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Jean-françois Dubremetz - One of the best experts on this subject based on the ideXlab platform.

  • Molecular characterisation of a Cryptosporidium parvum Rhoptry protein candidate related to the Rhoptry neck Proteins TgRON1 of Toxoplasma gondii and PfASP of Plasmodium falciparum.
    Molecular and Biochemical Parasitology, 2012
    Co-Authors: Elisabetta Valentini, Simona Cherchi, Alessia Possenti, Jean-françois Dubremetz, Edoardo Pozio, Furio Spano
    Abstract:

    Abstract Given the lack of knowledge on the Rhoptry Proteins of Cryptosporidium parvum , we searched for putative members of this protein class in the CryptoDB database using as queries known Toxoplasma gondii Rhoptry molecules. We cloned a C. parvum sporozoite cDNA of 4269 bp encoding the sushi domain-containing protein cgd8_2530, which shared low amino acid sequence identity, yet a highly conserved domain architecture with the Rhoptry neck Proteins TgRON1 of T. gondii and PfASP of Plasmodium falciparum . On denaturing and native gels, cgd8_2530 migrated at approximately 150 and 1000 kDa, respectively, suggesting an involvement in a multi-subunit protein complex. Immunoflorescence localised cgd8_2530 to a single, elongated area anterior to sporozoite micronemes and showed protein relocation to the parasite–host cell interface in early epicellular stages. Our data strongly suggest a Rhoptry localization for the newly characterised protein, which was therefore renamed C. parvum putative Rhoptry protein-1 (CpPRP1).

  • Manipulation du système immunitaire par le parasite Toxoplasma gondii
    Medecine sciences : M S, 2008
    Co-Authors: Dominique Buzoni-gatel, Jean-françois Dubremetz, Catherine Werts
    Abstract:

    Toxoplasma gondii is an intracellular parasite that frequently infects a large spectrum of warm-blooded animals. This parasite induces abortion and establishes both chronic and silent infections, particularly in the brain. The chronic infection is therefore a permanent threat for the host in cases of immunosuppression. Parasite penetration into the host activates a strong anti-parasite immune response, but is also used by the parasite to chronically persist. In the present paper, we discuss the data obtained in the laboratory of John Boothroyd that reports the molecular cross talk between the parasite Rhoptry Proteins and the host cell. During host cell invasion, rhoptries participate to the constitution of the mobile junction that drives the parasite into the host cell, while building the parasitophorus vacuole in which the parasite grows. Some soluble rhoptries, such as ROP16, are shed into the cytoplasm, and then reach the nucleus where they can eventually impact different signaling pathways such as STAT3/6, key molecules in the immune response establishment.

  • Kiss and spit: the dual roles of Toxoplasma rhoptries
    Nature Reviews Microbiology, 2008
    Co-Authors: John C. Boothroyd, Jean-françois Dubremetz
    Abstract:

    Toxoplasma gondii rhoptries are dedicated secretory organelles that are involved in the mechanics of invasion and commandeering of the infected host cell. Rhoptry Proteins collaborate with Proteins that are released from another secretory organelle, the microneme, to create a circular moving junction at the ring of contact between the parasite and host plasma membranes. Rhoptry Proteins, including protein kinases and phosphatases, are injected into the host cell, where they affect host functions. There is a huge amount of allelic variation in the genes coding for Rhoptry Proteins and this has a dramatic effect on the outcome of infection. Host range might have been the selective pressure for allelic sequence drift in Rhoptry genes. John C. Boothroyd and Jean-Francois Dubremetz review the roles of the apical Rhoptry organelles in cell invasion by Apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. They propose a model in which an expansion of host range might have been the selective pressure for Rhoptry-protein evolution. Toxoplasma gondii is a single-celled, eukaryotic parasite that can only reproduce inside a host cell. Upon entry, this Apicomplexan parasite co-opts host functions for its own purposes. An unusual set of apical organelles, named rhoptries, contain some of the machinery that is used by T. gondii both for invasion and to commandeer host functions. Of particular interest are a group of injected protein kinases that are among the most variable of all the T. gondii Proteins. At least one of these kinases has a major effect on host-gene expression, including the modulation of key regulators of the immune response. Here, we discuss these recent findings and use them to propose a model in which an expansion of host range is a major force that drives Rhoptry-protein evolution.

