scholarly journals Antigenic properties of dense granule antigen 12 protein using bioinformatics tools in order to improve vaccine design against Toxoplasma gondii

2020 ◽  
Vol 9 (2) ◽  
pp. 81
Author(s):  
Ali Dalir Ghaffari ◽  
Abdolhossein Dalimi ◽  
Fatemeh Ghaffarifar ◽  
Majid Pirestani
Keyword(s):  
Toxoplasma Gondii ◽  
Vaccine Design ◽  
Dense Granule ◽  
Bioinformatics Tools ◽  
Antigenic Properties

Toxoplasma gondii: Biochemical and biophysical characterization of recombinant soluble dense granule proteins GRA2 and GRA6

2015 ◽  
Vol 459 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Amina Bittame ◽  
Grégory Effantin ◽  
Graciane Pètre ◽  
Pauline Ruffiot ◽  
Laetitia Travier ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Dense Granule ◽  
Biophysical Characterization ◽  
Granule Proteins

Computational probing of Toxoplasma gondii major surface antigen 1 (SAG1) for enhanced vaccine design against toxoplasmosis

2020 ◽  
Vol 147 ◽  
pp. 104386 ◽  
Author(s):  
Hamidreza Majidiani ◽  
Abdolhossein Dalimi ◽  
Fatemeh Ghaffarifar ◽  
Majid Pirestani ◽  
Ali Dalir Ghaffari
Keyword(s):  
Toxoplasma Gondii ◽  
Surface Antigen ◽  
Vaccine Design ◽  
Major Surface

scholarly journals Toxoplasma gondii Dense Granule Proteins 7, 14, and 15 Are Involved in Modification and Control of the Immune Response Mediated via NF-κB Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Fumiaki Ihara ◽  
Ragab M. Fereig ◽  
Yuu Himori ◽  
Kyohko Kameyama ◽  
Kosuke Umeda ◽  
...  
Keyword(s):  
Immune Response ◽  
Toxoplasma Gondii ◽  
Dense Granule ◽  
Granule Proteins ◽  
And Control

scholarly journals RHΔgra17Δnpt1 Strain of Toxoplasma gondii Elicits Protective Immunity Against Acute, Chronic and Congenital Toxoplasmosis in Mice

2020 ◽  
Vol 8 (3) ◽  
pp. 352 ◽  
Author(s):  
Qin-Li Liang ◽  
Li-Xiu Sun ◽  
Hany M. Elsheikha ◽  
Xue-Zhen Cao ◽  
Lan-Bi Nie ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Cellular Response ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Dense Granule ◽  
Lethal Challenge ◽  
Double Deletion ◽  
Brain Cysts

In the present study, a dense granule protein 17 (gra17) and novel putative transporter (npt1) double deletion mutant of Toxoplasma gondii RH strain was engineered. The protective efficacy of vaccination using RHΔgra17Δnpt1 tachyzoites against acute, chronic, and congenital toxoplasmosis was studied in a mouse model. Immunization using RHΔgra17Δnpt1 induced a strong humoral and cellular response, as indicated by the increased levels of anti-T. gondii specific IgG, interleukin 2 (IL-2), IL-10, IL-12, and interferon-gamma (IFN-γ). Vaccinated mice were protected against a lethal challenge dose (103 tachyzoites) of wild-type homologous (RH) strain and heterologous (PYS and TgC7) strains, as well as against 100 tissue cysts or oocysts of Pru strain. Vaccination also conferred protection against chronic infection with 10 tissue cysts or oocysts of Pru strain, where the numbers of brain cysts in the vaccinated mice were significantly reduced compared to those detected in the control (unvaccinated + infected) mice. In addition, vaccination protected against congenital infection with 10 T. gondii Pru oocysts (administered orally on day 5 of gestation) as shown by the increased litter size, survival rate and the bodyweight of pups born to vaccinated dams compared to those born to unvaccinated + infected dams. The brain cyst burden of vaccinated dams was significantly lower than that of unvaccinated dams infected with oocysts. Our data show that T. gondii RHΔgra17Δnpt1 mutant strain can protect mice against acute, chronic, and congenital toxoplasmosis by balancing inflammatory response with immunogenicity.

scholarly journals Toxoplasma gondii GRA9 Regulates the Activation of NLRP3 Inflammasome to Exert Anti-Septic Effects in Mice

2020 ◽  
Vol 21 (22) ◽  
pp. 8437
Author(s):  
Jae-Sung Kim ◽  
Seok-Jun Mun ◽  
Euni Cho ◽  
Donggyu Kim ◽  
Wooic Son ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Nlrp3 Inflammasome ◽  
Dense Granule ◽  
E Coli ◽  
Pyrin Domain ◽  
Essential Components ◽  
Bactericidal Effects ◽  
Anti Inflammatory

