Toxoplasma protein export and effector function.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
03 Jan 2024
03 Jan 2024
Historique:
received:
28
03
2022
accepted:
16
11
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
3
1
2024
Statut:
aheadofprint
Résumé
Toxoplasma gondii is a single-celled eukaryotic parasite with a considerable host range that must invade the cells of warm-blooded hosts to survive and replicate. The challenges and opportunities that such a strategy represent have been met by the evolution of effectors that are delivered into host cells, counter host defences and co-opt host cell functions for their own purposes. These effectors are delivered in two waves using distinct machinery for each. In this Review, we focus on understanding the architecture of these protein-export systems and how their protein cargo is recognized and selected. We discuss the recent findings on the role that host manipulation has in latent Toxoplasma infections. We also discuss how these recent findings compare to protein export in the related Plasmodium spp. (the causative agent of malaria) and how this can inform our understanding of host manipulation in the larger Apicomplexa phylum and its evolution.
Identifiants
pubmed: 38172621
doi: 10.1038/s41564-023-01563-z
pii: 10.1038/s41564-023-01563-z
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : GNT2012271
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : R01AI172823
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : RO1 AI129529
Organisme : Howard Hughes Medical Institute (HHMI)
ID : Gilliam Fellowship
Informations de copyright
© 2024. Springer Nature Limited.
Références
Arandjelovic, P., Doerflinger, M. & Pellegrini, M. Current and emerging therapies to combat persistent intracellular pathogens. Curr. Opin. Pharmacol. 48, 33–39 (2019).
pubmed: 31051429
doi: 10.1016/j.coph.2019.03.013
Tenter, A. M., Heckeroth, A. R. & Weiss, L. M. Toxoplasma gondii: from animals to humans. Int. J. Parasitol. 30, 1217–1258 (2000).
pubmed: 11113252
pmcid: 3109627
doi: 10.1016/S0020-7519(00)00124-7
Taylor, S. et al. A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314, 1776–1780 (2006).
pubmed: 17170305
doi: 10.1126/science.1133643
Saeij, J. P. et al. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314, 1780–1783 (2006).
pubmed: 17170306
pmcid: 2646183
doi: 10.1126/science.1133690
Saeij, J. P. et al. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445, 324–327 (2007).
pubmed: 17183270
doi: 10.1038/nature05395
Ben Chaabene, R., Lentini, G. & Soldati-Favre, D. Biogenesis and discharge of the rhoptries: key organelles for entry and hijack of host cells by the Apicomplexa. Mol. Microbiol. 115, 453–465 (2021).
pubmed: 33368727
doi: 10.1111/mmi.14674
Cova, M. M., Lamarque, M. H. & Lebrun, M. How Apicomplexa parasites secrete and build their invasion machinery. Annu. Rev. Microbiol. 76, 619–640 (2022).
pubmed: 35671531
doi: 10.1146/annurev-micro-041320-021425
Sasai, M. & Yamamoto, M. Anti-Toxoplasma host defense systems and the parasitic counterdefense mechanisms. Parasitol. Int. 89, 102593 (2022).
pubmed: 35500831
doi: 10.1016/j.parint.2022.102593
Denkers, E. Y., Bzik, D. J., Fox, B. A. & Butcher, B. A. An inside job: hacking into Janus kinase/signal transducer and activator of transcription signaling cascades by the intracellular protozoan Toxoplasma gondii. Infect. Immun. 80, 476–482 (2012).
pubmed: 22104110
pmcid: 3264314
doi: 10.1128/IAI.05974-11
Boothroyd, J. C. & Dubremetz, J. F. Kiss and spit: the dual roles of Toxoplasma rhoptries. Nat. Rev. Microbiol. 6, 79–88 (2008).
pubmed: 18059289
doi: 10.1038/nrmicro1800
Bradley, P. J. & Sibley, L. D. Rhoptries: an arsenal of secreted virulence factors. Curr. Opin. Microbiol. 10, 582–587 (2007).
