Affinage · Toxoplasma gondii

GRA1

dense granule protein GRA1 · UniProt S8GIU2

Annotated
2026-09-08
100 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRA1 is a calcium-binding dense granule protein of Toxoplasma gondii that is secreted into the parasitophorous vacuole (PV) as a key structural determinant of the intravacuolar network (IVN) and host-nutrient scavenging (PMID:2798425, PMID:40576341). After host-cell invasion it is discharged from dense granules into the PV lumen as a soluble protein, with secretion delayed relative to micronemal and rhoptry proteins and peaking around 20 min post-invasion, and it subsequently associates peripherally with the tubulo-vesicular IVN — distinct from the integral IVN membrane protein GRA2 (PMID:9208224, PMID:7615684). Its central mechanistic role is maintaining IVN structural integrity: conditional depletion in tachyzoites disrupts IVN membrane tubules, mislocalizes other GRA effectors (including GRA17) away from the PV membrane, collapses glucose and pantothenate uptake, impairs glycolytic and TCA metabolism and ATP levels, damages the mitochondrion and apicoplast, and arrests growth while driving bradyzoite differentiation (PMID:40576341). GRA1 expression and trafficking are stage-specific — abundant in tachyzoites and bradyzoites but not exocytosed in sporozoites and absent from enteric merozoite stages — and during cyst formation it redistributes to establish a continuous matrix in the cyst interior and inner cyst wall (PMID:9353039, PMID:10072322, PMID:31619500). Calcium binding was inferred from 45Ca2+ labeling and sequence features (PMID:2798425), and transcription depends on repeated A/TGAGACG cis-elements in the GRA1 promoter (PMID:8858595). Beyond its intravacuolar function, recombinant GRA1 induces apoptosis of human monocytes through an autocrine TGF-β mechanism (PMID:21390541).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1989 Medium

    Establishing GRA1's identity answered where this abundant antigen resides and what biochemical property it carries, defining it as a secreted calcium-binding dense granule protein.

    Evidence Immunocytochemistry, 45Ca2+ radiolabeling, and cloning/heterologous expression of GRA1 (P23/P24)

    PMID:2798425

    Open questions at the time
    • Ca2+ binding inferred from labeling and homology, not enzymatically reconstituted
    • No defined EF-hand or structural basis for Ca2+ coordination
    • Functional consequence of Ca2+ binding in the PV not addressed
  2. 1993 Medium

    Comparative immunogold localization resolved that GRA proteins are differentially sorted, placing GRA1 in the soluble vacuolar/cyst matrix rather than membranes or cyst wall.

    Evidence Colloidal immunogold immunoelectron microscopy of tachyzoites and bradyzoites

    PMID:8344403

    Open questions at the time
    • Sorting mechanism directing GRA1 to matrix vs. membrane unknown
    • No functional test of matrix localization
  3. 1995 High

    Reciprocal immunolabeling and fractionation distinguished GRA1's peripheral IVN association from GRA2's integral membrane insertion, defining how GRA1 engages the intravacuolar network.

    Evidence IFA, immunoEM, and cell fractionation of infected host cells comparing GRA1 and GRA2

    PMID:7615684

    Open questions at the time
    • Molecular basis of GRA1 peripheral membrane association not defined
    • No demonstration of direct lipid or protein binding to IVN
  4. 1996 High

    Promoter dissection identified the cis-elements driving GRA1 transcription, defining how its high-level expression is regulated.

    Evidence Transient CAT reporter transfection with promoter deletion and mutation analysis

    PMID:8858595

    Open questions at the time
    • Trans-acting factors binding the A/TGAGACG motifs not identified
    • Link to stage-specific expression not established
  5. 1997 Medium

    Secretion-kinetics and stage-comparison studies established that GRA1 discharge is temporally distinct (post-invasion) and stage-regulated, being retained in sporozoites rather than secreted into the first PV.

    Evidence Quantitative immunoassay/IFA/IEM of invasion kinetics; immunolabeling of sporozoite versus tachyzoite invasion

    PMID:9208224 PMID:9353039

    Open questions at the time
    • Signal triggering delayed dense-granule secretion unknown
    • Mechanism of sporozoite-specific retention unresolved
  6. 1999 Medium

    In vivo staining across enteric stages showed GRA1 is absent from merozoites and coccidian stages, refining the stage-specificity of its expression.

