Comparative Analysis of Stage Specific Gene Regulation of Apicomplexan Parasites: Plasmodium falciparum and Toxoplasma gondii

AbstractApicomplexan parasites are amongst the most prevalent and morbidity-causing pathogens worldwide. They are responsible for severe diseases in humans and livestock and are thus of great public health and economic importance. Until the sequencing of apicomplexan genomes at the beginning of this century, the occurrence of N- and O-glycoproteins in these parasites was much debated. The synthesis of rudimentary and divergent N-glycans due to lineage-specific gene loss is now well established and has been recently reviewed. Here, we will focus on recent studies that clarified classical O-glycosylation pathways and described new nucleocytosolic glycosylations in Toxoplasma gondii, the causative agents of toxoplasmosis. We will also review the glycosylation of proteins containing thrombospondin type 1 repeats by O-fucosylation and C-mannosylation, newly discovered in Toxoplasma and the malaria parasite Plasmodium falciparum. The functional significance of these post-translational modifications has only started to emerge, but the evidence points towards roles for these protein glycosylation pathways in tissue cyst wall rigidity and persistence in the host, oxygen sensing, and stability of proteins involved in host invasion.

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Comparative Analysis of Apicoplast-Targeted Protein Extension Lengths in Apicomplexan Parasites

BioMed Research International ◽

10.1155/2015/452958 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Alexandr V. Seliverstov ◽

Oleg A. Zverkov ◽

Svetlana N. Istomina ◽

Sergey A. Pirogov ◽

Philip S. Kitsis

Keyword(s):

Plasmodium Falciparum ◽

Comparative Analysis ◽

Protein Translocation ◽

Neospora Caninum ◽

Signal Peptides ◽

Model Species ◽

Apicomplexan Parasites ◽

Important Region ◽

Focus On Results ◽

Species Comparisons

In general, the mechanism of protein translocation through the apicoplast membrane requires a specific extension of a functionally important region of the apicoplast-targeted proteins. The corresponding signal peptides were detected in many apicomplexans but not in the majority of apicoplast-targeted proteins inToxoplasma gondii. InT. gondiisignal peptides are either much diverged or their extension region is processed, which in either case makes the situation different from other studied apicomplexans. We propose a statistic method to compare extensions of the functionally important regions of apicoplast-targeted proteins. More specifically, we provide a comparison of extension lengths of orthologous apicoplast-targeted proteins in apicomplexan parasites. We focus on results obtained for the model speciesT. gondii,Neospora caninum, andPlasmodium falciparum. With our method, cross species comparisons demonstrate that, in average, apicoplast-targeted protein extensions inT. gondiiare 1.5-fold longer than inN. caninumand 2-fold longer than inP. falciparum. Extensions inP. falciparumless than 87 residues in size are longer than the corresponding extensions inN. caninumand, reversely, are shorter if they exceed 88 residues.

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Comparative Analysis of Antisense RNA, Double-Stranded RNA, and Delta Ribozyme-Mediated Gene Regulation in Toxoplasma gondii

Antisense and Nucleic Acid Drug Development ◽

10.1089/108729002320351593 ◽

2002 ◽

Vol 12 (4) ◽

pp. 275-281 ◽

Cited By ~ 24

Author(s):

Fatme Al-Anouti ◽

Sirinart Ananvoranich

Keyword(s):

Gene Regulation ◽

Comparative Analysis ◽

Toxoplasma Gondii ◽

Antisense Rna ◽

Double Stranded Rna ◽

Delta Ribozyme

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Nanoimpact in Plants: Lessons from the Transcriptome

Plants ◽

10.3390/plants10040751 ◽

2021 ◽

Vol 10 (4) ◽

pp. 751

Author(s):

Susana García-Sánchez ◽

Michal Gala ◽

Gabriel Žoldák

Keyword(s):

Gene Regulation ◽

Abiotic Stress ◽

Comparative Analysis ◽

Drought Stress ◽

Stress Responses ◽

Specific Gene ◽

Potential Toxicity ◽

Transcriptional Responses ◽

Regulatory Circuits ◽

Pathogen Response

Transcriptomics studies are available to evaluate the potential toxicity of nanomaterials in plants, and many highlight their effect on stress-responsive genes. However, a comparative analysis of overall expression changes suggests a low impact on the transcriptome. Environmental challenges like pathogens, saline, or drought stress induce stronger transcriptional responses than nanoparticles. Clearly, plants did not have the chance to evolve specific gene regulation in response to novel nanomaterials; but they use common regulatory circuits with other stress responses. A shared effect with abiotic stress is the inhibition of genes for root development and pathogen response. Other works are reviewed here, which also converge on these results.

