: Trypanosoma cruzi cytosolic tryparedoxin peroxidase (c-TXNPx) is a 2-Cys peroxiredoxin that plays an important role in coping with host cell oxidative response during the infection process, for which it has been described as a virulence factor.

Methods: Four residues corresponding to c-TXNPx catalytic and solvent-exposed cysteines were individually mutated to serine by site-specific mutagenesis. Susceptibility to redox treatments and oligomeric dynamics were investigated by western-blot and gel filtration chromatography. Read More

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October 2019

Gamma-glutamylcysteine synthetase and tryparedoxin 1 exert high control on the antioxidant system in Trypanosoma cruzi contributing to drug resistance and infectivity.

Redox Biol 2019 09 28;26:101231. Epub 2019 May 28.

Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, 14080, Mexico. Electronic address:

Trypanothione (T(SH)) is the main antioxidant metabolite for peroxide reduction in Trypanosoma cruzi; therefore, its metabolism has attracted attention for therapeutic intervention against Chagas disease. To validate drug targets within the T(SH) metabolism, the strategies and methods of Metabolic Control Analysis and kinetic modeling of the metabolic pathway were used here, to identify the steps that mainly control the pathway fluxes and which could be appropriate sites for therapeutic intervention. For that purpose, gamma-glutamylcysteine synthetase (γECS), trypanothione synthetase (TryS), trypanothione reductase (TryR) and the tryparedoxin cytosolic isoform 1 (TXN1) were separately overexpressed to different levels in T. Read More

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September 2019

Structure-guided approach to identify a novel class of anti-leishmaniasis diaryl sulfide compounds targeting the trypanothione metabolism.

Amino Acids 2020 Feb 29;52(2):247-259. Epub 2019 Apr 29.

Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, IBPM-CNR, c/o Dip. Scienze Biochimiche Università Sapienza, P.le Aldo Moro 5, 00185, Rome, Italy.

Leishmania protozoans are the causative agent of leishmaniasis, a neglected tropical disease consisting of three major clinical forms: visceral leishmaniasis (VL), cutaneous leishmaniasis, and mucocutaneous leishmaniasis. VL is caused by Leishmania donovani in East Africa and the Indian subcontinent and by Leishmania infantum in Europe, North Africa, and Latin America, and causes an estimated 60,000 deaths per year. Trypanothione reductase (TR) is considered to be one of the best targets to find new drugs against leishmaniasis. Read More

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February 2020

Serine Proteinases in Leishmania (Viannia) braziliensis Promastigotes Have Distinct Subcellular Distributions and Expression.

Int J Mol Sci 2019 Mar 15;20(6). Epub 2019 Mar 15.

Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro 21040-900, Brazil.

Serine proteinases in promastigotes were assessed in this work. This study included the investigation of the enzymatic activity of subcellular fractions obtained from benzamidine affinity chromatography, reverse transcription polymerase chain reactions, and in silico assays of subcellular localization of subtilisin. Promastigote serine proteinases showed gelatinolytic activity with molecular masses of 43 kDa to 170 kDa in the cytosolic fraction and 67 kDa to 170 kDa in the membranous fraction. Read More

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An Insight into the Constitutive Proteome Throughout Leishmania donovani Promastigote Growth and Differentiation.

Int Microbiol 2019 Mar 16;22(1):143-154. Epub 2018 Nov 16.

Laboratory of Molecular Parasitology, Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (Consejo Superior de Investigaciones Científicas), Calle Ramiro de Maeztu 9, 28040, Madrid, Spain.

Anthroponotic visceral leishmaniasis is a life-threatening disease caused by Leishmania donovani (Kinetoplastida: Trypanosomatidae) in East Africa and the Indian subcontinent. Unlike promastigote growth and differentiation in the sand fly gut or in axenic culture, L. donovani promastigote-into-amastigote development has been studied by high-throughput gene expression profiling. Read More

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Identification and binding mode of a novel Leishmania Trypanothione reductase inhibitor from high throughput screening.

PLoS Negl Trop Dis 2018 11 26;12(11):e0006969. Epub 2018 Nov 26.

Istituto di Biologia e Patologia Molecolari-CNR, and Dipartimento di Scienze Biochimiche, "Sapienza" Università di Roma P.le A. Moro, Roma, Italy.