    Evidence Immunolight and electron microscopy of cat intestinal sections

    PMID:10072322

    Open questions at the time
    • Basis of stage-specific transcriptional silencing not defined
    • Independence from NTPase not mechanistically explained
  7. 2006 Medium

    Analysis of MIC5-knockout parasites revealed that GRA1 undergoes regulated proteolytic processing controlled by the MIC5/MPP2 axis, connecting dense-granule and micronemal protein maturation.

    Evidence MIC5 KO with genetic complementation, GRA1 Western blot, and ALLN protease inhibition

    PMID:16980407

    Open questions at the time
    • Direct protease acting on GRA1 not identified
    • Functional consequence of GRA1 processing unknown
  8. 2008 Medium

    Co-localization studies placed GRA1 within early post-invasion host-cytosolic strands containing GRA3 and GRA7, hinting at coordination between dense-granule and rhoptry protein networks.

    Evidence IFA co-localization of GRA7 with GRA1, GRA3, ROP2, ROP4 in infected cells

    PMID:18809661

    Open questions at the time
    • Co-localization by IFA only, no direct interaction shown for GRA1
    • Functional role of GRA1 in these strands not tested
  9. 2011 Medium

    A host-directed assay showed recombinant GRA1 can drive human monocyte apoptosis via autocrine TGF-β signaling, indicating an immunomodulatory activity distinct from its intravacuolar structural role.

    Evidence Monocyte apoptosis assays with recombinant GRA1, TGF-β receptor inhibition, and neutralizing antibodies

    PMID:21390541

    Open questions at the time
    • Physiological relevance of secreted native GRA1 in this pathway unclear
    • GRA1 receptor/target on monocytes not identified
  10. 2016 Medium

    Systematic knockout attempts across the GRA1–9 loci found GRA1 refractory to deletion in the RH strain, implicating it as essential in contrast to the dispensable GRA2–9.

    Evidence Homologous-recombination gene targeting in T. gondii RH strain

    PMID:27458822

    Open questions at the time
    • Negative result does not formally prove essentiality
    • No conditional system used to define the essential function here
  11. 2018 Medium

    Proximity-labeling mapping used GRA1 as a bait to enumerate the PV proteome, defining its molecular neighborhood and identifying novel dense granule proteins.

    Evidence BioID (GRA1-BirA*) and APEX (GRA1-APEX) proximity labeling with mass spectrometry and IFA validation

    PMID:30362762

    Open questions at the time
    • Proximity does not establish direct GRA1 binding
    • Which neighbors are functional partners not determined
  12. 2019 Medium

    Time-resolved imaging during in vitro cyst formation showed GRA1 dynamically relocalizes to build a continuous cyst-interior matrix and inner cyst wall, extending its structural role into the bradyzoite stage.

    Evidence IFA of GRA1 with cyst-wall markers over differentiation time course; genetic deletion of other GRAs

    PMID:31619500

    Open questions at the time
    • GRA1 KO not achievable, so its functional requirement for cyst matrix untested
    • Signals directing GRA1 relocalization unknown
  13. 2025 High

    Conditional depletion finally resolved GRA1's essential mechanism, showing it maintains IVN integrity required for GRA effector secretion, host-nutrient scavenging, metabolic homeostasis, and organelle integrity.

    Evidence Conditional degron depletion of GRA1 with metabolomics, organelle imaging, GRA localization, nutrient uptake, and differentiation assays

    PMID:40576341

    Open questions at the time
    • Direct molecular basis of GRA1-IVN membrane interaction not defined
    • Whether metabolic defects are all downstream of IVN disruption vs. independent roles not separated
  14. 2025 Medium

    Detection of GRA1 in infected-neuron extracellular vesicles that reprogram astrocytes raised the possibility of a GRA1 role in host CNS signaling beyond the PV.

    Evidence EV proteomics, TEM/NTA, and astrocyte gene-expression assays from infected primary neurons

    PMID:40523037

    Open questions at the time
    • GRA1's individual contribution to EV-driven astrocyte effects not dissected
    • Mechanism of GRA1 loading into EVs unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct molecular basis of GRA1's peripheral association with IVN membranes and how its calcium-binding activity contributes to IVN integrity and nutrient scavenging remain unresolved.
  • No structural model of GRA1 or its membrane/Ca2+-binding interface
  • Whether Ca2+ binding is required for IVN function untested
  • Direct binding partners on the IVN not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
46 PV PROTEINS IDENTIFIED BY GRA1 PROXIMITY LABELING, INCL. 20 KNOWN GRAS [#10]GRA17 AND OTHER GRA EFFECTORS (SECRETION DEPENDENT ON GRA1) [#14]GRA2 (DISTINCT IVN ASSOCIATION; CO-LOCALIZED) [#2]GRA3, GRA7 (POST-INVASION HOST-CYTOSOLIC STRANDS, CO-LOCALIZATION) [#7]MIC5/MPP2 (REGULATES GRA1 PROTEOLYTIC PROCESSING) [#12]

