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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 …

The Toxoplasma Vacuolar H+-ATPase Regulates Intracellular pH and Impacts the Maturation of Essential Secretory Proteins

Donna Huber on May 14, 2019

Vacuolar-proton ATPases (V-ATPases) are conserved complexes that couple the hydrolysis of ATP to the pumping of protons across membranes. V-ATPases are known to play diverse roles in cellular physiology. We studied the Toxoplasma gondiiV-ATPase complex and discovered a dual role of the pump in protecting parasites against ionic stress and in the maturation of secretory proteins in …

The ER chaperone PfGRP170 is essential for asexual development and is linked to stress response in malaria parasites

Donna Huber on May 14, 2019

The vast majority of malaria mortality is attributed to one parasite species: Plasmodium falciparum. Asexual replication of the parasite within the red blood cell is responsible for the pathology of the disease. In Plasmodium, the endoplasmic reticulum (ER) is a central hub for protein folding and trafficking as well as stress response pathways. In this study, we tested …

Toll family members bind multiple Spätzle proteins and activate antimicrobial peptide gene expression in Drosophila

Donna Huber on May 14, 2019

This illustration depicts a dorsal view of the “common” fruit fly, or “vinegar” fly, Drosophila melanogaster.Courtesy of Public Health Image Library The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spätzle (Spz-1), but Drosophila encodes …

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 …

Distinct amino acid and lipid perturbations characterize acute versus chronic malaria

Donna Huber on May 2, 2019

Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not known. Here, with the goal of …

NUDIX hydrolases with inorganic polyphosphate exo- and endo-polyphosphatase activities in the glycosome, cytosol and nucleus of Trypanosoma brucei

Donna Huber on May 1, 2019

Trypanosoma brucei, a protist parasite that causes African trypanosomiasis or sleeping sickness, relies mainly on glycolysis for ATP production when in its mammalian host. Glycolysis occurs within a peroxisome-like organelle named the glycosome. Previous work from our laboratory reported the presence of significant amounts of inorganic polyphosphate (polyP), a polymer of three to hundreds of orthophosphate …

Macrocyclic lactone anthelmintic-induced leukocyte binding to Dirofilaria immitis microfilariae: Influence of the drug resistance status of the parasite

Donna Huber on April 26, 2019

The macrocyclic lactone anthelmintics are the only class of drug currently used to prevent heartworm disease. Their extremely high potency in vivo is not mirrored by their activity against Dirofilaria immitis larvae in vitro, leading to suggestions that they may require host immune functions to kill the parasites. We have previously shown that ivermectin stimulates …

Evolution of Cryptosporidium

Donna Huber on April 25, 2019

A large-scale comparative genomic survey of Cryptosporidium species and subtypes reveals a cryptic anthroponotic Cryptosporidium parvum branch and a large, recent superclade of species and subtypes that undergo genetic exchange, potentially facilitating host associations. Jessica C. Kissinger. 2019. Nature Microbiology; 4: 730–731. https://www.nature.com/articles/s41564-019-0438-1

Multiple Praziquantel Treatments of Schistosoma mansoni Egg-Negative, CCA-Positive Schoolchildren in a Very Low Endemic Setting in Egypt Do Not Consistently Alter CCA Results

Donna Huber on April 22, 2019

Forty-four Schistosoma mansoni egg-negative/circulating cathodic antigen (CCA) low-positive (trace or 1+) children in three districts of very low prevalence in Egypt were given three sequential praziquantel (PZQ) treatments. Stool and urine specimens were collected 3 months following the initial treatment, and 3 weeks following the second and following the third PZQ treatments, which were conducted 5 weeks …

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