Trypanothione reductase (TR) is considered to be one of the best targets to find new drugs against Leishmaniasis. This enzyme is fundamental for parasite survival in the host since it reduces trypanothione, a molecule used by the tryparedoxin/tryparedoxin peroxidase system of Leishmania to neutralize hydrogen peroxide produced by host macrophages during infection. In order to identify new lead compounds against Leishmania we developed and validated a new luminescence-based high-throughput screening (HTS) assay that allowed us to screen a library of 120,000 compounds. Read More

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November 2018

Base excision repair plays an important role in the protection against nitric oxide- and in vivo-induced DNA damage in Trypanosoma brucei.

Free Radic Biol Med 2019 02 22;131:59-71. Epub 2018 Nov 22.

Instituto de Parasitología y Biomedicina "López-Neyra". Consejo Superior de Investigaciones Científicas. Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento, 17, 18016 Armilla, Granada, Spain. Electronic address:

Uracil-DNA glycosylase (UNG) initiates the base excision repair pathway by excising uracil from DNA. We have previously shown that Trypanosoma brucei cells defective in UNG exhibit reduced infectivity thus demonstrating the relevance of this glycosylase for survival within the mammalian host. In the early steps of the immune response, nitric oxide (NO) is released by phagocytes, which in combination with oxygen radicals produce reactive nitrogen species (RNS). Read More

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February 2019

Tryparedoxin peroxidase-deficiency commits trypanosomes to ferroptosis-type cell death.

Elife 2018 07 26;7. Epub 2018 Jul 26.

Biochemie-Zentrum der Universität Heidelberg, Heidelberg, Germany.

Tryparedoxin peroxidases, distant relatives of glutathione peroxidase 4 in higher eukaryotes, are responsible for the detoxification of lipid-derived hydroperoxides in African trypanosomes. The lethal phenotype of procyclic that lack the enzymes fulfils all criteria defining a form of regulated cell death termed ferroptosis. Viability of the parasites is preserved by α-tocopherol, ferrostatin-1, liproxstatin-1 and deferoxamine. Read More

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Evaluation of the immune response against Trypanosoma cruzi cytosolic tryparedoxin peroxidase in human natural infection.

Immunology 2018 11 3;155(3):367-378. Epub 2018 Aug 3.

Laboratorio de Inmunología de las Infecciones por Tripanosomátidos, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET), Buenos Aires, Argentina.

Trypanosoma cruzi, the aetiological agent of Chagas disease, has a highly efficient detoxification system to deal with the oxidative burst imposed by its host. One of the antioxidant enzymes involved is the cytosolic tryparedoxin peroxidase (c-TXNPx), which catalyses the reduction to hydrogen peroxide, small-chain organic hydroperoxides and peroxynitrite. This enzyme is present in all parasite stages, and its overexpression renders parasites more resistant to the oxidative defences of macrophages, favouring parasite survival. Read More

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November 2018

Trypanosoma cruzi: analysis of two different strains after piplartine treatment.

Braz J Infect Dis 2018 May - Jun;22(3):208-218. Epub 2018 Jun 5.

Universidade Estadual Paulista - UNESP, Faculdade de Ciências Farmacêuticas, Araraquara, SP, Brazil. Electronic address:

The hemoflagellate protozoan, Trypanosoma cruzi, mainly transmitted by triatomine insects through blood transfusion or from mother-to-child, causes Chagas' disease. This is a serious parasitic disease that occurs in Latin America, with considerable social and economic impact. Nifurtimox and benznidazole, drugs indicated for treating infected persons, are effective in the acute phase, but poorly effective during the chronic phase. Read More

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Cytosolic tryparedoxin of Leishmania donovani modulates host immune response in visceral leishmaniasis.

Cytokine 2018 08 16;108:1-8. Epub 2018 Mar 16.

Laboratory of Molecular Biochemistry and Cell Biology, Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Agumkuan, Patna 800007, India. Electronic address:

Leishmaniasis is a neglected tropical disease caused by the unicellular protozoan parasite of genus Leishmania. Tryparedoxin (TXN) is a low molecular mass dithiol protein belonging to oxidoreductases super-family; which function in concert with tryparedoxin peroxidase (TXNPx) as a system in protozoan parasites including Leishmania. Leishmanial hydroperoxides detoxification cascade uses trypanothione as electron donor to reduce hydroperoxide inside the macrophages during infection. Read More

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Quantitative proteomic analysis of amastigotes from Leishmania (L.) amazonensis LV79 and PH8 strains reveals molecular traits associated with the virulence phenotype.