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 GRA1 is secreted from dense granules into the parasitophorous vacuole (PV) lumen as a soluble protein after host cell invasion, with secretion delayed until after the parasite is fully within the PV (peaking at ~20 min post-invasion), distinct from the earlier secretion of micronemal and rhoptry proteins. Immunofluorescence, immunoelectron microscopy, and quantitative immunoassays comparing kinetics of secretion from micronemes, rhoptries, and dense granules during host cell invasion European journal of cell biology High 9208224
1989 GRA1 (P23/P24) is a calcium-binding dense granule protein that is secreted into the host-cell-modified phagosome (parasitophorous vacuole) in both tachyzoite and bradyzoite forms; 45Ca2+ labeling and regional sequence homologies indicate Ca2+-binding properties. Immunocytochemical localization, 45Ca2+ radiolabeling, gene cloning and sequencing, heterologous expression in E. coli and eukaryotic cells Proceedings of the National Academy of Sciences of the United States of America Medium 2798425
1995 Following host-cell invasion, GRA1 is secreted from dense granules into the PV lumen as a soluble protein; it subsequently becomes peripherally associated with the intravacuolar tubulo-vesicular network (IVN). GRA1 is distinct from GRA2, which is delivered within multi-lamellar vesicles and becomes an integral membrane component of the IVN. Immunolabeling (IFA and immunoelectron microscopy) and cell fractionation of infected host cells Journal of cell science High 7615684
1996 The GRA1 promoter contains critical cis-acting elements, specifically repeated motifs (A/TGAGACG) located between -129 and -47 relative to the transcription start site, that are required for optimal promoter activity; mutation of these motifs reduces CAT reporter expression. Transient transfection of T. gondii with CAT reporter gene constructs, promoter deletion analysis, quantitative CAT assay, mutation analysis Molecular microbiology High 8858595
1993 GRA1 is localized to the matrix of dense granules in both tachyzoites and bradyzoites and is secreted into the parasitophorous vacuole and cyst ground substance. In bradyzoites, selective sorting of dense granule contents occurs: GRA2 is preferentially associated with the cyst wall ground substance and tubular network elements, GRA5 is on the delimiting membrane, while GRA1 distributes to the vacuolar/cyst matrix, indicating differential targeting of GRA proteins. Colloidal immunogold labeling with monoclonal antibodies, immunoelectron microscopy on tachyzoites and bradyzoites from distinct strains Experimental parasitology Medium 8344403
1997 Sporozoites contain GRA1 protein within cytoplasmic dense granules but do not exocytose GRA1 during formation of the first parasitophorous vacuole (PV1); GRA1 is retained intracellularly rather than being secreted into PV1, unlike in tachyzoite invasion. Immunolabeling of oocyst-derived sporozoites and infected host cells at defined time points post-infection, comparison with tachyzoite secretion Infection and immunity Medium 9353039
1999 GRA1 protein is absent from the dense granules and parasitophorous vacuoles of merozoites and enteric (coccidian) stages in the cat small intestine, in contrast to its strong expression and secretion in tachyzoites and bradyzoites; this stage-specific absence is independent of NTPase expression. Immunolight and electron microscopy with antibodies against GRA1–6 and NTPase on cat intestinal sections containing merozoites, asexual and sexual stages Experimental parasitology Medium 10072322
2008 Within 10 min of invasion, GRA7 localizes to strand-like structures in the host cytosol that also contain GRA1 and GRA3, and GRA7 forms an association with rhoptry proteins ROP2 and ROP4 in infected host cells; this represents the first reported interaction between rhoptry-secreted and dense granule-secreted proteins. Immunofluorescence localization of GRA7 in infected host cells, co-localization with GRA1, GRA3, ROP2, and ROP4; phosphorylation analysis Infection and immunity Medium 18809661
2016 Targeted knockout of the GRA1 locus in virulent type I RH strain could not be obtained, suggesting GRA1 may be essential for parasite viability, in contrast to GRA2–9 which were successfully knocked out. Targeted gene knockout attempts using homologous recombination in T. gondii RH strain; successful knockouts at GRA2–9 loci but not GRA1 or GRA10 PloS one Medium 27458822