Dense granule proteins (GRAs) are essential components in Toxoplasma gondii, which are suggested to be promising serodiagnostic markers in toxoplasmosis. In this study, we investigated the function of GRA9 in host response and the associated regulatory mechanism, which were unknown. We found that GRA9 interacts with NLR family pyrin domain containing 3 (NLRP3) involved in inflammation by forming the NLRP3 inflammasome. The C-terminal of GRA9 (GRA9C) is essential for GRA9–NLRP3 interaction by disrupting the NLRP3 inflammasome through blocking the binding of apoptotic speck-containing (ASC)-NLRP3. Notably, Q200 of GRA9C is essential for the interaction of NLRP3 and blocking the conjugation of ASC. Recombinant GRA9C (rGRA9C) showed an anti-inflammatory effect and the elimination of bacteria by converting M1 to M2 macrophages. In vivo, rGRA9C increased the anti-inflammatory and bactericidal effects and subsequent anti-septic activity in CLP- and E. coli- or P. aeruginosa-induced sepsis model mice by increasing M2 polarization. Taken together, our findings defined a role of T. gondii GRA9 associated with NLRP3 in host macrophages, suggesting its potential as a new candidate therapeutic agent for sepsis.

scholarly journals Coimmunoprecipitation with MYR1 Identifies Three Additional Proteins within the Toxoplasma gondii Parasitophorous Vacuole Required for Translocation of Dense Granule Effectors into Host Cells

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Alicja M. Cygan ◽  
Terence C. Theisen ◽  
Alma G. Mendoza ◽  
Nicole D. Marino ◽  
Michael W. Panas ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Protein Translocation ◽  
Affinity Purification ◽  
Parasitophorous Vacuole ◽  
Dense Granule ◽  
Effector Proteins ◽  
Host Cells ◽  
Content Type ◽  
Cyclin E1 ◽  
Infected Cells

ABSTRACT Toxoplasma gondii is a ubiquitous, intracellular protozoan that extensively modifies infected host cells through secreted effector proteins. Many such effectors must be translocated across the parasitophorous vacuole (PV), in which the parasites replicate, ultimately ending up in the host cytosol or nucleus. This translocation has previously been shown to be dependent on five parasite proteins: MYR1, MYR2, MYR3, ROP17, and ASP5. We report here the identification of several MYR1-interacting and novel PV-localized proteins via affinity purification of MYR1, including TGGT1_211460 (dubbed MYR4), TGGT1_204340 (dubbed GRA54), and TGGT1_270320 (PPM3C). Further, we show that three of the MYR1-interacting proteins, GRA44, GRA45, and MYR4, are essential for the translocation of the Toxoplasma effector protein GRA16 and for the upregulation of human c-Myc and cyclin E1 in infected cells. GRA44 and GRA45 contain ASP5 processing motifs, but like MYR1, processing at these sites appears to be nonessential for their role in protein translocation. These results expand our understanding of the mechanism of effector translocation in Toxoplasma and indicate that the process is highly complex and dependent on at least eight discrete proteins. IMPORTANCE Toxoplasma is an extremely successful intracellular parasite and important human pathogen. Upon infection of a new cell, Toxoplasma establishes a replicative vacuole and translocates parasite effectors across this vacuole to function from the host cytosol and nucleus. These effectors play a key role in parasite virulence. The work reported here newly identifies three parasite proteins that are necessary for protein translocation into the host cell. These results significantly increase our knowledge of the molecular players involved in protein translocation in Toxoplasma-infected cells and provide additional potential drug targets.

scholarly journals Dense granule trafficking in Toxoplasma gondii requires a unique class 27 myosin and actin filaments

2016 ◽  
Vol 27 (13) ◽  
pp. 2080-2089 ◽  
Author(s):  
Aoife T. Heaslip ◽  
Shane R. Nelson ◽  
David M. Warshaw
Keyword(s):  
Toxoplasma Gondii ◽  
Molecular Motors ◽  
Fluorescent Protein ◽  
Molecular Motor ◽  
Structural Similarity ◽  
Dense Granule ◽  
Lytic Cycle ◽  
Secretory Vesicles ◽  
Filamentous Actin

The survival of Toxoplasma gondii within its host cell requires protein release from secretory vesicles, called dense granules, to maintain the parasite’s intracellular replicative niche. Despite the importance of DGs, nothing is known about the mechanisms underlying their transport. In higher eukaryotes, secretory vesicles are transported to the plasma membrane by molecular motors moving on their respective cytoskeletal tracks (i.e., microtubules and actin). Because the organization of these cytoskeletal structures differs substantially in T. gondii, the molecular motor dependence of DG trafficking is far from certain. By imaging the motions of green fluorescent protein–tagged DGs in intracellular parasites with high temporal and spatial resolution, we show through a combination of molecular genetics and chemical perturbations that directed DG transport is independent of microtubules and presumably their kinesin/dynein motors. However, directed DG transport is dependent on filamentous actin and a unique class 27 myosin, TgMyoF, which has structural similarity to myosin V, the prototypical cargo transporter. Actomyosin DG transport was unexpected, since filamentous parasite actin has yet to be visualized in vivo due in part to the prevailing model that parasite actin forms short, unstable filaments. Thus our data uncover new critical roles for these essential proteins in the lytic cycle of this devastating pathogen.

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