PLoS Negl Trop Dis 2017 Nov 27;11(11):e0006090. Epub 2017 Nov 27.

Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Background: Leishmaniasis is an antropozoonosis caused by Leishmania parasites that affects around 12 million people in 98 different countries. The disease has different clinical forms, which depend mainly on the parasite genetics and on the immunologic status of the host. The promastigote form of the parasite is transmitted by an infected female phlebotomine sand fly, is internalized by phagocytic cells, mainly macrophages, and converts into amastigotes which replicate inside these cells. Read More

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November 2017

Trypanosoma cruzi tryparedoxin II interacts with different peroxiredoxins under physiological and oxidative stress conditions.

Exp Parasitol 2018 Jan 21;184:1-10. Epub 2017 Nov 21.

Departamento de Bioquímica e Biologia Tecidual, UNICAMP, Campinas, SP, Brazil. Electronic address:

Trypanosoma cruzi, the etiologic agent of Chagas disease, has to cope with reactive oxygen and nitrogen species during its life cycle in order to ensure its survival and infection. The parasite detoxifies these species through a series of pathways centered on trypanothione that depend on glutathione or low molecular mass dithiol proteins such as tryparedoxins. These proteins transfer reducing equivalents to peroxidases, including mitochondrial and cytosolic peroxiredoxins, TcMPx and TcCPx, respectively. Read More

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January 2018

Dataset generated for Dissection of mechanisms of Trypanothione Reductase and Tryparedoxin Peroxidase through dynamic network analysis and simulations in leishmaniasis.

Data Brief 2017 Dec 19;15:757-769. Epub 2017 Oct 19.

National Centre for Cell Science, NCCS Complex, Ganeshkhind, SP Pune University Campus, Pune 411007, India.

Leishmaniasis is the second largest parasitic killer disease caused by the protozoan parasite , transmitted by the bite of sand flies. It's endemic in the eastern India with 165.4 million populations at risk with the current drug regimen. Read More

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December 2017

Functional Involvement of Leishmania donovani Tryparedoxin Peroxidases during Infection and Drug Treatment.

Antimicrob Agents Chemother 2018 01 21;62(1). Epub 2017 Dec 21.

Cell Death and Differentiation Research, National Institute of Immunology, New Delhi, India

The parasite causes visceral leishmaniasis, a potentially fatal disease. The parasites survive within mammalian macrophages and express a unique set of enzymes, the tryparedoxin peroxidases, for their defense against oxidative stress generated by the host. In this study, we demonstrate different roles of two distinct enzymes, the mitochondrial tryparedoxin peroxidase (mTXNPx) and the cytosolic tryparedoxin peroxidase (cTXNPx), in defending the parasites against mitochondrial and exogenous oxidative stress during infection and drug treatment. Read More

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January 2018

Trans-sialidase overcomes many antigens to be used as a vaccine candidate against Trypanosoma cruzi.

Immunotherapy 2017 06;9(7):555-565

Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Argentina.

Aim: The development of vaccines against Trypanosoma cruzi remains in an exploratory stage. Despite several antigen candidates have been evaluated, a comparison among the performance of the immunogens cannot be carried out because the available reports differ in formulations and infection model. In this work, we compared the protective capacity of seven T. Read More

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Identification of potential protein partners that bind to the variant surface glycoprotein in Trypanosoma equiperdum.

Parasitology 2017 Jun 10;144(7):923-936. Epub 2017 Feb 10.

Departamento de Biología Celular,Universidad Simón Bolívar,Caracas,Venezuela.

Trypanosoma equiperdum possesses a dense coat of a variant surface glycoprotein (VSG) that is used to evade the host immune response by a process known as antigenic variation. Soluble and membrane forms of the predominant VSG from the Venezuelan T. equiperdum TeAp-N/D1 strain (sVSG and mVSG, respectively) were purified to homogeneity; and antibodies against sVSG and mVSG were raised, isolated, and employed to produce anti-idiotypic antibodies that structurally mimic the VSG surface. Read More

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Differential expression on mitochondrial tryparedoxin peroxidase (mTcTXNPx) in Trypanosoma cruzi after ferrocenyl diamine hydrochlorides treatments.

Braz J Infect Dis 2017 Mar - Apr;21(2):125-132. Epub 2016 Dec 2.

