<i>Trypanosoma cruzi</i> Coexpressing Ornithine Decarboxylase and Green Fluorescence Proteins as a Tool to Study the Role of Polyamines in Chagas Disease Pathology

Barclay, Jeremías José; Morosi, Luciano Gastón; Vanrell, María Cristina; Trejo, Edith Corina; Romano, Patricia Silvia; Carrillo, Carolina

doi:10.4061/2011/657460

Cited by 14 publications

(21 citation statements)

References 69 publications

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“…Y strain T. cruzi epimastigotes expressing green fluorescent protein (GFP) (Y‐GFP) (kindly provided by Dr. S. Schenkman, Universidade Federal de Sao Paulo (Sao Paulo, Brazil)) were maintained in Diamond medium (0.1 M NaCl, 0.05 M K 2 HPO 4 pH 7.2, 0.625% tryptose, 0.625% tryptone, 0.625% yeast extract, 12.5 μg/mL Hemin) supplemented with 10% inactivated fetal bovine serum (Gibco), at 28 °C. Y‐GFP trypomastigotes were obtained by in vitro metacyclogenesis of epimastigotes as described [15] and maintained in culture of Vero cells in DMEM supplemented with 3% fetal bovine serum (FBS) and antibiotics at 37 °C in an atmosphere of 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition

et al. 2014

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CYP51 (sterol 14α-demethylase) is an efficient target for clinical and agricultural antifungals and an emerging target for treatment of Chagas disease, the infection that is caused by multiple strains of a protozoan pathogen Trypanosoma cruzi. Here, we analyze CYP51A from the Y strain T. cruzi. In this protein, proline 355, a residue highly conserved across the CYP51 family, is replaced with serine. The purified enzyme retains its catalytic activity, yet has been found less susceptible to inhibition. These biochemical data are consistent with cellular experiments, both in insect and human stages of the pathogen. Comparative structural analysis of CYP51 complexes with VNI and two derivatives suggests that broad-spectrum CYP51 inhibitors are likely to be preferable as antichagasic drug candidates.

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Section: Methodsmentioning

confidence: 99%

Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition

et al. 2014

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“…In this pathway, parasites invade cells and are initially housed in autophagocytic vacuoles, which eventually fuse with lysosomes to create an acidic autophagolysosomal compartment. These vacuoles are thought to be rich in nutrients for parasite survival and polyamines which promote differentiation of trypomastigotes into amastigotes[141]. Overall, this last model is probably a modified version of the lysosomalindependent pathway specialized for conditions of starvation.…”

Section: Mechanisms Of Host Cell Invasion By Trypanosoma Cruzimentioning

confidence: 99%

Mechanisms of cellular invasion by intracellular parasites

Walker

Oghumu

Gupta

et al. 2013

Cell. Mol. Life Sci.

146

108

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Numerous disease-causing parasites must invade host cells to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population.Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis.This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites

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“…cruzi infection [40]. Hence, we evaluated the effect of flavins on these processes in an in vitro infection model ( Fig 5D ).…”

Section: Resultsmentioning

confidence: 99%

The superfamily keeps growing: Identification in trypanosomatids of RibJ, the first riboflavin transporter family in protists

et al. 2017

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BackgroundTrypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors. While metazoans obtain riboflavin from the diet through RFVT/SLC52 transporters, the riboflavin transport mechanisms in trypanosomatids still remain unknown.Methodology/Principal findingsHere, we show that riboflavin is imported with high affinity in Trypanosoma cruzi, Trypanosoma brucei, Leishmania (Leishmania) mexicana, Crithidia fasciculata and Phytomonas Jma using radiolabeled riboflavin transport assays. The vitamin is incorporated through a saturable carrier-mediated process. Effective competitive uptake occurs with riboflavin analogs roseoflavin, lumiflavin and lumichrome, and co-factor derivatives FMN and FAD. Moreover, important biological processes evaluated in T. cruzi (i.e. proliferation, metacyclogenesis and amastigote replication) are dependent on riboflavin availability. In addition, the riboflavin competitive analogs were found to interfere with parasite physiology on riboflavin-dependent processes. By means of bioinformatics analyses we identified a novel family of riboflavin transporters (RibJ) in trypanosomatids. Two RibJ members, TcRibJ and TbRibJ from T. cruzi and T. brucei respectively, were functionally characterized using homologous and/or heterologous expression systems.Conclusions/SignificanceThe RibJ family represents the first riboflavin transporters found in protists and the third eukaryotic family known to date. The essentiality of riboflavin for trypanosomatids, and the structural/biochemical differences that RFVT/SLC52 and RibJ present, make the riboflavin transporter -and its downstream metabolism- a potential trypanocidal drug target.

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Trypanosoma cruzi Coexpressing Ornithine Decarboxylase and Green Fluorescence Proteins as a Tool to Study the Role of Polyamines in Chagas Disease Pathology

Cited by 14 publications

References 69 publications

Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition

Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition

Mechanisms of cellular invasion by intracellular parasites

The superfamily keeps growing: Identification in trypanosomatids of RibJ, the first riboflavin transporter family in protists

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