pubmed: 17997128
pmcid: 2682365
doi: 10.1016/j.mib.2007.09.013
Gazzinelli, R. T., Mendonca-Neto, R., Lilue, J., Howard, J. & Sher, A. Innate resistance against Toxoplasma gondii: an evolutionary tale of mice, cats, and men. Cell Host Microbe 15, 132–138 (2014).
pubmed: 24528860
pmcid: 4006104
doi: 10.1016/j.chom.2014.01.004
Haldar, A. K. et al. Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins. Proc. Natl Acad. Sci. USA 112, E5628–E5637 (2015).
pubmed: 26417105
pmcid: 4611635
doi: 10.1073/pnas.1515966112
Haldar, A. K. et al. IRG and GBP host resistance factors target aberrant, ‘non-self’ vacuoles characterized by the missing of ‘self’ IRGM proteins. PLoS Pathog. 9, e1003414 (2013).
pubmed: 23785284
pmcid: 3681737
doi: 10.1371/journal.ppat.1003414
Virreira Winter, S. et al. Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS ONE 6, e24434 (2011).
pubmed: 21931713
pmcid: 3169597
doi: 10.1371/journal.pone.0024434
Khaminets, A. et al. Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole. Cell Microbiol. 12, 939–961 (2010).
pubmed: 20109161
pmcid: 2901525
doi: 10.1111/j.1462-5822.2010.01443.x
Fentress, S. J. et al. Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence. Cell Host Microbe 8, 484–495 (2010).
pubmed: 21147463
pmcid: 3013631
doi: 10.1016/j.chom.2010.11.005
Steinfeldt, T. et al. Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent Toxoplasma gondii. PLoS Biol. 8, e1000576 (2010).
pubmed: 21203588
pmcid: 3006384
doi: 10.1371/journal.pbio.1000576
Niedelman, W. et al. The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response. PLoS Pathog. 8, e1002784 (2012).
pubmed: 22761577
pmcid: 3386190
doi: 10.1371/journal.ppat.1002784
Reese, M. L., Shah, N. & Boothroyd, J. C. The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity-related GTPases. J. Biol. Chem. 289, 27849–27858 (2014).
pubmed: 25118287
pmcid: 4183819
doi: 10.1074/jbc.M114.567057
Fleckenstein, M. C. et al. A Toxoplasma gondii pseudokinase inhibits host IRG resistance proteins. PLoS Biol. 10, e1001358 (2012).
pubmed: 22802726
pmcid: 3393671
doi: 10.1371/journal.pbio.1001358
Behnke, M. S. et al. The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18. PLoS Pathog. 8, e1002992 (2012).
pubmed: 23144612
pmcid: 3493473
doi: 10.1371/journal.ppat.1002992
Etheridge, R. D. et al. The Toxoplasma pseudokinase ROP5 forms complexes with ROP18 and ROP17 kinases that synergize to control acute virulence in mice. Cell Host Microbe 15, 537–550 (2014).
pubmed: 24832449
pmcid: 4086214
doi: 10.1016/j.chom.2014.04.002
Yamamoto, M. et al. A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3. J. Exp. Med. 206, 2747–2760 (2009).
pubmed: 19901082
pmcid: 2806617
doi: 10.1084/jem.20091703
Ong, Y. C., Reese, M. L. & Boothroyd, J. C. Toxoplasma rhoptry protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6. J. Biol. Chem. 285, 28731–28740 (2010).
pubmed: 20624917
pmcid: 2937901
doi: 10.1074/jbc.M110.112359
Boyle, J. P., Saeij, J. P., Harada, S. Y., Ajioka, J. W. & Boothroyd, J. C. Expression quantitative trait locus mapping of Toxoplasma genes reveals multiple mechanisms for strain-specific differences in gene expression. Eukaryot. Cell 7, 1403–1414 (2008).
pubmed: 18552283
pmcid: 2519772
doi: 10.1128/EC.00073-08
Jensen, K. D. et al. Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. Cell Host Microbe 9, 472–483 (2011).
