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Category: publications

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

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

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

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

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

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

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

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 …

Field Testing Integrated Interventions for Schistosomiasis Elimination in the People’s Republic of China: Outcomes of a Multifactorial Cluster-Randomized Controlled Trial

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor Schistosoma japonicuminfections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future …

Pyrophosphate Stimulates the Phosphate-Sodium Symporter of Trypanosoma brucei Acidocalcisomes and Saccharomyces cerevisiae Vacuoles

Inorganic pyrophosphate (PPi) is a by-product of biosynthetic reactions and has bioenergetic and regulatory roles in a variety of cells. Here we show that PPi and other pyrophosphate-containing compounds, including polyphosphate (polyP), can stimulate sodium-dependent depolarization of the membrane potential and Pi conductance in Xenopus oocytes expressing a Saccharomyces cerevisiae or Trypanosoma brucei Na+/Pi symporter. PPi is not taken up by Xenopus oocytes, and deletion of the …

Diagnosis of Schistosoma mansoni infections: what are the choices in Brazilian low-endemic areas?

The population of Brazil is currently characterised by many individuals harbouring low-intensity Schistosoma mansoni infections. The Kato-Katz technique is the diagnostic method recommended by the World Health Organization (WHO) to assess these infections, but this method is not sensitive enough in the context of low egg excretion. In this regard, potential alternatives are being employed …