  • ROP18 is a Rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii.
    PLoS Pathogens, 2007
    Co-Authors: Hiba El Hajj, Maryse Lebrun, Henri Vial, Gilles Labesse, Stefan T Arold, Jean-françois Dubremetz
    Abstract:

    Toxoplasma gondii is an obligate intracellular parasite for which the discharge of apical organelles named rhoptries is a key event in host cell invasion. Among Rhoptry Proteins, ROP2, which is the prototype of a large protein family, is translocated in the parasitophorous vacuole membrane during invasion. The ROP2 family members are related to protein-kinases, but only some of them are predicted to be catalytically active, and none of the latter has been characterized so far. We show here that ROP18, a member of the ROP2 family, is located in the rhoptries and re-localises at the parasitophorous vacuole membrane during invasion. We demonstrate that a recombinant ROP18 catalytic domain (amino acids 243-539) possesses a protein-kinase activity and phosphorylate parasitic substrates, especially a 70-kDa protein of tachyzoites. Furthermore, we show that overexpression of ROP18 in transgenic parasites causes a dramatic increase in intra-vacuolar parasite multiplication rate, which is correlated with kinase activity. Therefore, we demonstrate, to our knowledge for the first time, that rhoptries can discharge active protein-kinases upon host cell invasion, which can exert a long-lasting effect on intracellular parasite development and virulence.

  • The ROP2 family of Toxoplasma gondii Rhoptry Proteins: proteomic and genomic characterization and molecular modeling.
    Proteomics, 2006
    Co-Authors: Hiba El Hajj, Emmanuelle Demey, Joël Poncet, Maryse Lebrun, Nathalie Galéotti, Marie Noëlle Fourmaux, Odile Mercereau-puijalon, Henri Vial, Gilles Labesse, Jean-françois Dubremetz
    Abstract:

    Four Rhoptry Proteins (ROP) of Toxoplasma gondii previously identified with mAb have been affinity purified and analyzed by MS; the data obtained allowed the genomic sequences to be assigned to these Proteins. As previously suggested for some of them by antibody crossreactivity, these Proteins were shown to belong to a family, the prototype of which being ROP2. We describe here the Proteins ROP2, 4, 5, and 7. These four Proteins correspond to the most abundant products of a gene family that comprises several members which we have identified in genomic and EST libraries. Eight additional sequences were found and we have cloned four of them. All members of the ROP2 family contain a protein-kinase-like domain, but only some of them possess a bona fide kinase catalytic site. Molecular modeling of the kinase domain demonstrates the conservation of residues critical for the stabilization of the protein-kinase fold, especially within a hydrophobic segment described so far as transmembrane and which appears as an helix buried inside the protein. The concomitant synthesis of these ROPs by T. gondii tachyzoites suggests a specific role for each of these Proteins, especially in the early interaction with the host cell upon invasion.

John C. Boothroyd - One of the best experts on this subject based on the ideXlab platform.

  • Differentially expressed genes encoding Rhoptry Proteins.
    2017
    Co-Authors: Pascale S. Guiton, Janelle M. Sagawa, Heather M. Fritz, John C. Boothroyd
    Abstract:

    Differentially expressed genes encoding Rhoptry Proteins.