pubmed: 21669396
pmcid: 3131154
doi: 10.1016/j.chom.2011.04.015
Krishnamurthy, S. et al. CRISPR screens identify Toxoplasma genes that determine parasite fitness in interferon gamma-stimulated human cells. mBio 14, e0006023 (2023).
pubmed: 36916910
doi: 10.1128/mbio.00060-23
Wang, Y. et al. Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages. Nat. Commun. 11, 5258 (2020).
pubmed: 33067458
pmcid: 7567896
doi: 10.1038/s41467-020-18991-8
Young, J. et al. A CRISPR platform for targeted in vivo screens identifies Toxoplasma gondii virulence factors in mice. Nat. Commun. 10, 3963 (2019).
pubmed: 31481656
pmcid: 6722137
doi: 10.1038/s41467-019-11855-w
Sangare, L. O. et al. In vivo CRISPR screen identifies TgWIP as a Toxoplasma modulator of dendritic cell migration. Cell Host Microbe 26, 478–492 (2019).
pubmed: 31600500
pmcid: 7060943
doi: 10.1016/j.chom.2019.09.008
Butterworth, S. et al. Toxoplasma gondii virulence factor ROP1 reduces parasite susceptibility to murine and human innate immune restriction. PLoS Pathog. 18, e1011021 (2022).
pubmed: 36476844
pmcid: 9762571
doi: 10.1371/journal.ppat.1011021
Butterworth, S. et al. High-throughput identification of Toxoplasma gondii effector proteins that target host cell transcription. Cell Host Microbe 31, 1748–1762 (2023).
pubmed: 37827122
doi: 10.1016/j.chom.2023.09.003
Mageswaran, S. K. et al. In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems. Nat. Commun. 12, 4983 (2021).
pubmed: 34404783
pmcid: 8371170
doi: 10.1038/s41467-021-25309-9
Segev-Zarko, L. A. et al. Cryo-electron tomography with mixed-scale dense neural networks reveals key steps in deployment of Toxoplasma invasion machinery. PNAS Nexus 1, pgac183 (2022).
pubmed: 36329726
pmcid: 9615128
doi: 10.1093/pnasnexus/pgac183
Aquilini, E. et al. An Alveolata secretory machinery adapted to parasite host cell invasion. Nat. Microbiol 6, 425–434 (2021).
pubmed: 33495622
pmcid: 8886610
doi: 10.1038/s41564-020-00854-z
Koshy, A. A. et al. Toxoplasma co-opts host cells it does not invade. PLoS Pathog. 8, e1002825 (2012).
pubmed: 22910631
pmcid: 3406079
doi: 10.1371/journal.ppat.1002825
Cabral, C. M. et al. Neurons are the primary target cell for the brain-tropic intracellular parasite Toxoplasma gondii. PLoS Pathog. 12, e1005447 (2016).
pubmed: 26895155
pmcid: 4760770
doi: 10.1371/journal.ppat.1005447
Bougdour, A. et al. Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression. Cell Host Microbe 13, 489–500 (2013).
pubmed: 23601110
doi: 10.1016/j.chom.2013.03.002
Gay, G. et al. Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses. J. Exp. Med. 213, 1779–1798 (2016).
pubmed: 27503074
pmcid: 4995087
doi: 10.1084/jem.20160340
Olias, P., Etheridge, R. D., Zhang, Y., Holtzman, M. J. & Sibley, L. D. Toxoplasma effector recruits the Mi-2/NuRD complex to repress STAT1 transcription and block IFN-γ-dependent gene expression. Cell Host Microbe 20, 72–82 (2016).
pubmed: 27414498
pmcid: 4947229
doi: 10.1016/j.chom.2016.06.006
Braun, L. et al. A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation. J. Exp. Med. 210, 2071–2086 (2013).
pubmed: 24043761
pmcid: 3782045
doi: 10.1084/jem.20130103
He, H. et al. Characterization of a Toxoplasma effector uncovers an alternative GSK3/β-catenin-regulatory pathway of inflammation. eLife https://doi.org/10.7554/eLife.39887 (2018).
