A5050019339- Toxoplasma gondii Research Studies
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Mosquito-borne diseases and control
- Parasitic Infections and Diagnostics
- Rabies epidemiology and control
- Genomics and Phylogenetic Studies
- Venomous Animal Envenomation and Studies
- HIV Research and Treatment
- RNA and protein synthesis mechanisms
- Inflammasome and immune disorders
- Hippo pathway signaling and YAP/TAZ
- Cancer Research and Treatments
- Lipid Membrane Structure and Behavior
- Heme Oxygenase-1 and Carbon Monoxide
- Malaria Research and Control
- Autophagy in Disease and Therapy
- Immune Cell Function and Interaction
- Bacteriophages and microbial interactions
- Cancer-related gene regulation
- DNA Repair Mechanisms
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- interferon and immune responses
MRC Laboratory of Molecular Biology
2020-2024
University of Geneva
2015-2022
Université Grenoble Alpes
2019
Centre National de la Recherche Scientifique
2014-2019
Unit of Virus Host Cell Interactions
2019
Inserm
2019
Université Joseph Fourier
2014
In rodents, the decrease of felid aversion induced by Toxoplasma gondii, a phenomenon termed fatal attraction, is interpreted as an adaptive manipulation neurotropic protozoan parasite. With aim understanding how parasite induces such specific behavioral modifications, we performed multiparametric analysis T. gondii-induced changes on host behavior, physiology, and brain transcriptome well cyst load distribution. Using set complementary tests, provide strong evidence that gondii lowers...
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 The obligate intracellular parasite Toxoplasma gondii possesses a repertoire of 11 myosins. Three class XIV motors participate in motility, invasion and egress, whereas the XXII myosin F is implicated organelle positioning inheritance apicoplast. Here we provide evidence that TgUNC acts as chaperone dedicated to folding, assembly function all conditional ablation recapitulates phenome known myosins uncovers two functions basal complex constriction synchronized division within...
Micronemes and rhoptries are specialized secretory organelles that deploy their contents at the apical tip of apicomplexan parasites in a regulated manner. The proteins participate motility, invasion, egress subjected to proteolytic maturation prior organellar storage discharge. Here we establish Toxoplasma gondii aspartyl protease 3 (ASP3) resides endosomal-like compartment is crucially associated rhoptry discharge during invasion host cell plasma membrane lysis egress. A comparison...
Rhoptries are club-shaped, regulated secretory organelles that cluster at the apical pole of apicomplexan parasites. Their discharge is essential for invasion and establishment an intracellular lifestyle. Little known about rhoptry biogenesis recycling during parasite division. In Toxoplasma gondii, positioning rhoptries involves armadillo repeats only protein (ARO) myosin F (MyoF). Here, we show two ARO partners, ARO-interacting (AIP) adenylate cyclase β (ACβ) localize to a subcompartment....
Invasion and egress are two key steps in the lytic cycle of Apicomplexa that governed by sequential discharge proteins from apical secretory organelles called micronemes rhoptries. In Toxoplasma gondii, biogenesis these specialized depends on post Golgi trafficking machinery, forming an endosomal-like compartment (ELC) resembling endomembrane systems found eukaryotes. this study, we have characterized four phylogenetically related Transporter Facilitator Proteins (TFPs) conserved among...
Toxoplasma gondii infects virtually any nucleated cell and resides inside a non-phagocytic vacuole surrounded by parasitophorous vacuolar membrane (PVM). Pivotal to the restriction of T. dissemination upon infection in murine cells is recruitment immunity regulated GTPases (IRGs) guanylate binding proteins (GBPs) PVM that leads pathogen elimination. The virulent type I RH strain secretes handful effectors including dense granule protein GRA7, serine–threonine kinases ROP17 ROP18,...
In Toxoplasma gondii, as in other eukaryotes, a subset of the amino-acyl-tRNA synthetases are arranged into an abundant cytoplasmic multi-aminoacyl-tRNA synthetase (MARS) complex. Through series genetic pull-down assays, we have identified enzymes this complex as: methionyl-, glutaminyl-, glutamyl-, and tyrosyl-tRNA synthetases, show that N-terminal GST-like domain partially disordered hybrid scaffold protein, Tg-p43, is sufficient for assembly intact Our gel filtration studies revealed...
Plasmodium falciparum and Toxoplasma gondii are obligate intracellular parasites that belong to the phylum of Apicomplexa cause major human diseases. Their access an lifestyle is reliant on coordinated release proteins from specialized apical organelles called micronemes rhoptries. A specific phosphatidic acid effector, acylated pleckstrin homology domain-containing protein (APH) plays a central role in microneme exocytosis thus essential for motility, cell entry, egress. TgAPH surface...
Abstract Toxoplasmic encephalitis is an AIDS-defining condition. The decline of IFN-γ-producing CD4 + T cells in AIDS a major contributing factor reactivation quiescent Toxoplasma gondii to actively replicating stage infection. Hence, it important characterize CD4-independent mechanisms that constrain acute T. We investigated the vivo regulation IFN-γ production by CD8 cells, DN and NK response Our data show processing these non-CD4 dependent on both IL-12 IL-18 secretion bioactive requires...
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...
The evolutionary arms race between pathogens and hosts has resulted in acquiring diverse adaptive countermeasures that antagonize host immunity. Ubiquitylation of lipopolysaccharide (LPS) on cytosol-invading bacteria by the E3 ligase RNF213 creates 'eat-me' signals for antibacterial autophagy but whether how cytosol-adapted avoid LPS ubiquitylation remains poorly understood. Here we show Shigella flexneri, a professional cytosol-dwelling enterobacterium, actively antagonizes through IpaH1.4,...
The apicomplexans, including the coccidian pathogen Toxoplasma gondii, are obligate intracellular parasites whose growth and development intricately linked to metabolism of their host. T. gondii depends on its host for salvage energy sources, building blocks, vitamins cofactors survive replicate. Additionally, metabolites directly impact parasite life cycle by triggering or halting differentiation. Although infects a wide range cells, it has evolved modulate maximally exploit host's...
Typically illustrating the ‘manipulation hypothesis’, Toxoplasma gondii is widely known to trigger sustainable behavioural changes during chronic infection of intermediate hosts enhance transmission its feline definitive hosts, ensuring survival and dissemination. During stage in rodents, a variety neurological dysfunctions have been unravelled correlated with loss cat fear, among other phenotypic impacts. However, underlying alteration(s) driving these modifications only partially...
Innate immunity senses microbial ligands known as pathogen-associated molecular patterns (PAMPs). Except for nucleic acids, PAMPs are exceedingly taxa-specific, thus enabling pattern recognition receptors to detect cognate pathogens while ignoring others. How the E3 ubiquitin ligase RNF213 can respond phylogenetically distant pathogens, including Gram-negative Salmonella, Gram-positive Listeria, and eukaryotic Toxoplasma, remains unknown. Here we report that evolutionary history of is...
Abstract Toxoplasmic encephalitis is an AIDS-defining condition in HIV + individuals. The decline of IFN-γ-producing CD4 T cells AIDS a major contributing factor reactivation quiescent Toxoplasma gondii to actively replicating stage infection. Hence, it important identify CD4-independent mechanisms control acute T. Here we have investigated the targeted expansion and regulation IFN-γ production by CD8 cells, DN NK response infection using IL-2 complex (IL2C) pre-treatment vivo mouse model....