Universidade Estadual Paulista Júlio de Mesquita Filho, Laboratório de Imunologia e Biologia Molecular, Departamento de Ciências Biológicas, Araraquara, SP, Brazil. Electronic address:

Resistance to benznidazole in certain strains of Trypanosoma cruzi may be caused by the increased production of enzymes that act on the oxidative metabolism, such as mitochondrial tryparedoxin peroxidase which catalyses the reduction of peroxides. This work presents cytotoxicity assays performed with ferrocenyl diamine hydrochlorides in six different strains of T. cruzi epimastigote forms (Y, Bolivia, SI1, SI8, QMII, and SIGR3). Read More

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Increased Abundance of Proteins Involved in Resistance to Oxidative and Nitrosative Stress at the Last Stages of Growth and Development of Leishmania amazonensis Promastigotes Revealed by Proteome Analysis.

PLoS One 2016 24;11(10):e0164344. Epub 2016 Oct 24.

Departamento de Microbiología Molecular y Biología de las Infecciones y Servicio de Proteómica y Genómica, Centro de Investigaciones Biológicas (Consejo Superior de Investigaciones Científicas), Calle Ramiro de Maeztu 9, 28040, Madrid, Spain.

Leishmania amazonensis is one of the major etiological agents of the neglected, stigmatizing disease termed american cutaneous leishmaniasis (ACL). ACL is a zoonosis and rodents are the main reservoirs. Most cases of ACL are reported in Brazil, Bolivia, Colombia and Peru. Read More

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Current Therapeutics, Their Problems and Thiol Metabolism as Potential Drug Targets in Leishmaniasis.

Curr Drug Metab 2016 ;17(9):897-919

Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, 800007, India.

Leishmaniasis is one of the six diseases regarded most neglected by World Health Organization which is predominant in developing countries. Clinically, among the different forms of leishmaniasis, visceral leishmaniasis is the most fatal, serious disease, in which several organs of the body such as liver and spleen are affected. A limited number of drugs against leishmaniasis are available for the treatment and also, no suitable vaccine is available for the control of leishmaniasis. Read More

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February 2017

Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum.

Int J Parasitol Drugs Drug Resist 2016 08 4;6(2):133-9. Epub 2016 Jun 4.

Instituto de Parasitología y Biomedicina "López-Neyra", CSIC, (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud, Granada, Spain. Electronic address:

Visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, is one of the most important zoonotic diseases affecting dogs and humans in the Mediterranean area. The presence of infected dogs as the main reservoir host of L. infantum is regarded as the most significant risk for potential human infection. Read More

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Catalytic properties, localization, and in vivo role of Px IV, a novel tryparedoxin peroxidase of Trypanosoma brucei.

Mol Biochem Parasitol 2016 06 1;207(2):84-8. Epub 2016 Jun 1.

Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany. Electronic address:

Px IV is a distant relative of the known glutathione peroxidase-type enzymes of African trypanosomes. Immunofluorescence microscopy of bloodstream cells expressing C-terminally Myc6-tagged Px IV revealed a mitochondrial localization. Recombinant Px IV possesses very low activity as glutathione peroxidase but catalyzes the trypanothione/tryparedoxin-dependent reduction of hydrogen peroxide and, even more efficiently, of arachidonic acid hydroperoxide. Read More

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TcI Isolates of Trypanosoma cruzi Exploit the Antioxidant Network for Enhanced Intracellular Survival in Macrophages and Virulence in Mice.

Infect Immun 2016 06 24;84(6):1842-1856. Epub 2016 May 24.

Department of Pathology, School of Medicine, University of Texas Medical Branch Galveston, Galveston, Texas, USA

Trypanosoma cruzi species is categorized into six discrete typing units (TcI to TcVI) of which TcI is most abundantly noted in the sylvatic transmission cycle and considered the major cause of human disease. In our study, the TcI strains Colombiana (COL), SylvioX10/4 (SYL), and a cultured clone (TCC) exhibited different biological behavior in a murine model, ranging from high parasitemia and symptomatic cardiomyopathy (SYL), mild parasitemia and high tissue tropism (COL), to no pathogenicity (TCC). Proteomic profiling of the insect (epimastigote) and infective (trypomastigote) forms by two-dimensional gel electrophoresis/matrix-assisted laser desorption ionization-time of flight mass spectrometry, followed by functional annotation of the differential proteome data sets (≥2-fold change, P < 0. Read More

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