Rosenberg, A. & Sibley, L. D. Toxoplasma gondii secreted effectors co-opt host repressor complexes to inhibit necroptosis. Cell Host Microbe 29, 1186–1198 (2021).
pubmed: 34043960
pmcid: 8711274
doi: 10.1016/j.chom.2021.04.016
Tomita, T. et al. Toxoplasma gondii matrix antigen 1 is a secreted immunomodulatory effector. mBio https://doi.org/10.1128/mBio.00603-21 (2021).
Ma, J. S. et al. Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6. J. Exp. Med. 211, 2013–2032 (2014).
pubmed: 25225460
pmcid: 4172224
doi: 10.1084/jem.20131272
Ten Hoeve, A. L. et al. The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages. Cell Host Microbe 30, 1570–1588 (2022).
pubmed: 36309013
pmcid: 9710525
doi: 10.1016/j.chom.2022.10.001
Alaganan, A., Fentress, S. J., Tang, K., Wang, Q. & Sibley, L. D. Toxoplasma GRA7 effector increases turnover of immunity-related GTPases and contributes to acute virulence in the mouse. Proc. Natl Acad. Sci. USA 111, 1126–1131 (2014).
pubmed: 24390541
pmcid: 3903209
doi: 10.1073/pnas.1313501111
Braun, L. et al. The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2. Nat. Microbiol. 4, 1208–1220 (2019).
pubmed: 31036909
pmcid: 6591128
doi: 10.1038/s41564-019-0431-8
Panas, M. W., Naor, A., Cygan, A. M. & Boothroyd, J. C. Toxoplasma controls host cyclin E expression through the use of a novel MYR1-dependent effector protein, HCE1. mBio https://doi.org/10.1128/mBio.00674-19 (2019).
Tomita, T., Guevara, R. B., Shah, L. M., Afrifa, A. Y. & Weiss, L. M. Secreted effectors modulating immune responses to Toxoplasma gondii. Life https://doi.org/10.3390/life11090988 (2021).
Panas, M. W. & Boothroyd, J. C. Seizing control: How dense granule effector proteins enable Toxoplasma to take charge. Mol. Microbiol. 115, 466–477 (2021).
pubmed: 33400323
pmcid: 8344355
doi: 10.1111/mmi.14679
Hakimi, M. A. Epigenetic reprogramming in host–parasite coevolution: the Toxoplasma paradigm. Annu Rev. Microbiol. 76, 135–155 (2022).
pubmed: 35587934
doi: 10.1146/annurev-micro-041320-011520
Marti, M., Good, R. T., Rug, M., Knuepfer, E. & Cowman, A. F. Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science 306, 1930–1933 (2004).
pubmed: 15591202
doi: 10.1126/science.1102452
Hiller, N. L. et al. A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science 306, 1934–1937 (2004).
pubmed: 15591203
doi: 10.1126/science.1102737
Chang, H. H. et al. N-terminal processing of proteins exported by malaria parasites. Mol. Biochem. Parasitol. 160, 107–115 (2008).
pubmed: 18534695
pmcid: 2922945
doi: 10.1016/j.molbiopara.2008.04.011
Boddey, J. A. et al. An aspartyl protease directs malaria effector proteins to the host cell. Nature 463, 627–631 (2010).
pubmed: 20130643
pmcid: 2818761
doi: 10.1038/nature08728
Boddey, J. A., Moritz, R. L., Simpson, R. J. & Cowman, A. F. Role of the Plasmodium export element in trafficking parasite proteins to the infected erythrocyte. Traffic 10, 285–299 (2009).
pubmed: 19055692
pmcid: 2682620
doi: 10.1111/j.1600-0854.2008.00864.x
Dogga, S. K. et al. A druggable secretory protein maturase of Toxoplasma essential for invasion and egress. eLife https://doi.org/10.7554/eLife.27480 (2017).