  • association of host mitochondria with the parasitophorous vacuole during toxoplasma infection is not dependent on Rhoptry Proteins rop2 8
    International Journal for Parasitology, 2010
    Co-Authors: Lena Pernas, John C. Boothroyd
    Abstract:

    Previous work has proposed Rhoptry protein 2 (ROP2) as the physical link that tethers host mitochondria to the parasitophorous vacuole membrane (PVM) surrounding the intracellular parasite, Toxoplasma gondii. A recent analysis of the ROP2 structure, however, raised questions about this model. To determine whether ROP2 is necessary, we created a parasite line that lacks the entire ROP2 locus consisting of the three closely related genes, ROP2a, ROP2b and ROP8. We show that this knockout mutant retains the ability to recruit host mitochondria in a manner that is indistinguishable from the parental strain, re-opening the question of which molecules mediate this association.

  • 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, 2008
    Co-Authors: Joe Dan Dunn, Sandeep Ravindran, Seonkyeong Kim, John C. Boothroyd
    Abstract:

    The obligate intracellular parasite Toxoplasma gondii infects warm-blooded animals throughout the world and is an opportunistic pathogen of humans. As it invades a host cell, Toxoplasma forms a novel organelle, the parasitophorous vacuole, in which it resides during its intracellular development. The parasite modifies the parasitophorous vacuole and its host cell with numerous Proteins delivered from rhoptries and dense granules, which are secretory organelles unique to the phylum Apicomplexa. For the majority of these Proteins, little is known other than their localization. Here we show that the dense granule protein GRA7 is phosphorylated but only in the presence of host cells. Within 10 min of invasion, GRA7 is present in strand-like structures in the host cytosol that contain Rhoptry Proteins. GRA7 strands also contain GRA1 and GRA3. Independently of its phosphorylation state, GRA7 associates with the Rhoptry Proteins ROP2 and ROP4 in infected host cells. This is the first report of interactions between Proteins secreted from rhoptries and dense granules.

  • Kiss and spit: the dual roles of Toxoplasma rhoptries
    Nature Reviews Microbiology, 2008
    Co-Authors: John C. Boothroyd, Jean-françois Dubremetz
    Abstract:

    Toxoplasma gondii rhoptries are dedicated secretory organelles that are involved in the mechanics of invasion and commandeering of the infected host cell. Rhoptry Proteins collaborate with Proteins that are released from another secretory organelle, the microneme, to create a circular moving junction at the ring of contact between the parasite and host plasma membranes. Rhoptry Proteins, including protein kinases and phosphatases, are injected into the host cell, where they affect host functions. There is a huge amount of allelic variation in the genes coding for Rhoptry Proteins and this has a dramatic effect on the outcome of infection. Host range might have been the selective pressure for allelic sequence drift in Rhoptry genes. John C. Boothroyd and Jean-Francois Dubremetz review the roles of the apical Rhoptry organelles in cell invasion by Apicomplexan parasites such as Toxoplasma gondii and Plasmodium spp. They propose a model in which an expansion of host range might have been the selective pressure for Rhoptry-protein evolution. Toxoplasma gondii is a single-celled, eukaryotic parasite that can only reproduce inside a host cell. Upon entry, this Apicomplexan parasite co-opts host functions for its own purposes. An unusual set of apical organelles, named rhoptries, contain some of the machinery that is used by T. gondii both for invasion and to commandeer host functions. Of particular interest are a group of injected protein kinases that are among the most variable of all the T. gondii Proteins. At least one of these kinases has a major effect on host-gene expression, including the modulation of key regulators of the immune response. Here, we discuss these recent findings and use them to propose a model in which an expansion of host range is a major force that drives Rhoptry-protein evolution.

  • A novel Rhoptry protein in Toxoplasma gondii bradyzoites and merozoites
    Molecular and biochemical parasitology, 2005
    Co-Authors: Jodi A. Schwarz, David J P Ferguson, Ashley E. Fouts, Craig A. Cummings, John C. Boothroyd
    Abstract:

