A5064992009- Toxoplasma gondii Research Studies
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Parasitic Infections and Diagnostics
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Viral Infections and Immunology Research
- Bacteriophages and microbial interactions
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
Centre National de la Recherche Scientifique
2016-2023
Institut pour l'avancée des biosciences
2018-2023
Inserm
2018-2023
Université Grenoble Alpes
2016-2023
Unit of Virus Host Cell Interactions
2021-2023
Institut de Biosciences et Biotechnologies
2018-2020
Translational Innovation in Medicine and Complexity
2019
Université Joseph Fourier
2016
Toxoplasma gondii cysts reactivate during immune deficiency and cause fatal encephalitis. Parasite molecules that coordinate the development of acute chronic infection are poorly characterized. Here, we show many intravacuolar network membrane parasitophorous vacuole membrane-associated dense granule (GRA) proteins orchestrate in vivo . A subset these GRA also modulate virulence, one protein associates with membranes, namely GRA12, was identified as a major virulence factor required for...
The Apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that include Toxoplasma gondii , Plasmodium and Cryptosporidium spp., which infect humans animals cause severe parasitic diseases. Available therapeutics against these diseases are limited by suboptimal efficacy frequent side effects, as well the emergence spread resistance. We use drug repurposing strategy identify altiratinib, compound originally developed to treat glioblastoma, promising candidate...
Toxoplasma gondii actively invades host cells and establishes a parasitophorous vacuole (PV) that accumulates many proteins secreted by the dense granules (GRA proteins). To date, at least 23 GRA have been reported, though function(s) of most these still remains unknown. We targeted gene knockouts ten loci (GRA1-10) to investigate cellular roles essentiality classical during acute infection in virulent type I RH strain. While eight genes (GRA2-9) were successfully knocked out, GRA1 GRA10 not...
Boron-containing compounds represent a promising class of molecules with proven efficacy against wide range pathogens, including apicomplexan parasites. Following lead optimization, the benzoxaborole AN13762 was identified as preclinical candidate human malaria parasite, yet molecular target remained uncertain. Here, we uncovered parasiticidal mechanisms AN13762, by combining forward genetics transcriptome sequencing and computational mutation discovery using Toxoplasma gondii relevant model...
Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) a validated druggable target but the traditional 'single target-single drug' approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) novel ATP mimetic (L95) that bind PRS simultaneously at different neighbouring sites cover all three of substrate subsites. HFG L95 act as one...
Toxoplasma gondii is an intracellular protozoan parasite widely distributed in animals and humans. Infection of host cells proliferation are essential steps pathology. The objective this study was to develop validate a novel automatic High Content Imaging (HCI) assay T. infection proliferation. We tested various fluorescent markers strategies image analysis obtain automated method providing results comparable those from gold standard assays. No significant difference observed between the...
Abstract Background Biomarker discovery remains a major challenge for predictive medicine, in particular, the context of chronic diseases. This is true widespread protozoan Toxoplasma gondii which establishes long-lasting parasitism metazoans, humans included. microbe successively unfolds distinct genetic programs that direct transition from high to low replicative potential inside host cells. As slow-replicating cell, T. bradyzoite developmental stage persists enclosed cyst compartment...
The prolyl-tRNA synthetase (PRS) is a validated drug target for febrifugine and its synthetic analog halofuginone (HFG) against multiple apicomplexan parasites including Plasmodium falciparum Toxoplasma gondii . Here, novel ATP-mimetic centered on 1-(pyridin-4-yl) pyrrolidin-2-one (PPL) scaffold has been to bind PRS kill toxoplasma parasites. PPL series exhibited potent inhibition at the cellular ( T parasites) enzymatic Tg PRS) levels compared human counterparts. Cell-based chemical...
Introductory paragraph The apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that infect humans and animals cause severe parasitic diseases. Available therapeutics against these devastating diseases are limited by suboptimal efficacy frequent side effects, as well the emergence spread resistance. Here, we use drug repurposing strategy identify altiratinib, compound originally developed to treat glioblastoma, promising candidate with broad spectrum activity...
Toxoplasmosis caused by the intracellular parasite Toxoplasma gondii, is characterized a life-long chronic infection. The an efficient neurotropic infectious agent that establishes its “safe” life forming cysts in chronically infected animals and humans. This protocol describes specific recipes method to stain brain from mice rats for further quantification using epifluorescence microscopy. provides possibility scan entire thus numerate all cysts.