Transport and Trafficking:
            <i>Toxoplasma</i>
            as a Model for
            <i>Plasmodium</i>

Roos, David S.; Crawford, Michael J.; Donald, Robert G. K.; Fohl, Leah M.; Hager, Kristin M.; Kissinger, Jessica C.; Reynolds, Mary G.; Striepen, Boris; Sullivan, William J.

doi:10.1002/9780470515730.ch13

Cited by 22 publications

(8 citation statements)

References 62 publications

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“…Toxoplasma gondii, a distant cousin of Plasmodium, was frequently used as a model organism to fill this gap (Roos et al, 1999). Although knowledge of this apicomplexan parasite is important for understanding Plasmodium biology, the closely related avian malaria species are more likely to use the same mechanisms for interaction with host macrophages.…”

Section: Discussionmentioning

confidence: 99%

Exoerythrocytic development of Plasmodium gallinaceum in the White Leghorn chicken

Frevert¹,

Späth²,

Yee³

2008

International Journal for Parasitology

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Plasmodium gallinaceum typically causes sub-clinical disease with low mortality in its primary host, the Indian jungle fowl Gallus sonnerati. Domestic chickens of European origin, however, are highly susceptible to this avian malaria parasite. Here we describe the development of P. gallinaceum in young White Leghorn chicks with emphasis on the primary exoerythrocytic phase of the infection. Using various regimens for infection, we found that P. gallinaceum induced a transient primary exoerythrocytic infection followed by a fulminant lethal erythrocytic phase. Prerequisite for the appearance of secondary exoerythrocytic stages was the development of a certain level of parasitemia. Once established, secondary exoerythrocytic stages could be propagated from bird to bird for several generations without causing fatalities. Infected brains contained large secondary exoerythrocytic stages in capillary endothelia, while in the liver primary and secondary erythrocytic stages developed primarily in Kupffer cells and remained smaller. At later stages, livers exhibited focal hepatocyte necrosis, Kupffer cell hyperplasia, stellate cell proliferation, inflammatory cell infiltration and granuloma formation. Because P. gallinaceum selectively infected Kupffer cells in the liver and caused a histopathology strikingly similar to mammalian species, this avian Plasmodium species represents an evolutionarily closely related model for studies on the hepatic phase of mammalian malaria.

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Section: Discussionmentioning

confidence: 99%

Exoerythrocytic development of Plasmodium gallinaceum in the White Leghorn chicken

Frevert¹,

Späth²,

Yee³

2008

International Journal for Parasitology

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“…While Toxoplasma has been used to express Plasmodium proteins for the generation of vaccines and the characterization of enzymes , to the best of our knowledge, this is the first report outlining the detailed dissection of the targeting signals of a Plasmodium protein in Toxoplasma . The similarity in the intracellular compartments between the two organisms coupled with the greater clarity in subcellular structure and increased efficiency of transfection makes T. gondii an intermediary in understanding certain aspects of protein trafficking in P. falciparum . This study highlights which of these aspects are suitable for study in Toxoplasma .…”

Section: Discussionmentioning

confidence: 91%

Heterologous expression in Toxoplasma gondii reveals a topogenic signal anchor in a Plasmodium apicoplast protein

et al. 2018

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Glutathione peroxidase‐like thioredoxin peroxidase (Pf TP x Gl ) is an antioxidant enzyme trafficked to the apicoplast, a secondary endosymbiotic organelle, in Plasmodium falciparum . Apicoplast trafficking signals usually consist of N‐terminal signal and transit peptides, but the trafficking signal of Pf TP x Gl appears to exhibit important differences. As transfection is a protracted process in P. falciparum , we expressed the N terminus of Pf TP x Gl as a GFP fusion protein in a related apicomplexan, Toxoplasma gondii , in order to dissect its trafficking signals. We show that Pf TP x Gl possesses an N‐terminal signal anchor that takes the protein to the endoplasmic reticulum in Toxoplasma —this is the first step in the apicoplast targeting pathway. We dissected the residues important for endomembrane system uptake, membrane anchorage, orientation, spacing, and cleavage. Protease protection assays and fluorescence complementation revealed that the C terminus of the protein lies in the ER lumen, a topology that is proposed to be retained in the apicoplast. Additionally, we examined one mutant, responsible for altered Pf TP x Gl targeting in Toxoplasma , in Plasmodium . This study has demonstrated that Pf TP x Gl belongs to an emergent class of proteins that possess signal anchors, unlike the canonical bipartite targeting signals employed for the trafficking of luminal apicoplast proteins. This work adds to the mounting evidence that the signals involved in the targeting of apicoplast membrane proteins may not be as straightforward as those of luminal proteins, and also highlights the usefulness of T. gondii as a heterologous system in certain aspects of this study, such as reducing screening time and facilitating the verification of membrane topology.

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“…Toxoplasma gondii , which is an apicomplexan pathogen responsible for birth defects in humans [45], was the chosen species to illustrate the evaluation methods and to compare the performance of the gene finders. This pathogen was particularly chosen because it is an important model system for the phylum Apicomplexa [46], [47], [48] and has experimentally validated data that can be used for training and testing. All apicomplexans differentiate to forms that invade single or multiple hosts to complete extremely complex life cycles.…”

Section: Introductionmentioning

confidence: 99%

Evaluating High-Throughput Ab Initio Gene Finders to Discover Proteins Encoded in Eukaryotic Pathogen Genomes Missed by Laboratory Techniques

2012

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Next generation sequencing technology is advancing genome sequencing at an unprecedented level. By unravelling the code within a pathogen’s genome, every possible protein (prior to post-translational modifications) can theoretically be discovered, irrespective of life cycle stages and environmental stimuli. Now more than ever there is a great need for high-throughput ab initio gene finding. Ab initio gene finders use statistical models to predict genes and their exon-intron structures from the genome sequence alone. This paper evaluates whether existing ab initio gene finders can effectively predict genes to deduce proteins that have presently missed capture by laboratory techniques. An aim here is to identify possible patterns of prediction inaccuracies for gene finders as a whole irrespective of the target pathogen. All currently available ab initio gene finders are considered in the evaluation but only four fulfil high-throughput capability: AUGUSTUS, GeneMark_hmm, GlimmerHMM, and SNAP. These gene finders require training data specific to a target pathogen and consequently the evaluation results are inextricably linked to the availability and quality of the data. The pathogen, Toxoplasma gondii, is used to illustrate the evaluation methods. The results support current opinion that predicted exons by ab initio gene finders are inaccurate in the absence of experimental evidence. However, the results reveal some patterns of inaccuracy that are common to all gene finders and these inaccuracies may provide a focus area for future gene finder developers.

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Transport and Trafficking: Toxoplasma as a Model for Plasmodium

Cited by 22 publications

References 62 publications

Exoerythrocytic development of Plasmodium gallinaceum in the White Leghorn chicken

Exoerythrocytic development of Plasmodium gallinaceum in the White Leghorn chicken

Heterologous expression in Toxoplasma gondii reveals a topogenic signal anchor in a Plasmodium apicoplast protein

Evaluating High-Throughput Ab Initio Gene Finders to Discover Proteins Encoded in Eukaryotic Pathogen Genomes Missed by Laboratory Techniques

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