Pelle, K. G. et al. Shared elements of host-targeting pathways among apicomplexan parasites of differing lifestyles. Cell Microbiol. 17, 1618–1639 (2015).
pubmed: 25996544
doi: 10.1111/cmi.12460
Coffey, M. J. et al. An aspartyl protease defines a novel pathway for export of Toxoplasma proteins into the host cell. eLife https://doi.org/10.7554/eLife.10809 (2015).
Hammoudi, P. M. et al. Fundamental roles of the Golgi-associated Toxoplasma aspartyl protease, ASP5, at the host–parasite interface. PLoS Pathog. 11, e1005211 (2015).
pubmed: 26473595
pmcid: 4608785
doi: 10.1371/journal.ppat.1005211
Curt-Varesano, A., Braun, L., Ranquet, C., Hakimi, M. A. & Bougdour, A. The aspartyl protease TgASP5 mediates the export of the Toxoplasma GRA16 and GRA24 effectors into host cells. Cell Microbiol. 18, 151–167 (2016).
pubmed: 26270241
doi: 10.1111/cmi.12498
Coffey, M. J. et al. Aspartyl protease 5 matures dense granule proteins that reside at the host–parasite interface in Toxoplasma gondii. mBio https://doi.org/10.1128/mBio.01796-18 (2018).
de Koning-Ward, T. F., Dixon, M. W., Tilley, L. & Gilson, P. R. Plasmodium species: master renovators of their host cells. Nat. Rev. Microbiol. 14, 494–507 (2016).
pubmed: 27374802
doi: 10.1038/nrmicro.2016.79
Marapana, D. S. et al. Plasmepsin V cleaves malaria effector proteins in a distinct endoplasmic reticulum translocation interactome for export to the erythrocyte. Nat. Microbiol. 3, 1010–1022 (2018).
pubmed: 30127496
doi: 10.1038/s41564-018-0219-2
Franco, M. et al. A novel secreted protein, MYR1, is central to Toxoplasma’s manipulation of host cells. mBio 7, e02231-15 (2016).
pubmed: 26838724
pmcid: 4742717
doi: 10.1128/mBio.02231-15
Cygan, A. M. et al. Coimmunoprecipitation with MYR1 identifies three additional proteins within the Toxoplasma gondii parasitophorous vacuole required for translocation of dense granule effectors into host cells. mSphere https://doi.org/10.1128/mSphere.00858-19 (2020).
Marino, N. D. et al. Identification of a novel protein complex essential for effector translocation across the parasitophorous vacuole membrane of Toxoplasma gondii. PLoS Pathog. 14, e1006828 (2018).
pubmed: 29357375
pmcid: 5794187
doi: 10.1371/journal.ppat.1006828
Beck, J. R., Muralidharan, V., Oksman, A. & Goldberg, D. E. PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes. Nature 511, 592–595 (2014).
pubmed: 25043010
pmcid: 4130291
doi: 10.1038/nature13574
Elsworth, B. et al. PTEX is an essential nexus for protein export in malaria parasites. Nature 511, 587–591 (2014).
pubmed: 25043043
doi: 10.1038/nature13555
de Koning-Ward, T. F. et al. A newly discovered protein export machine in malaria parasites. Nature 459, 945–949 (2009).
pubmed: 19536257
pmcid: 2725363
doi: 10.1038/nature08104
Ho, C. M. et al. Malaria parasite translocon structure and mechanism of effector export. Nature 561, 70–75 (2018).
pubmed: 30150771
pmcid: 6555636
doi: 10.1038/s41586-018-0469-4
Gold, D. A. et al. The Toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole. Cell Host Microbe 17, 642–652 (2015).
pubmed: 25974303
pmcid: 4435723
doi: 10.1016/j.chom.2015.04.003
Blakely, W. J., Holmes, M. J. & Arrizabalaga, G. The secreted acid phosphatase domain-containing GRA44 from Toxoplasma gondii is required for c-Myc induction in infected cells. mSphere https://doi.org/10.1128/mSphere.00877-19 (2020).