2019 During tachyzoite-to-bradyzoite differentiation (in vitro cyst development), GRA1 relocalizes dynamically: by day 1 post-differentiation it is at the cyst periphery (colocalized with Dolichos biflorus agglutinin stain); by day 2, after GRA2 moves to the periphery, GRA1 establishes a continuous matrix pattern in the cyst interior; ultimately GRA1 is found predominantly in the inner layers of the cyst wall. Immunofluorescence localization of GRA1, GRA2, GRA4, GRA6, GRA9, GRA12 with cyst wall markers at multiple time points during in vitro differentiation; genetic deletion of individual GRA proteins to assess effects on cyst matrix and wall accumulation mSphere Medium 31619500
2018 Using GRA1 as bait in proximity-based biotinylation (BioID with GRA1-BirA* and APEX with GRA1-APEX), 46 proteins were identified in proximity to GRA1 in the parasitophorous vacuole, of which 20 were known GRA proteins; 5 of 26 novel proteins were validated as bona fide dense granule proteins by localization studies. Two proximity-based protein labeling approaches (BioID/BirA* and APEX) using GRA1 as bait, followed by streptavidin pulldown and mass spectrometry; localization validation by IFA Journal of proteome research Medium 30362762
2011 Recombinant GRA1 protein (but not MIC3) induces apoptosis of human monocytes via an autocrine TGF-β signaling mechanism: GRA1 stimulation activates TGF-β transcription and expression in monocytes, and selective inhibition of TGF-β type I receptors or neutralization of TGF-β reverses GRA1-induced apoptosis. Treatment of monocytes from patients with congenital toxoplasmosis and healthy donors with recombinant GRA1; apoptosis assays; TGF-β receptor inhibition; TGF-β neutralizing antibodies; RT-PCR for TGF-β and iNOS Apoptosis : an international journal on programmed cell death Medium 21390541
2006 Proteolysis of GRA1 is enhanced in MIC5 knockout parasites, indicating that MIC5 (or its downstream effector MPP2) influences proteolytic processing of GRA1 in addition to micronemal proteins; this phenotype is reversed by ALLN protease inhibitor treatment. MIC5 gene knockout by homologous recombination, Western blot analysis of GRA1 processing in knockout vs. wild-type and complemented parasites, protease inhibitor treatment Eukaryotic cell Medium 16980407
2020 GRA1 (N-terminal region amino acids 41-152 of GRA6 was active, not GRA1) — specifically, recombinant GRA1 protein does NOT stimulate IFN-γ production by microglia in vitro, in contrast to the N-terminal region of GRA6. In vitro stimulation of microglia cell line and primary microglia with recombinant GRA1, GRA2, GRA5Nt, and GRA6 fragments; IFN-γ measurement by ELISA Microbes and infection Medium 31972245
2025 GRA1 plays a critical role in maintaining the structural integrity of the intravacuolar network (IVN) within the parasitophorous vacuole. Conditional depletion of GRA1 causes: (1) growth arrest of tachyzoites; (2) metabolic defects (reduced glycolysis, TCA cycle activity, and cellular ATP); (3) disruption of mitochondrion and apicoplast integrity; (4) altered IVN membrane tubule structure; (5) impaired secretion of other GRA proteins (including GRA17) to the PV membrane and host cells; (6) severely reduced uptake of host nutrients (glucose, pantothenate); and (7) increased differentiation into bradyzoites. Conditional gene depletion (auxin-inducible degron or analogous system) of GRA1 in tachyzoites; metabolomics (glycolysis, TCA activity, ATP measurement); organelle morphology by microscopy; GRA protein localization by IFA; nutrient uptake assays; bradyzoite differentiation assays mBio High 40576341
2010 Expression of GRA1 targeted to the endoplasmic reticulum (ER) in macrophages (RAW264.7) promotes cell growth and adherence, and modulates arachidonic acid-stimulated intracellular calcium release kinetics (delay in Ca2+ peak from ~3 s to ~18 s), consistent with a Ca2+-buffering or regulatory role for GRA1 in the ER. Stable transfection of RAW264.7 macrophages with pCMV/myc/ER-GRA1; indirect immunofluorescence for ER localization; growth and adherence assays; confocal calcium imaging with Fluo-3 AM Experimental parasitology Low 20122928
2025 GRA1 protein is present in extracellular vesicles (EVs) isolated from Toxoplasma-infected primary neurons, along with GRA2, GRA7, MAG1, and MAG2; these parasite-containing EVs alter astrocyte gene expression, promoting pro-inflammatory transcriptional signatures and downregulating the glutamate transporter GLT-1. EV isolation from infected primary murine cortical neurons; LC-MS/MS proteomics; nanoparticle tracking analysis; TEM; Western blot; microRNA sequencing; incubation of EVs with primary astrocytes; gene expression analysis PLoS pathogens Medium 40523037

