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Category: publications

Analysis of the Interactome of the Toxoplasma gondii Tgj1 HSP40 Chaperone

Donna Huber on March 1, 2023

Toxoplasma gondii is an obligate intracellular apicomplexan that causes toxoplasmosis in humans and animals. Central to its dissemination and pathogenicity is the ability to rapidly divide in the tachyzoite stage and infect any type of nucleated cell. Adaptation to different cell contexts requires high plasticity in which heat shock proteins (Hsps) could play a fundamental role. …

An X-Domain Phosphoinositide Phospholipase C (PI-PLC-like) of Trypanosoma brucei Has a Surface Localization and Is Essential for Proliferation

Donna Huber on February 28, 2023

Trypanosoma brucei is the causative agent of African trypanosomiasis, a deadly disease that affects humans and cattle. There are very few drugs to treat it, and there is evidence of mounting resistance, raising the need for new drug development. Here, we report the presence of a phosphoinositide phospholipase C (TbPI-PLC-like), containing an X and a PDZ …

First bovine vaccine to prevent human schistosomiasis – a cluster randomised Phase 3 clinical trial

Donna Huber on February 21, 2023

Objective Schistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, …

Chemical Optimization of CBL0137 for Human African Trypanosomiasis Lead Drug Discovery

Donna Huber on January 25, 2023

The carbazole CBL0137 (1) is a lead for drug development against human African trypanosomiasis (HAT), a disease caused by Trypanosoma brucei. To advance 1 as a candidate drug, we synthesized new analogs that were evaluated for the physicochemical properties, antitrypanosome potency, selectivity against human cells, metabolism in microsomes or hepatocytes, and efflux ratios. Structure-activity/property analyses of analogs revealed …

TriTrypDB: An integrated functional genomics resource for kinetoplastida

Donna Huber on January 19, 2023

Parasitic diseases caused by kinetoplastid parasites are a burden to public health throughout tropical and subtropical regions of the world. TriTrypDB (https://tritrypdb.org) is a free online resource for data mining of genomic and functional data from these kinetoplastid parasites and is part of the VEuPathDB Bioinformatics Resource Center (https://veupathdb.org). As of release 59, TriTrypDB hosts …

Praziquantel target validation of a Ca2+ permeable channel in schistosomes

Donna Huber on January 18, 2023

Highlights Schistosomiasis is a devastating neglected helminthic disease. Praziquantel (PZQ) is the most important drug against schistosomiasis. Previous work identified a TRP channel of the melastatin type as a PZQ target. Molecular studies now reveal the basis for varied PZQ sensitivity of different helminths. Roberto Docampo. Cell Calcium. 2023 Jan 18;110:102698. doi: 10.1016/j.ceca.2023.102698

Malaria disrupts the rhesus macaque gut microbiome

Donna Huber on January 13, 2023

Previous studies have suggested that a relationship exists between severity and transmissibility of malaria and variations in the gut microbiome, yet only limited information exists on the temporal dynamics of the gut microbial community during a malarial infection. Here, using a rhesus macaque model of relapsing malaria, we investigate how malaria affects the gut microbiome. …

Epitopes in the Glycosylphosphatidylinositol Attachment Signal Peptide of Trypanosoma cruzi Mucin Proteins Generate Robust But Delayed and Nonprotective CD8+ T Cell Responses

Donna Huber on January 4, 2023

Infection with the protozoan parasite Trypanosoma cruzi elicits substantial CD8+ T cell responses that disproportionately target epitopes encoded in the large trans-sialidase (TS) gene family. Within the C57BL/6 infection model, a significant proportion (30-40%) of the T. cruzi-specific CD8+ T cell response targets two immunodominant TS epitopes, TSKb18 and TSKb20. However, both TS-specific CD8+ T …

AIM2 sensors mediate immunity to Plasmodium infection in hepatocytes

Donna Huber on January 3, 2023

Malaria, caused by Plasmodium parasites is a severe disease affecting millions of people around the world. Plasmodium undergoes obligatory development and replication in the hepatocytes, before initiating the life-threatening blood-stage of malaria. Although the natural immune responses impeding Plasmodium infection and development in the liver are key to controlling clinical malaria and transmission, those remain relatively unknown. Here we demonstrate that …