Zhao, Y. G. & Zhang, H. Phase separation in membrane biology: the interplay between membrane-bound organelles and membraneless condensates. Dev. Cell 55, 30–44 (2020).
pubmed: 32726575
doi: 10.1016/j.devcel.2020.06.033
Treeck, M., Sanders, J. L., Elias, J. E. & Boothroyd, J. C. The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites’ boundaries. Cell Host Microbe 10, 410–419 (2011).
pubmed: 22018241
pmcid: 3254672
doi: 10.1016/j.chom.2011.09.004
Panas, M. W. et al. Translocation of dense granule effectors across the parasitophorous vacuole membrane in Toxoplasma-infected cells requires the activity of ROP17, a rhoptry protein kinase. mSphere https://doi.org/10.1128/mSphere.00276-19 (2019).
Drewry, L. L. et al. The secreted kinase ROP17 promotes Toxoplasma gondii dissemination by hijacking monocyte tissue migration. Nat. Microbiol. 4, 1951–1963 (2019).
pubmed: 31332383
pmcid: 6814536
doi: 10.1038/s41564-019-0504-8
Nadipuram, S. M. et al. In vivo biotinylation of the Toxoplasma parasitophorous vacuole reveals novel dense granule proteins important for parasite growth and pathogenesis. mBio https://doi.org/10.1128/mBio.00808-16 (2016).
Mayoral, J. et al. Toxoplasma gondii PPM3C, a secreted protein phosphatase, affects parasitophorous vacuole effector export. PLoS Pathog. 16, e1008771 (2020).
pubmed: 33370417
pmcid: 7793252
doi: 10.1371/journal.ppat.1008771
Naor, A. et al. MYR1-dependent effectors are the major drivers of a host cell’s early response to Toxoplasma, including counteracting MYR1-independent effects. mBio https://doi.org/10.1128/mBio.02401-17 (2018).
Rastogi, S., Xue, Y., Quake, S. R. & Boothroyd, J. C. Differential impacts on host transcription by ROP and GRA effectors from the intracellular parasite Toxoplasma gondii. mBio https://doi.org/10.1128/mBio.00182-20 (2020).
Chen, L. et al. The Toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses. J. Exp. Med. https://doi.org/10.1084/jem.20181757 (2020).
Fouts, A. E. & Boothroyd, J. C. Infection with Toxoplasma gondii bradyzoites has a diminished impact on host transcript levels relative to tachyzoite infection. Infect. Immun. 75, 634–642 (2007).
pubmed: 17088349
doi: 10.1128/IAI.01228-06
Seizova, S. et al. Transcriptional modification of host cells harboring Toxoplasma gondii bradyzoites prevents IFN gamma-mediated cell death. Cell Host Microbe 30, 232–247 (2022).
pubmed: 34921775
doi: 10.1016/j.chom.2021.11.012
Sugi, T. et al. Single cell transcriptomes of in vitro bradyzoite infected cells reveals Toxoplasma gondii stage dependent host cell alterations. Front. Cell Infect. Microbiol. 12, 848693 (2022).
pubmed: 35372115
pmcid: 8964302
doi: 10.3389/fcimb.2022.848693
Rahman, M. T. et al. The redox homeostasis of skeletal muscle cells regulates stage differentiation of Toxoplasma gondii. Front Cell Infect. Microbiol. 11, 798549 (2021).
pubmed: 34881198
pmcid: 8646093
doi: 10.3389/fcimb.2021.798549
Swierzy, I. J. et al. Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host–parasite interactions. Sci. Rep. 7, 7229 (2017).
pubmed: 28775382
pmcid: 5543063
doi: 10.1038/s41598-017-07838-w
Christiansen, C. et al. In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization. Nat. Commun. 13, 1168 (2022).
pubmed: 35246532
pmcid: 8897399
doi: 10.1038/s41467-022-28730-w
Waldman, B. S. et al. Identification of a master regulator of differentiation in Toxoplasma. Cell 180, 359–372 (2020).
pubmed: 31955846
pmcid: 6978799
doi: 10.1016/j.cell.2019.12.013
Lemgruber, L., Lupetti, P., Martins-Duarte, E. S., De Souza, W. & Vommaro, R. C. The organization of the wall filaments and characterization of the matrix structures of Toxoplasma gondii cyst form. Cell Microbiol. 13, 1920–1932 (2011).
pubmed: 21899696
doi: 10.1111/j.1462-5822.2011.01681.x
Kannan, G., Thaprawat, P., Schultz, T. L. & Carruthers, V. B. Acquisition of host cytosolic protein by Toxoplasma gondii bradyzoites. mSphere https://doi.org/10.1128/mSphere.00934-20 (2021).