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A novel heteromeric pantothenate kinase complex in apicomplexan parasites

10.1101/2021.03.16.435557 ◽

2021 ◽

Author(s):

Erick T Tjhin ◽

Vanessa M Howieson ◽

Christina Spry ◽

Giel G van Dooren ◽

Kevin J Saliba

Keyword(s):

Plasmodium Falciparum ◽

Toxoplasma Gondii ◽

Coenzyme A ◽

Functional Protein ◽

Pantothenate Kinase ◽

Apicomplexan Parasites ◽

Single Complex

Coenzyme A is synthesised from pantothenate via five enzyme-mediated steps. The first step is catalysed by pantothenate kinase (PanK). All PanKs characterised to date form homodimers. Many organisms express multiple PanKs. In some cases, these PanKs are not functionally redundant, and some appear to be non-functional. Here, we investigate the PanKs in two pathogenic apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii. Each of these organisms express two PanK homologues (PanK1 and PanK2). We demonstrate that PfPanK1 and PfPanK2 associate, forming a single, functional PanK complex that includes the multi-functional protein, Pf14-3-3I. Similarly, we demonstrate that TgPanK1 and TgPanK2 form a single complex that possesses PanK activity. Both TgPanK1 and TgPanK2 are essential for T. gondii proliferation, specifically due to their PanK activity. Our study constitutes the first examples of heteromeric PanK complexes in nature and provides an explanation for the presence of multiple PanKs within certain organisms.

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Upstream Open Reading Frames (uORFs) in the Apicomplexan Parasites Plasmodium falciparum and Toxoplasma gondii: Small yet Powerful Regulators of Translation

10.20944/preprints202104.0680.v1 ◽

2021 ◽

Author(s):

Chhaminder Kaur ◽

Swati Patankar

Keyword(s):

Gene Expression ◽

Plasmodium Falciparum ◽

Toxoplasma Gondii ◽

Translational Regulation ◽

Life Cycles ◽

Ribosome Profiling ◽

Open Reading Frames ◽

Apicomplexan Parasites ◽

Upstream Open Reading Frames ◽

Reading Frames

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

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Formin-2 drives intracellular polymerisation of actin filaments enabling correct segregation of apicoplasts in Plasmodium falciparum and Toxoplasma gondii

10.1101/488528 ◽

2018 ◽

Cited By ~ 1

Author(s):

Johannes Felix Stortz ◽

Mirko Singer ◽

Jonathan M Wilkes ◽

Markus Meissner ◽

Sujaan Das

Keyword(s):

Plasmodium Falciparum ◽

Toxoplasma Gondii ◽

Gliding Motility ◽

Actin Dynamics ◽

Actin Binding ◽

Comparative Approach ◽

Actin Network ◽

Filamentous Actin ◽

Apicomplexan Parasites

AbstractPathogenic obligate-intracellular apicomplexan parasites possess an essential chloroplast-like organelle called the apicoplast that undergoes division and segregation during replication. Parasite actin is essential during intracellular development, implicated in vesicular transport, parasite replication and apicoplast inheritance. However, the inability to visualise live actin dynamics in apicomplexan parasites limited functional characterisation of both filamentous-actin (F-actin) and actin regulatory factors. Apicomplexans possess at least two distinct formins, Formin-1 and Formin-2, predicted to serve as actin-nucleating factors, and previously implicated in regulating gliding motility and host cell invasion. Here, we expressed chromobodies and validated them as F-actin-binding sensors in Plasmodium falciparum and characterised the in vivo dynamics of the F-actin network. The F-actin network could be modulated chemically and disrupted by conditionally deleting the actin-1 gene. In a comparative approach, we demonstrate that Formin-2 is closely associated with apicoplasts and with the F-actin network in P. falciparum and Toxoplasma gondii. Consequently, disruption of Formin-2 resulted not only in an apicoplast segregation defect, but also in complete abrogation of F-actin dynamics in intracellular parasites. Together, our results strongly indicate that Formin-2-mediated filament formation is the common primary mechanism for F-actin nucleation during apicomplexan intracellular growth effecting apicoplast segregation.

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