    The secretory organelles of Toxoplasma gondii orchestrate invasion of the host cell and establish the parasitophorous vacuole. Although much has been learned about the roles played by these organelles in invasion by the tachyzoite stage, little is known about the contents or functions of these organelles during bradyzoite development or pathogenesis. We identified a novel protein that localizes to the rhoptries of the bradyzoite stage, but is absent from the tachyzoite stage. This protein, BRP1, first appears in the nascent rhoptries during the first division of bradyzoite stage development. We observed secretion of BRP1 and other Rhoptry Proteins into the parasitophorous vacuole during bradyzoite development in vitro, but there was no evidence that this occurs in vivo. Brp1 knockout parasites did not appear to have any developmental or growth defects in vitro, and were able to establish infections in mice both as tachyzoites (via intraperitoneal injection of in vitro-derived tachyzoites) or bradyzoites (via oral gavage using cysts harvested from mouse brain). Mice infected using brain cysts from the brp1 knockout or the control strain developed similar numbers and sizes of brain cysts. Thus BRP1 does not appear to play an essential role in development of the bradyzoite stage, development of brain cysts, or oral infection of new hosts, at least in the mouse model used here. Since we also observed that BRP1 is expressed in the merozoite stages in the gut of infected cats, the coccidian phase of the life cycle may be where BRP1 plays its most important role.

Jeroen P J Saeij - One of the best experts on this subject based on the ideXlab platform.

  • identification of three novel toxoplasma gondii Rhoptry Proteins
    International Journal for Parasitology, 2014
    Co-Authors: Ana Camejo, Daniel Gold, Kiva Mcfetridge, Lindsay Julien, Ninghan Yang, Kirk D C Jensen, Jeroen P J Saeij
    Abstract:

    The rhoptries are key secretory organelles from apicomplexan parasites that contain Proteins involved in invasion and modulation of the host cell. Some Rhoptry Proteins are restricted to the posterior bulb (ROPs) and others to the anterior neck (RONs). As many Rhoptry Proteins have been shown to be key players in Toxoplasma invasion and virulence, it is important to identify, understand and characterise the biological function of the components of the rhoptries. In this report, we identified putative novel Rhoptry genes by identifying Toxoplasma genes with similar cyclical expression profiles as known Rhoptry protein encoding genes. Using this approach we identified two new Rhoptry bulb (ROP47 and ROP48) and one new Rhoptry neck protein (RON12). ROP47 is secreted and traffics to the host cell nucleus, RON12 was not detected at the moving junction during invasion. Deletion of ROP47 or ROP48 in a type II strain did not show major influence in in vitro growth or virulence in mice.

  • strain specific activation of the nf κb pathway by gra15 a novel toxoplasma gondii dense granule protein
    Journal of Experimental Medicine, 2011
    Co-Authors: Emily E Rosowski, Lindsay Julien, Kirk D C Jensen, Lauren B Rodda, Rogier A Gaiser, Jeroen P J Saeij
    Abstract:

    NF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate the NF-κB pathway, the parasite-derived effectors involved are unknown. We determined that type II strains of T. gondii activate more NF-κB than type I or type III strains, and using forward genetics we found that this difference is a result of the polymorphic protein GRA15, a novel dense granule protein which T. gondii secretes into the host cell upon invasion. A GRA15-deficient type II strain has a severe defect in both NF-κB nuclear translocation and NF-κB-mediated transcription. Furthermore, human cells expressing type II GRA15 also activate NF-κB, demonstrating that GRA15 alone is sufficient for NF-κB activation. Along with the Rhoptry protein ROP16, GRA15 is responsible for a large part of the strain differences in the induction of IL-12 secretion by infected mouse macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II strain grows faster compared with wild-type, most likely through its reduced induction of IFN-γ. These results show for the first time that a dense granule protein can modulate host signaling pathways, and dense granule Proteins can therefore join Rhoptry Proteins in T. gondii's host cell-modifying arsenal.