Paredes-Santos, T., Wang, Y., Waldman, B., Lourido, S. & Saeij, J. P. The GRA17 parasitophorous vacuole membrane permeability pore contributes to bradyzoite viability. Front. Cell Infect. Microbiol. 9, 321 (2019).
pubmed: 31572690
pmcid: 6751312
doi: 10.3389/fcimb.2019.00321
Tu, V. et al. Enrichment and proteomic characterization of the cyst wall from in vitro Toxoplasma gondii cysts. mBio https://doi.org/10.1128/mBio.00469-19 (2019).
Krishnamurthy, S. & Saeij, J. P. J. Toxoplasma does not secrete the GRA16 and GRA24 effectors beyond the parasitophorous vacuole membrane of tissue cysts. Front. Cell Infect. Microbiol. 8, 366 (2018).
pubmed: 30406043
pmcid: 6201044
doi: 10.3389/fcimb.2018.00366
Dogga, S. K. et al. Importance of aspartyl protease 5 in the establishment of the intracellular niche during acute and chronic infection of Toxoplasma gondii. Mol. Microbiol. 118, 601–622 (2022).
pubmed: 36210525
doi: 10.1111/mmi.14987
Mayoral, J., Shamamian, P. Jr & Weiss, L. M. In vitro characterization of protein effector export in the bradyzoite stage of Toxoplasma gondii. mBio https://doi.org/10.1128/mBio.00046-20 (2020).
Fritz, H. M. et al. Transcriptomic analysis of Toxoplasma development reveals many novel functions and structures specific to sporozoites and oocysts. PLoS ONE 7, e29998 (2012).
pubmed: 22347997
pmcid: 3278417
doi: 10.1371/journal.pone.0029998
Guiton, P. S., Sagawa, J. M., Fritz, H. M. & Boothroyd, J. C. An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells. PLoS ONE 12, e0173018 (2017).
pubmed: 28362800
pmcid: 5376300
doi: 10.1371/journal.pone.0173018
Ramakrishnan, C. et al. An experimental genetically attenuated live vaccine to prevent transmission of Toxoplasma gondii by cats. Sci. Rep. 9, 1474 (2019).
pubmed: 30728393
pmcid: 6365665
doi: 10.1038/s41598-018-37671-8
Fritz, H. M., Bowyer, P. W., Bogyo, M., Conrad, P. A. & Boothroyd, J. C. Proteomic analysis of fractionated Toxoplasma oocysts reveals clues to their environmental resistance. PLoS ONE 7, e29955 (2012).
pubmed: 22279555
pmcid: 3261165
doi: 10.1371/journal.pone.0029955
Possenti, A. et al. Global proteomic analysis of the oocyst/sporozoite of Toxoplasma gondii reveals commitment to a host-independent lifestyle. BMC Genom. 14, 183 (2013).
doi: 10.1186/1471-2164-14-183
Hehl, A. B. et al. Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes. BMC Genom. 16, 66 (2015).
doi: 10.1186/s12864-015-1225-x
Martorelli Di Genova, B., Wilson, S. K., Dubey, J. P. & Knoll, L. J. Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction. PLoS Biol. 17, e3000364 (2019).
pubmed: 31430281
pmcid: 6701743
doi: 10.1371/journal.pbio.3000364
Rosowski, E. E. et al. Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein. J. Exp. Med. 208, 195–212 (2011).
pubmed: 21199955
pmcid: 3023140
doi: 10.1084/jem.20100717