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. European journal of cell biology 565 9208224
1989 Molecular characterization of a 23-kilodalton major antigen secreted by Toxoplasma gondii. Proceedings of the National Academy of Sciences of the United States of America 175 2798425
1995 Regulated secretion of multi-lamellar vesicles leads to formation of a tubulo-vesicular network in host-cell vacuoles occupied by Toxoplasma gondii. Journal of cell science 170 7615684
2000 Recombinant antigens to detect Toxoplasma gondii-specific immunoglobulin G and immunoglobulin M in human sera by enzyme immunoassay. Journal of clinical microbiology 132 10699010
2002 Toxoplasma gondii asexual development: identification of developmentally regulated genes and distinct patterns of gene expression. Eukaryotic cell 131 12455982
2000 DNA vaccination with genes encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2 induces partially protective immunity against lethal challenge in mice. Infection and immunity 129 10603366
2004 Use of molecular and ultrastructural markers to evaluate stage conversion of Toxoplasma gondii in both the intermediate and definitive host. International journal for parasitology 118 15003495
2004 Usefulness of Toxoplasma gondii-specific recombinant antigens in serodiagnosis of human toxoplasmosis. Journal of clinical microbiology 98 15071048
2003 Generation of Toxoplasma gondii GRA1 protein and DNA vaccine loaded chitosan particles: preparation, characterization, and preliminary in vivo studies. International journal of pharmaceutics 83 14559390
1995 Stable DNA transformation of Toxoplasma gondii using phleomycin selection. Gene 82 8522178
2008 The Toxoplasma gondii dense granule protein GRA7 is phosphorylated upon invasion and forms an unexpected association with the rhoptry proteins ROP2 and ROP4. Infection and immunity 78 18809661
2007 An enhanced GRA1-GRA7 cocktail DNA vaccine primes anti-Toxoplasma immune responses in pigs. Vaccine 63 18221825
2003 A GRA1 DNA vaccine primes cytolytic CD8(+) T cells to control acute Toxoplasma gondii infection. Infection and immunity 60 12496180
2007 GRA7 provides protective immunity in cocktail DNA vaccines against Toxoplasma gondii. Parasite immunology 58 17727568
2010 Evaluation of immune responses in sheep induced by DNA immunization with genes encoding GRA1, GRA4, GRA6 and GRA7 antigens of Toxoplasma gondii. Veterinary parasitology 57 21251760
2003 Molecular dissection of the human B-cell response against Toxoplasma gondii infection by lambda display of cDNA libraries. International journal for parasitology 54 12633654
1997 Toxoplasma gondii sporozoites form a transient parasitophorous vacuole that is impermeable and contains only a subset of dense-granule proteins. Infection and immunity 51 9353039
2003 Characterisation of Toxoplasma gondii engineered to express mouse interferon-gamma. International journal for parasitology 50 14572515
2006 Usefulness of Toxoplasma gondii recombinant antigens (GRA1, GRA7 and SAG1) in an immunoglobulin G avidity test for the serodiagnosis of toxoplasmosis. Parasitology research 49 16896649
2001 Identification of a human immunodominant B-cell epitope within the GRA1 antigen of Toxoplasma gondii by phage display of cDNA libraries. International journal for parasitology 48 11730793
2000 Enzyme-linked immunosorbent assays using the recombinant dense granule antigens GRA6 and GRA1 of Toxoplasma gondii for detection of immunoglobulin G antibodies. Clinical and diagnostic laboratory immunology 47 10882660
2018 Bioinformatics analysis of single and multi-hybrid epitopes of GRA-1, GRA-4, GRA-6 and GRA-7 proteins to improve DNA vaccine design against Toxoplasma gondii. Journal of parasitic diseases : official organ of the Indian Society for Parasitology 46 29844632
1999 The expression and distribution of dense granule proteins in the enteric (Coccidian) forms of Toxoplasma gondii in the small intestine of the cat. Experimental parasitology 46 10072322
1996 Common cis-acting elements critical for the expression of several genes of Toxoplasma gondii. Molecular microbiology 46 8858595
1993 Toxoplasma gondii: differential location of antigens secreted from encysted bradyzoites. Experimental parasitology 45 8344403
2006 Toxoplasma gondii: an evaluation of diagnostic value of recombinant antigens in a murine model. Experimental parasitology 44 16707125
