A5022821871- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Neurological diseases and metabolism
- Autophagy in Disease and Therapy
- Mosquito-borne diseases and control
- Parasitic Infections and Diagnostics
- Aquaculture disease management and microbiota
- RNA and protein synthesis mechanisms
- Viral gastroenteritis research and epidemiology
- Calpain Protease Function and Regulation
- Metabolism and Genetic Disorders
- Pharmacogenetics and Drug Metabolism
- Polyamine Metabolism and Applications
- Malaria Research and Control
- Invertebrate Immune Response Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- CRISPR and Genetic Engineering
- Biotin and Related Studies
- Endoplasmic Reticulum Stress and Disease
- Rabies epidemiology and control
- Hormonal Regulation and Hypertension
- Bacteriophages and microbial interactions
- Microbial Metabolism and Applications
- Reproductive System and Pregnancy
University of Geneva
2017-2024
University of Perugia
2015-2022
Merck & Co., Inc., Rahway, NJ, USA (United States)
2019
University of Kassel
2019
Cyclerion (United States)
2019
London School of Hygiene & Tropical Medicine
2019
Swiss National Science Foundation
2019
Toxoplasma gondii possesses sets of dense granule proteins (GRAs) that either assemble at, or cross the parasitophorous vacuole membrane (PVM) and exhibit motifs resembling HT/PEXEL previously identified in a repertoire exported Plasmodium proteins. Within spp., cleavage motif by endoplasmic reticulum-resident protease Plasmepsin V precedes trafficking to export across PVM involved pathogenicity host cell remodelling. Here, we have functionally characterized T. aspartyl 5 (ASP5),...
Abstract In Apicomplexa, rhoptry discharge is essential for invasion and involves an apical vesicle (AV) docking one or two rhoptries to a macromolecular secretory apparatus. Toxoplasma gondii armed with 10–12 5-6 microtubule-associated vesicles (MVs) presumably iterative discharge. Here, we have addressed the localization functional significance of intraconoidal microtubule (ICMT)-associated proteins instrumental invasion. Mechanistically, depletion ICMAP2 leads dissociation ICMTs, their...
Abstract Coenzyme A (CoA) is an essential molecule acting in metabolism, post-translational modification, and regulation of gene expression. While all organisms synthesize CoA, many, including humans, are unable to produce its precursor, pantothenate. Intriguingly, like most plants, fungi bacteria, parasites the coccidian subgroup Apicomplexa, human pathogen Toxoplasma gondii , possess enzymes required for de novo synthesis Here, importance CoA pantothenate biosynthesis acute chronic stages...
Summary The intracellular parasite T oxoplasma gondii converts from a rapidly replicating tachyzoite form during acute infection to quiescent encysted bradyzoite stage that persists inside long‐lived cells chronic infection. Bradyzoites adopt reduced metabolism and slow replication while waiting for an opportunity recrudesce the within host. Interconversion between these two developmental stages is characterized by expression of glycolytic isoenzymes play key roles in metabolism. genome...
Abstract Toxoplasma gondii infects a broad range of hosts and can establish chronic infections with the formation brain cysts. Infected animals show altered risk behaviour which has been suggested to increase capture probability hosts, thus enhance parasite transmission. It proposed that ability cysts secrete tyrosine hydroxylase could mediate these behavioural alterations. We tested involvement secreted hydroxylase, coded by AaaH2 gene, in development alterations mouse behaviour, generating...
Abstract Active host cell invasion by the obligate intracellular apicomplexan parasites relies on formation of a moving junction, which connects parasite and plasma membranes during entry. Invading Toxoplasma gondii tachyzoites secrete their rhoptry content insert complex RON proteins cytoplasmic side membrane providing an anchor to tethers. Here we show that rhoptry-resident kinase RON13 is key virulence factor plays crucial role in Cryo-EM, assays, phosphoproteomics cellular analyses...