Henryka Dlugonska - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of three recombinant multi antigenic vaccines composed of surface and secretory antigens of toxoplasma gondii in murine models of experimental toxoplasmosis
    Vaccine, 2011
    Co-Authors: Bozena Dziadek, Jaroslaw Dziadek, Justyna Gatkowska, Anna Brzostek, Katarzyna Dzitko, Marcin M Grzybowski, Henryka Dlugonska
    Abstract:

    The great clinical and economical impact of Toxoplasma gondii infections makes the development of an effective vaccine for controlling toxoplasmosis an extremely important aim. In the presented study, we evaluate the protective and immunogenic properties of three recombinant subunit vaccines composed of rROP2 + rGRA4 + rSAG1, rROP2 + rROP4 + rGRA4 and rROP2 + rROP4 + rSAG1 Proteins of T. gondii in an experimental toxoplasmosis model in the C3H/HeJ and C57BL/6 mouse strains. All three recombinant vaccines induced partial protection as measured by the reduction of brain cyst burden following challenge with five tissue cysts of the low virulence DX T. gondii strain. The level of protection was dependent on the antigen composition of the vaccine and the genetic background of the laboratory animals. The strongest protection against chronic toxoplasmosis was induced in both C3H/HeJ and C57BL/6 mice by the mixture of Rhoptry Proteins rROP2 and rROP4 combined with tachyzoite major protein rSAG1. The average parasite burden in these groups of mice was reduced by 71% and 90%, respectively, compared to non-vaccinated mice. The observed protective effect was related to the vaccine-induced cellular and humoral immune responses, as measured by the antigen-induced release of the Th1 cytokines IFN- and IL-2, the antigenstimulated proliferation of spleen cells of vaccinated animals in comparison to control animals and the development of systemic antigen-specific IgG1 and IgG2a (C3H/HeJ) or IgG2c (C57BL/6) antibodies. Our studies show that recombinant rROP2, rROP4, rGRA4 and rSAG1 antigens may be promising candidates for a subunit vaccine against toxoplasmosis. Additionally, we demonstrate that the ideal composition of vaccine antigens can be equally effective in mice with different genetic backgrounds and variable levels of innate resistance to toxoplasmosis, resulting in strong protection against T. gondii invasion.

  • toxoplasma gondii the immunogenic and protective efficacy of recombinant rop2 and rop4 Rhoptry Proteins in murine experimental toxoplasmosis
    Experimental Parasitology, 2009
    Co-Authors: Bozena Dziadek, Jaroslaw Dziadek, Justyna Gatkowska, Anna Brzostek, Katarzyna Dzitko, Henryka Dlugonska
    Abstract:

    Abstract Toxoplasmosis is a one of the most world-wide spread zoonosis representing a very serious clinical and veterinary problem. In the presented study, we evaluated the protective efficacy of a combined recombinant ROP2 and ROP4 subunit vaccine in a chronic Toxoplasma gondii infection in mice. The recombinant ROP2 (rROP2) and ROP4 (rROP4) Proteins were cloned and expressed in Escherichia coli and then used for the immunization of C3H/HeJ mice. Both antigens generated a strong systemic mixed Th1/Th2 response polarized towards IgG1 antibody isotype. In contrast to rROP2 stimulating only the specific IL-2 release, rROP4 and crude toxoplasma lysate antigen (TLA) used as a source of native forms of the parasite Proteins induced significant proliferation of splenocytes and specific production of IFN-γ as well as IL-2, the Th1-type cytokines. Challenge of rROP2 and rROP4-vaccinated mice with cysts of low virulent T. gondii DX strain resulted in a partial protection effect with a significantly lower brain parasites load when compared with control animals. In the immunized group of mice the brain cysts number was reduced by nearly 46% as was determined in two independent experiments. These results suggest that, similar to ROP2, Rhoptry protein ROP4 could be a very good candidate for future anti-T. gondii multicomponent vaccine based on the recombinant forms of different parasite Proteins.