2011 Increased survival time in mice vaccinated with a branched lysine multiple antigenic peptide containing B- and T-cell epitopes from T. gondii antigens. Vaccine 42 21939715
2003 High yield expression and single-step purification of Toxoplasma gondii SAG1, GRA1, and GRA7 antigens in Escherichia coli. Protein expression and purification 42 12509997
2012 Peptide microarray analysis of in silico-predicted epitopes for serological diagnosis of Toxoplasma gondii infection in humans. Clinical and vaccine immunology : CVI 40 22496494
2008 Toxoplasma gondii: enzyme-linked immunosorbent assay using different fragments of recombinant microneme protein 1 (MIC1) for detection of immunoglobulin G antibodies. Experimental parasitology 40 18207143
2009 Evaluation of protective effect of multi-epitope DNA vaccine encoding six antigen segments of Toxoplasma gondii in mice. Parasitology research 39 19288132
2019 A systematic review on the role of GRA proteins of Toxoplasma gondii in host immunization. Journal of microbiological methods 38 31442457
2010 Functional characterization of in vivo effector CD4(+) and CD8(+) T cell responses in acute Toxoplasmosis: an interplay of IFN-gamma and cytolytic T cells. Vaccine 37 20117266
1999 Immunogenicity of recombinant BCG producing the GRA1 antigen from Toxoplasma gondii. Vaccine 37 10067676
2004 Limited value of assays using detection of immunoglobulin G antibodies to the two recombinant dense granule antigens, GRA1 and GRA6 Nt of Toxoplasma gondii, for distinguishing between acute and chronic infections in pregnant women. Clinical and diagnostic laboratory immunology 35 15539499
2016 Phenotypes Associated with Knockouts of Eight Dense Granule Gene Loci (GRA2-9) in Virulent Toxoplasma gondii. PloS one 34 27458822
2015 Serodiagnosis of Toxoplasma gondii infection in farm animals (horses, swine, and sheep) by enzyme-linked immunosorbent assay using chimeric antigens. Parasitology international 33 25817245
2014 Diagnostic value of a Rec-ELISA using Toxoplasma gondii recombinant SporoSAG, BAG1, and GRA1 proteins in murine models infected orally with tissue cysts and oocysts. PloS one 33 25268351
2014 Comparative efficacy of a multi-epitope DNA vaccine via intranasal, peroral, and intramuscular delivery against lethal Toxoplasma gondii infection in mice. Parasites & vectors 33 24685150
2012 Multicomponent DNA vaccine-encoding Toxoplasma gondii GRA1 and SAG1 primes: anti-Toxoplasma immune response in mice. Parasitology research 32 22837100
1997 Expression of Toxoplasma gondii genes in the closely-related apicomplexan parasite Neospora caninum. Molecular and biochemical parasitology 31 9178265
2015 A new Toxoplasma gondii chimeric antigen containing fragments of SAG2, GRA1, and ROP1 proteins-impact of immunodominant sequences size on its diagnostic usefulness. Parasitology research 30 26055987
2019 Toxoplasma gondii Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall. mSphere 29 31619500
2013 Identification of novel B cell epitopes within Toxoplasma gondii GRA1. Experimental parasitology 28 24090568
2019 The first study on the usefulness of recombinant tetravalent chimeric proteins containing fragments of SAG2, GRA1, ROP1 and AMA1 antigens in the detection of specific anti-Toxoplasma gondii antibodies in mouse and human sera. PloS one 27 31170254
2014 Evaluation of recombinant granule antigens GRA1 and GRA7 for serodiagnosis of Toxoplasma gondii infection in dogs. BMC veterinary research 27 25016474
1999 In vivo expression and distribution of dense granule protein 7 (GRA7) in the exoenteric (tachyzoite, bradyzoite) and enteric (coccidian) forms of Toxoplasma gondii. Parasitology 26 10503251
2018 Identification of Novel Dense-Granule Proteins in Toxoplasma gondii by Two Proximity-Based Biotinylation Approaches. Journal of proteome research 25 30362762
2013 Seroprevalence of toxoplasmosis, toxocariasis and cysticercosis in a rural settlement, São Paulo State, Brazil. Pathogens and global health 25 23683335
2007 Construction of Toxoplasma gondii bradyzoite expressing the green fluorescent protein. Parasitology international 23 18006371
2006 Targeted deletion of MIC5 enhances trimming proteolysis of Toxoplasma invasion proteins. Eukaryotic cell 22 16980407