Toxoplasma gondii is an intracellular apicomplexan parasite that relies on cyclic GMP (cGMP)-dependent signaling to trigger timely egress from host cells in response extrinsic and intrinsic signals. A guanylate cyclase (GC) complex, conserved across the Apicomplexa, plays a pivotal role integrating these signals, such as key lipid mediator phosphatidic acid changes pH ionic composition. This complex composed of atypical GC fused flippase-like P4-ATPase domain assembled with cell division...
Individuals chronically infected with the intracellular parasite Toxoplasma gondii are at risk of experiencing reactivated disease that can result in progressive loss vision. No effective treatments exist for chronic toxoplasmosis due part to a poor understanding biology underlying infection and lack well-validated potential targets. We show here T. transporter is functionally linked protein digestion within lysosome-like organelle this necessary sustain culture experimentally mice. Ablating...
The Apicomplexa phylum comprises diverse parasitic organisms that have evolved from a free-living ancestor. These obligate intracellular parasites exhibit versatile metabolic capabilities reflecting their capacity to survive and grow in different hosts varying niches. Determined by nutrient availability, they either use biosynthesis machineries or largely depend on host for metabolite acquisition. Because vitamins cannot be synthesized the mammalian host, enzymes required synthesis...
To gain access to the intracellular cytoplasmic niche essential for their growth and replication, apicomplexan parasites such as Toxoplasma gondii rely on timely secretion of two types apical organelles named micronemes rhoptries. Rhoptry proteins are key host cell invasion remodeling, however, molecular mechanisms underlying tight control rhoptry discharge poorly understood. Here, we report identification functional characterization novel T. thrombospondin-related implicated in exocytosis....
Abstract Virulence and persistence of the obligate intracellular parasite Toxoplasma gondii involve secretion effector proteins belonging to family dense granule (GRAs) that act notably as modulators host defense mechanisms participate in cyst wall formation. The subset GRAs residing parasitophorous vacuole (PV) or exported into cell, undergo proteolytic cleavage Golgi upon action aspartyl protease 5 (ASP5). In tachyzoites, ASP5 substrates play central roles morphology PV export effectors...
Apicomplexan parasites are responsible for devastating diseases, including malaria, toxoplasmosis, and cryptosporidiosis. Current treatments limited by emerging resistance to, as well the high cost toxicity of existing drugs. As obligate intracellular parasites, apicomplexans rely on uptake many essential metabolites from their host. Toxoplasma gondii, causative agent is auxotrophic several metabolites, sugars (e.g., myo-inositol), amino acids tyrosine), lipidic compounds lipid precursors...
It is estimated that more than 2 billion people are chronically infected with the intracellular protozoan parasite Toxoplasma gondii (T. gondii). Despite this, there currently no vaccine to prevent infection in humans, and recognized curative treatment clear tissue cysts. A major hurdle for identifying effective drug candidates against chronic-stage cysts has been low throughput of existing vitro assays testing survival bradyzoites. We have developed a luciferase-based platform specifically...
Introduction:The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signaling pathway plays a fundamental role in modulating diverse physiological processes within the central nervous system (CNS) including blood flow, inflammation, neuroprotection, neuronal signaling, and metabolism.sGC stimulators are small-molecule agonists of sGC that synergize with enhance endogenous NO signaling.As such, may provide therapeutic benefits diseases impaired signaling.Many neurodegenerative have...
ABSTRACT To gain access to the intracellular cytoplasmic niche essential for their growth and replication, apicomplexan parasites such as Toxoplasma gondii rely on timely secretion of two types apical organelles named micronemes rhoptries. Rhoptry proteins are key host cell invasion remodelling, however, molecular mechanisms underlying thight control rhoptry discharge poorly understood. Here, we report identification functional characterization novel T. thrombospondin-related implicated in...
Toxoplasma gondii is a pervasive apicomplexan parasite that can cause severe disease and death in immunocompromised individuals the developing foetus. The treatment of toxoplasmosis often leads to serious side effects novel drugs drug targets are therefore actively sought. In 2014, Mageed colleagues suggested T. pantothenate synthetase, enzyme responsible for synthesis vitamin B5 (pantothenate), precursor important cofactor, coenzyme A, good target. Their conclusion was based on ability...