  • identification of toxoplasma gondii Proteins binding human lactoferrin a new aspect of Rhoptry Proteins function
    Experimental Parasitology, 2007
    Co-Authors: Bozena Dziadek, Jaroslaw Dziadek, Henryka Dlugonska
    Abstract:

    In this paper, we report on the isolation, purification and identification of two Toxoplasma gondii membrane Proteins binding human lactoferrin. Parasite membrane Proteins were isolated using the commercial Mem-PER Eukaryotic Membrane Protein Extraction System. After purification by lactoferrin affinity chromatography, three protein bands were detected with the molecular mass of 74, 63 and 58 kDa, two of which (63 and 58 kDa) specifically bound biotin labeled human lactoferrin as examined by competitive inhibition. Further identification of latter Proteins by ESI/MS/MS amino acid sequencing technique revealed those Proteins as Toxoplasma ROP4 (band 63 kDa) and ROP2 (band 58 kDa) antigens known to be involved in many mechanisms essential for the parasite pathogenicity, including host lactoferrin acquisition as determined in this study.

  • characterization of tgrop9 p36 a novel Rhoptry protein of toxoplasma gondii tachyzoites identified by t cell clone
    Molecular and Biochemical Parasitology, 2002
    Co-Authors: Gaby Reichmann, Henryka Dlugonska, Hans-georg Fischer
    Abstract:

    T cell clone 3Tx19 detects a Toxoplasma gondii tachyzoite protein which, in high resolution 2D gel electrophoresis, runs at 36 kDa apparent MW with two spots of pI 5.9 and 6.5, thus exhibiting a migration pattern distinct from those of other known Toxoplasma antigens. The sequences of peptide fragments from tryptic digestion of the more prominent protein spot allowed the design of oligonucleotide primers to obtain the coding cDNA sequence. Sequence analysis of cDNA from strain BK revealed a 363 amino acid open reading frame, defined by all nine peptide sequences determined. The deduced protein sequence contains two hydrophobic segments, one near the N-terminus including a predicted signal peptide and a shorter second at the carboxy terminus, but homology to any other known protein is lacking. With synthetic peptides covering the complete primary structure, the epitope for clone 3Tx19 was mapped within the deduced partial sequence, which had remained unconfirmed by tryptic peptides. Antibodies raised against another, putative B cell epitope peptide detected the same two protein spots in 2D gel, indicating that they are antigenically related isoforms. The protein p36 is expressed by T. gondii isolates of all three intraspecies subgroups, but not in the bradyzoite stage. In intracellular tachyzoites, p36 colocalizes with Rhoptry Proteins and has a distribution pattern disparate from that of dense granule and microneme Proteins. Subcellular fractionation indicated that p36 is a soluble constituent of tachyzoites. We suggest that this T cell-stimulatory novel Rhoptry protein of T. gondii be named ROP9. It represents a marker of the tachyzoite stage.

  • Murine Th1 clone defines a 60 kD tachyzoite antigen of Toxoplasma gondii.
    Parasite Immunology, 1997
    Co-Authors: Gaby Reichmann, Henryka Dlugonska, Hans-georg Fischer
    Abstract:

    Toxoplasma gondii-specific murine CD4+ T cell clone 3Tx9 belongs to the Th1 subtype by virtue of secreting high levels of interleukin(IL)-2, interferon-gamma and tumor necrosis factor without producing IL4 and IL10. To characterize the clonal antigen, Toxoplasma lysate-was separated by SDS-PAGE and probed in T cell blot analysis with 3Tx9 T cells, revealing a fraction of about 60 kD molecular weight. This fraction proved highly stimulatory also for CD4+ splenocytes isolated from infected mice. The expression pattern of the relevant 60 kD antigen was determined by challenge of clone 3Tx9 with T. gondii strains from all three intraspecies subgroups and tachyzoites versus bradyzoites isolated from two strains as a source of antigen. While the T cell clone reacted with tachyzoites of all strains tested, bradyzoites lacked antigenic activity. Parallel T cell blot and ELISA confirmed co-migration of the T cell-stimulatory antigen p60 and Rhoptry Proteins ROP1, ROP2,3,4, and ROP5 among which ROP1 is a molecule of similar size and has only been shown on tachyzoites. However, a ROP1 knock-out Toxoplasma mutant still had antigen activity for 3Tx9 T cells. Since the two known tachyzoite-specific Proteins, surface antigens SAG1/p30 and SAG2/p22, have a much lower molecular weight, we suggest that p60 represents a new T. gondii tachyzoite marker which is defined by clone 3Tx9.