2015 Evaluation of an indirect ELISA using recombinant granule antigen GRA1, GRA7 and soluble antigens for serodiagnosis of Toxoplasma gondii infection in chickens. Research in veterinary science 21 25975627
2011 IFN-γ expression and infectivity of Toxoplasma infected tissues are associated with an antibody response against GRA7 in experimentally infected pigs. Veterinary parasitology 21 21414723
2014 The optimal mixture of Toxoplasma gondii recombinant antigens (GRA1, P22, ROP1) for diagnosis of ovine toxoplasmosis. Veterinary parasitology 20 25300561
2001 Towards the Toxoplasma gondii proteome: position of 13 parasite excretory antigens on a standardized map of two-dimensionally separated tachyzoite proteins. Parasitology research 20 11511000
2018 A novel chemiluminescent immunoassay based on original acridinium ester labels as better solution for diagnosis of human toxoplasmosis than conventional ELISA test. Diagnostic microbiology and infectious disease 17 29398460
2016 Toxoplasma gondii: Protective immunity induced by a DNA vaccine expressing GRA1 and MIC3 against toxoplasmosis in BALB/c mice. Experimental parasitology 17 27059254
2010 High diagnostic efficiency of IgM-ELISA with the use of multiple antigen peptides (MAP1) from T. gondii ESA (SAG-1, GRA-1 and GRA-7), in acute toxoplasmosis. Revista do Instituto de Medicina Tropical de Sao Paulo 17 20464125
2006 Age-dependent impairment of functional helper T cell responses to immunodominant epitopes of Toxoplasma gondii antigens in congenitally infected individuals. Microbes and infection 17 17223600
2014 Interferon-gamma expression and infectivity of Toxoplasma infected tissues in experimentally infected sheep in comparison with pigs. Veterinary parasitology 16 25499128
2007 Toxoplasma gondii: chimeric Dr fimbriae as a recombinant vaccine against toxoplasmosis. Experimental parasitology 14 17825290
2011 Toxoplasma gondii Dense Granule Antigen 1 stimulates apoptosis of monocytes through autocrine TGF-β signaling. Apoptosis : an international journal on programmed cell death 13 21390541
2019 Prevalence of Toxoplasma gondii parasite in captive Mexican jaguars determined by recombinant surface antigens (SAG1) and dense granular antigens (GRA1 and GRA7) in ELISA-based serodiagnosis. Experimental parasitology 12 31704144
2015 A comparative study of Toxoplasma gondii seroprevalence in mink using a modified agglutination test, a Western blot, and enzyme-linked immunosorbent assays. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 12 26199291
2010 Toxoplasma gondii: expression of GRA1 gene in endoplasmic reticulum promotes both growth and adherence and modulates intracellular calcium release in macrophages. Experimental parasitology 12 20122928
2019 Toxoplasma gondii Tetravalent Chimeric Proteins as Novel Antigens for Detection of Specific Immunoglobulin G in Sera of Small Ruminants. Animals : an open access journal from MDPI 11 31847285
2013 Establishment and application of a loop-mediated isothermal amplification method for simple, specific, sensitive and rapid detection of Toxoplasma gondii. The Journal of veterinary medical science 11 23965849
2021 Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles. PLoS neglected tropical diseases 10 33651824
2020 Engineering an efficient poly-epitope vaccine against Toxoplasma gondii infection: A computational vaccinology study. Microbial pathogenesis 10 33242641
2018 Analysis of Toxoplasma gondii clonal type-specific antibody reactions in experimentally infected turkeys and chickens. International journal for parasitology 10 29969590
2016 A novel chemiluminescent immunoassay for detection of Toxoplasma gondii IgG in human sera. Diagnostic microbiology and infectious disease 10 27298047
2023 Evaluation of long-term immunity and protection against T. gondii after immunization with multivalent recombinant chimeric T. gondii proteins. Scientific reports 9 37563166
2022 Toxoplasma gondii and Neospora caninum Infections in Stray Cats and Dogs in the Qinghai-Tibetan Plateau Area, China. Animals : an open access journal from MDPI 9 35681854
2019 The Impact of the Antigenic Composition of Chimeric Proteins on Their Immunoprotective Activity against Chronic Toxoplasmosis in Mice. Vaccines 9 31635267
2024 Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness. Parasites & vectors 8 38576040
