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Tag: Trypanosoma cruzi

Identification and Localization of the First Known Proteins of the Trypanosoma cruzi Cytostome Cytopharynx Endocytic Complex

Donna Huber on January 17, 2020

The etiological agent of Chagas disease, Trypanosoma cruzi, is an obligate intracellular parasite that infects an estimated 7 million people in the Americas, with an at-risk population of 70 million. Despite its recognition as the highest impact parasitic infection of the Americas, Chagas disease continues to receive insufficient attention and resources in order to be effectively …

Chagas Disease Drug Discovery: Multiparametric Lead Optimization against Trypanosoma cruzi in Acylaminobenzothiazole Series

Donna Huber on November 18, 2019

Acylaminobenzothiazole hits were identified as potential inhibitors of Trypanosoma cruzi replication, a parasite responsible for Chagas disease. We selected compound 1 for lead optimization, aiming to improve in parallel its anti-T. cruzi activity (IC50 = 0.63 μM) and its human metabolic stability (human clearance = 9.57 mL/min/g). A total of 39 analogues of 1 were synthesized and tested in vitro. We established a …

Functional analysis and importance for host cell infection of the Ca2+-conducting subunits of the mitochondrial calcium uniporter of Trypanosoma cruzi

Donna Huber on May 15, 2019

We report here that Trypanosoma cruzi, the etiologic agent of Chagas disease, possesses two unique paralogs of the mitochondrial calcium uniporter complex TcMCU subunit that we named TcMCUc, and TcMCUd. The predicted structure of the proteins indicates that, as that predicted for the TcMCU and TcMCUb paralogs, they are composed of two helical membrane-spanning domains, and contain a WDXXEPXXY motif. Overexpression of each gene led …

MICU1 and MICU2 Play an Essential Role in Mitochondrial Ca2+ Uptake, Growth, and Infectivity of the Human Pathogen Trypanosoma cruzi

Donna Huber on May 7, 2019

The mitochondrial Ca2+ uptake in trypanosomatids, which belong to the eukaryotic supergroup Excavata, shares biochemical characteristics with that of animals, which, together with fungi, belong to the supergroup Opisthokonta. However, the composition of the mitochondrial calcium uniporter (MCU) complex in trypanosomatids is quite peculiar, suggesting lineage-specific adaptations. In this work, we used Trypanosoma cruzi to study the role …

Genome Editing by CRISPR/Cas9 in Trypanosoma cruzi

Donna Huber on March 15, 2019

The genetic manipulation of the human parasite Trypanosoma cruzi has been significantly improved since the implementation of the CRISPR/Cas9 system for genome editing in this organism. The system was initially used for gene knockout in T. cruzi, later on for endogenous gene tagging and more recently for gene complementation. Mutant cell lines obtained by CRISPR/Cas9 have been …

Further insights of selenium-containing analogues of WC-9 against Trypanosoma cruzi

Donna Huber on February 28, 2019

As a continuation of our project aimed at searching for new chemotherapeutic agents against American trypanosomiasis (Chagas disease), new selenocyanate derivatives were designed, synthesized and biologically evaluated against the clinically more relevant dividing form of Trypanosoma cruzi, the etiologic agent of this illness. In addition, in order to establish the role of each part of …

Trypanosoma cruzi 13C-labeled O-Glycan standards for mass spectrometry

Donna Huber on January 12, 2019

Abstract Trypanosoma cruzi is a protozoan parasite that causes Chagas disease, a debilitating condition that affects over 10 million humans in the American continents. In addition to its traditional mode of human entry via the ‘kissing bug’ in endemic areas, the infection can also be spread in non-endemic countries through blood transfusion, organ transplantation, eating food …

New method patented to provide increased vaccine efficacy

Donna Huber on November 13, 2018

by Donna Huber Vaccines can be an efficient and cost-effective method of preventing and treating pathogen-induced illnesses. As new pathogens appear and old pathogens re-emerge, improved vaccines are needed. For one emerging global disease, Chagas Disease, effective vaccine development has long been elusive. Now, Rick Tarleton, Regents’ Professor in the department of cellular biology, and former …

Highly competent, non-exhausted CD8+ T cells continue to tightly control pathogen load throughout chronic Trypanosoma cruzi infection

Donna Huber on November 12, 2018

Abstract Trypanosoma cruzi infection is characterized by chronic parasitism of non-lymphoid tissues and is rarely eliminated despite potent adaptive immune responses. This failure to cure has frequently been attributed to a loss or impairment of anti-T. cruzi T cell responses over time, analogous to the T cell dysfunction described for other persistent infections. In this study, we have …

Calcium-sensitive pyruvate dehydrogenase phosphatase is required for energy metabolism, growth, differentiation, and infectivity of Trypanosoma cruzi

Donna Huber on September 19, 2018

Abstract In vertebrate cells, mitochondrial Ca2+ uptake by the mitochondrial calcium uniporter (MCU) leads to Ca2+-mediated stimulation of an intramitochondrial pyruvate dehydrogenase phosphatase (PDP). This enzyme dephosphorylates serine residues in the E1α subunit of pyruvate dehydrogenase (PDH), thereby activating PDH and resulting in increased ATP production. Although a phosphorylation–dephosphorylation cycle for the E1α subunit of …