Marjorie Maynadier - One of the best experts on this subject based on the ideXlab platform.

  • An Alveolata secretory machinery adapted to parasite host cell invasion
    Nature Microbiology, 2021
    Co-Authors: Eleonora Aquilini, Marta Mendonça Cova, Shrawan Kumar Mageswaran, Nicolas Dos Santos Pacheco, Daniela Sparvoli, Diana Marcela Penarete-vargas, Rania Najm, Arnault Graindorge, Catherine Suarez, Marjorie Maynadier
    Abstract:

    Apicomplexa are unicellular eukaryotes and obligate intracellular parasites, including Plasmodium (the causative agent of malaria) and Toxoplasma (one of the most widespread zoonotic pathogens). Rhoptries, one of their specialized secretory organelles, undergo regulated exocytosis during invasion^ 1 . Rhoptry Proteins are injected directly into the host cell to support invasion and subversion of host immune function^ 2 . The mechanism by which they are discharged is unclear and appears distinct from those in bacteria, yeast, animals and plants. Here, we show that Rhoptry secretion in Apicomplexa shares structural and genetic elements with the exocytic machinery of ciliates, their free-living relatives. Rhoptry exocytosis depends on intramembranous particles in the shape of a rosette embedded into the plasma membrane of the parasite apex. Formation of this rosette requires multiple non-discharge (Nd) Proteins conserved and restricted to Ciliata, Dinoflagellata and Apicomplexa that together constitute the superphylum Alveolata. We identified Nd6 at the site of exocytosis in association with an apical vesicle. Sandwiched between the rosette and the tip of the Rhoptry, this vesicle appears as a central element of the Rhoptry secretion machine. Our results describe a conserved secretion system that was adapted to provide defence for free-living unicellular eukaryotes and host cell injection in intracellular parasites. The architecture and molecular composition of the Rhoptry secretion system in Apicomplexa evolved from an Alveolata-specific fusion machinery ancestry.

  • An Alveolata secretory machinery adapted to parasite host cell invasion
    Nature Microbiology, 2021
    Co-Authors: Eleonora Aquilini, Marta Mendonça Cova, Shrawan Kumar Mageswaran, Nicolas Dos Santos Pacheco, Daniela Sparvoli, Diana Marcela Penarete-vargas, Rania Najm, Arnault Graindorge, Catherine Suarez, Marjorie Maynadier
    Abstract:

    Apicomplexa are unicellular eukaryotes and obligate intracellular parasites, including Plasmodium (the causative agent of malaria) and Toxoplasma (one of the most widespread zoonotic pathogens). Rhoptries, one of their specialized secretory organelles, undergo regulated exocytosis during invasion1. Rhoptry Proteins are injected directly into the host cell to support invasion and subversion of host immune function2. The mechanism by which they are discharged is unclear and appears distinct from those in bacteria, yeast, animals and plants. Here, we show that Rhoptry secretion in Apicomplexa shares structural and genetic elements with the exocytic machinery of ciliates, their free-living relatives. Rhoptry exocytosis depends on intramembranous particles in the shape of a rosette embedded into the plasma membrane of the parasite apex. Formation of this rosette requires multiple non-discharge (Nd) Proteins conserved and restricted to Ciliata, Dinoflagellata and Apicomplexa that together constitute the superphylum Alveolata. We identified Nd6 at the site of exocytosis in association with an apical vesicle. Sandwiched between the rosette and the tip of the Rhoptry, this vesicle appears as a central element of the Rhoptry secretion machine. Our results describe a conserved secretion system that was adapted to provide defence for free-living unicellular eukaryotes and host cell injection in intracellular parasites.