2024 The Development of Toxoplasma gondii Recombinant Trivalent Chimeric Proteins as an Alternative to Toxoplasma Lysate Antigen (TLA) in Enzyme-Linked Immunosorbent Assay (ELISA) for the Detection of Immunoglobulin G (IgG) in Small Ruminants. International journal of molecular sciences 8 38673969
2021 Characterization and evaluation of a recombinant multiepitope peptide antigen MAG in the serological diagnosis of Toxoplasma gondii infection in pigs. Parasites & vectors 6 34404476
2020 The Immunogenic and Immunoprotective Activities of Recombinant Chimeric T. gondii Proteins Containing AMA1 Antigen Fragments. Vaccines 6 33276579
2017 Toward detection of toxoplasmosis from urine in mice using hydro-gel nanoparticles concentration and parallel reaction monitoring mass spectrometry. Nanomedicine : nanotechnology, biology, and medicine 6 29203146
2005 Toxoplasma gondii antigens GRA1 (p24) and SAG1 (p30): a comparison of their stimulatory influence on T-cell activation and cytokine expression in in vitro cultures. Pathobiology : journal of immunopathology, molecular and cellular biology 6 15860934
2023 In Silico Vaccine Design and Expression of the Multi-Component Protein Candidate against the Toxoplasma gondii Parasite from MIC13, GRA1, and SAG1 Antigens. Iranian journal of parasitology 5 37886246
2017 Preliminary multiplex microarray IgG immunoassay for the diagnosis of toxoplasmosis and rubella. Memorias do Instituto Oswaldo Cruz 5 28591403
2025 Design and immunological evaluation of a multi-epitope vaccine candidate against Toxoplasma gondii incorporating MIC13, GRA1, and SAG1 antigens in BALB/c mice. Food and waterborne parasitology 4 40546389
2024 Molecular Models of Toxoplasma gondii in Humans and Animals. Turkiye parazitolojii dergisi 4 38958491
2023 An In house ELISA using recombinant GRA1 and BAG1 proteins as antigen successfully detected Toxoplasma gondii infection in a flock of sheep suffering from abortions. Research in veterinary science 4 39492179
2023 Dense granule protein 3 of Toxoplasma gondii plays a crucial role in the capability of the tissue cysts of the parasite to persist in the presence of anti-cyst CD8+ T cells during the chronic stage of infection. Frontiers in immunology 4 37868957
2020 The amino-terminal region of dense granule protein 6 of Toxoplasma gondii stimulates IFN-γ production by microglia. Microbes and infection 4 31972245
2025 The critical role of Toxoplasma gondii GRA1 in nutrient salvage. mBio 3 40576341
2025 Toxoplasma gondii infection of neurons alters the production and content of extracellular vesicles directing astrocyte phenotype and contributing to the loss of GLT-1 in the infected brain. PLoS pathogens 3 40523037
2025 A Structural In Silico Analysis of Novel Epitopes from Toxoplasma gondii Proteins for the Serodiagnosis of Toxoplasmosis. International journal of molecular sciences 2 40429830
2023 A preliminary study to develop a lateral flow assay using recombinant GRA1 protein for the diagnosis of toxoplasmosis in stray cats. Comparative immunology, microbiology and infectious diseases 2 37647822
2009 Expression of the tandem enhanced yellow fluorescent marker gene in Toxoplasma gondii. Parasitology research 2 19424723
2025 In vitro expression and seroreactivity of Toxoplasma gondii GRA1 protein encoded by unmodified and nucleoside-modified mRNA constructs. Gene 1 41412557
2026 Development and validation of a gra1-bag1 RT-qPCR assay as an alternative to the mouse bioassay for assessing Toxoplasma gondii viability. Scientific reports 0 41865077
2026 Immunogenicity of a Recombinant Multi-Epitope Vaccine Incorporating GRA14, SAG1, and GRA1 Antigens of Toxoplasma gondii in BALB/c Mice. Vaccines 0 42347666
2026 Seroprevalence of IgG Antibodies Against Toxoplasma gondii in HIV-Infected and Non-Infected Population in Iquitos, Peru. Pathogens (Basel, Switzerland) 0 42075701
2026 Establishment of an ELISA for detecting oocyst-derived Toxoplasma gondii infections in sheep. Frontiers in veterinary science 0 41624283
2025 Prevalence of porcine toxoplasmosis using ERP-iELISA in Hubei Province. Parasitology research 0 41398086
2020 The effect of edelfosine on GRA1 and MIC3 expressions in acute toxoplasmosis. Parasitology research 0 31970471
2012 Optimized expression of dual reporter genes in transient transfection of purified Toxoplasma gondii using different promoters. Canadian journal of microbiology 0 22455755