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Synthesis and biological evaluation of 1-alkylaminomethyl-1,1-bisphosphonic acids against Trypanosoma cruzi and Toxoplasma gondii

Donna Huber on July 4, 2019

As an extension of our project aimed at the search for new chemotherapeutic agents against Chagas disease and toxoplasmosis, several 1,1-bisphosphonates were designed, synthesized and biologically evaluated against Trypanosoma cruzi and Toxoplasma gondii, the etiologic agents of these diseases, respectively. In particular, and based on the antiparasitic activity exhibited by 2-alkylaminoethyl-1,1-bisphosphonates targeting farnesyl diphosphate synthase, a series of …

A Genetically Tractable, Natural Mouse Model of Cryptosporidiosis Offers Insights into Host Protective Immunity

Donna Huber on June 18, 2019

Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, and growth faltering. Older children in high endemicity regions appear resistant to infection, while previously unexposed adults remain susceptible. Experimental studies in humans and animals support the development of disease resistance, but we do not understand the mechanisms …

Microclimate and Larval Habitat Density Predict Adult Aedes albopictus Abundance in Urban Areas

Donna Huber on June 10, 2019

The Asian tiger mosquito, Aedes albopictus, transmits several arboviruses of public health importance, including chikungunya and dengue. Since its introduction to the United States in 1985, the species has invaded more than 40 states, including temperate areas not previously at risk of Aedes-transmitted arboviruses. Mathematical models incorporate climatic variables in predictions of site-specific Ae. albopictus abundances to identify …

Polydnaviruses: Evolution and Function

Donna Huber on June 6, 2019

Polydnaviruses (PDVs) were originally viewed as large DNA viruses that are beneficial symbionts of parasitoid wasps. Two groups of PDVs were also recognized: bracoviruses (BVs), which are associated with wasps in the family Braconidae, and ichnoviruses (IVs), which are associated with wasps in the family Ichneumonidae. Results to date indicate that BVs are endogenous virus …

An ortholog of Plasmodium falciparum chloroquine resistance transporter (PfCRT) plays a key role in maintaining the integrity of the endolysosomal system in Toxoplasma gondii to facilitate host invasion

Donna Huber on June 6, 2019

Toxoplasma gondii is an apicomplexan parasite with the ability to use foodborne, zoonotic, and congenital routes of transmission that causes severe disease in immunocompromised patients. The parasites harbor a lysosome-like organelle, termed the "Vacuolar Compartment/Plant-Like Vacuole" (VAC/PLV), which plays an important role in maintaining the lytic cycle and virulence of T. gondii. The VAC supplies proteolytic enzymes that …

Composition of the gut microbiota transcends genetic determinants of malaria infection severity and influences pregnancy outcome

Donna Huber on May 31, 2019

Background Malaria infection in pregnancy is a major cause of maternal and foetal morbidity and mortality worldwide. Mouse models for gestational malaria allow for the exploration of the mechanisms linking maternal malaria infection and poor pregnancy outcomes in a tractable model system. The composition of the gut microbiota has been shown to influence susceptibility to …

Blood feeding activates the vitellogenic stage of oogenesis in the mosquito Aedes aegypti through inhibition of glycogen synthase kinase 3 by the insulin and TOR pathways

Donna Huber on May 30, 2019

Most mosquitoes, including Aedes aegypti, only produce eggs after blood feeding on a vertebrate host. Oogenesis in A. aegypti consists of a pre-vitellogenic stage before blood feeding and a vitellogenic stage after blood feeding. Primary egg chambers remain developmentally arrested during the pre-vitellogenic stage but complete oogenesis to form mature eggs during the vitellogenic stage. In contrast, the signaling …

Bacteriophage acquisition restores protective mutualism

Donna Huber on May 29, 2019

Insects are frequently infected with inherited facultative symbionts known to provide a range of conditionally beneficial services, including host protection. Pea aphids (Acyrthosiphon pisum) often harbour the bacterium Hamiltonella defensa, which together with its associated bacteriophage A. pisum secondary endosymbiont (APSE) confer protection against an important natural enemy, the parasitic wasp Aphidius ervi. Previous studies showed that spontaneous loss …

The acidocalcisome inositol-1,4,5-trisphosphate receptor of Trypanosoma brucei is stimulated by luminal polyphosphate hydrolysis products

Donna Huber on May 28, 2019

Acidocalcisomes are acidic calcium stores rich in polyphosphate (polyP) and are present in trypanosomes and also in a diverse range of other organisms. Ca2+ is released from these organelles through a channel, inositol 1,4,5-trisphosphate receptor (TbIP3R), which is essential for growth and infectivity of the parasite Trypanosoma brucei. However, the mechanism by which TbIP3R controls …

Nucleocytoplasmic O-glycosylation in protists

Donna Huber on May 22, 2019

O-Glycosylation is an increasingly recognized modification of intracellular proteins in all kingdoms of life, and its occurrence in protists has been investigated to understand its evolution and its roles in the virulence of unicellular pathogens. We focus here on two kinds of glycoregulation found in unicellular eukaryotes: one is a simple O-fucose modification of dozens if …

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