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Cell Host & Microbe Nov 2020Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These...
Apicomplexan parasites cause major human disease and food insecurity. They owe their considerable success to highly specialized cell compartments and structures. These adaptations drive their recognition, nondestructive penetration, and elaborate reengineering of the host's cells to promote their growth, dissemination, and the countering of host defenses. The evolution of unique apicomplexan cellular compartments is concomitant with vast proteomic novelty. Consequently, half of apicomplexan proteins are unique and uncharacterized. Here, we determine the steady-state subcellular location of thousands of proteins simultaneously within the globally prevalent apicomplexan parasite Toxoplasma gondii. This provides unprecedented comprehensive molecular definition of these unicellular eukaryotes and their specialized compartments, and these data reveal the spatial organizations of protein expression and function, adaptation to hosts, and the underlying evolutionary trajectories of these pathogens.
Topics: Apicomplexa; Biological Evolution; Epitopes; Host-Pathogen Interactions; Humans; Proteome; Proteomics; Protozoan Proteins; Toxoplasma
PubMed: 33053376
DOI: 10.1016/j.chom.2020.09.011 -
Trends in Parasitology May 2024The micropore, a mysterious structure found in apicomplexan species, was recently shown to be essential for nutrient acquisition in Plasmodium falciparum and Toxoplasma... (Review)
Review
The micropore, a mysterious structure found in apicomplexan species, was recently shown to be essential for nutrient acquisition in Plasmodium falciparum and Toxoplasma gondii. However, the differences between the micropores of these two parasites questions the nature of a general apicomplexan micropore structure and whether the formation process model from Plasmodium can be applied to other apicomplexans. We analyzed the literature on different apicomplexan micropores and found that T. gondii probably harbors a more representative micropore type than the more widely studied ones in Plasmodium. Using recent knowledge of the Kelch 13 (K13) protein interactome and gene depletion phenotypes in the T. gondii micropore, we propose a model of micropore formation, thus enriching our wider understanding of micropore protein function.
Topics: Apicomplexa; Toxoplasma; Plasmodium falciparum; Protozoan Proteins
PubMed: 38637184
DOI: 10.1016/j.pt.2024.03.008 -
Cell Host & Microbe Apr 2023Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively...
Cryptosporidium is a leading cause of diarrheal disease in children and an important contributor to early childhood mortality. The parasite invades and extensively remodels intestinal epithelial cells, building an elaborate interface structure. How this occurs at the molecular level and the contributing parasite factors are largely unknown. Here, we generated a whole-cell spatial proteome of the Cryptosporidium sporozoite and used genetic and cell biological experimentation to discover the Cryptosporidium-secreted effector proteome. These findings reveal multiple organelles, including an original secretory organelle, and generate numerous compartment markers by tagging native gene loci. We show that secreted proteins are delivered to the parasite-host interface, where they assemble into different structures including a ring that anchors the parasite into its unique epicellular niche. Cryptosporidium thus uses a complex set of secretion systems during and following invasion that act in concert to subjugate its host cell.
Topics: Child, Preschool; Child; Humans; Cryptosporidium; Proteome; Cryptosporidiosis; Organelles; Cryptosporidium parvum; Protozoan Proteins; Host-Parasite Interactions
PubMed: 36958336
DOI: 10.1016/j.chom.2023.03.001 -
Trends in Parasitology Oct 2023Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites... (Review)
Review
Meiosis is sexual cell division, a process in eukaryotes whereby haploid gametes are produced. Compared to canonical model eukaryotes, meiosis in apicomplexan parasites appears to diverge from the process with respect to the molecular mechanisms involved; the biology of Plasmodium meiosis, and its regulation by means of post-translational modification, are largely unexplored. Here, we discuss the impact of technological advances in cell biology, evolutionary bioinformatics, and genome-wide functional studies on our understanding of meiosis in the Apicomplexa. These parasites, including Plasmodium falciparum, Toxoplasma gondii, and Eimeria spp., have significant socioeconomic impact on human and animal health. Understanding this key stage during the parasite's life cycle may well reveal attractive targets for therapeutic intervention.
Topics: Animals; Humans; Plasmodium; Eukaryota; Plasmodium falciparum; Meiosis; Toxoplasma
PubMed: 37541799
DOI: 10.1016/j.pt.2023.07.002 -
Trends in Parasitology Apr 2021
Topics: Animals; Culicidae; Malaria, Avian; Mosquito Vectors; Plasmodium
PubMed: 32660871
DOI: 10.1016/j.pt.2020.06.004 -
Molecular Microbiology Apr 2024Apicomplexan parasites comprise significant pathogens of humans, livestock and wildlife, but also represent a diverse group of eukaryotes with interesting and unique... (Review)
Review
Apicomplexan parasites comprise significant pathogens of humans, livestock and wildlife, but also represent a diverse group of eukaryotes with interesting and unique cell biology. The study of cell biology in apicomplexan parasites is complicated by their small size, and historically this has required the application of cutting-edge microscopy techniques to investigate fundamental processes like mitosis or cell division in these organisms. Recently, a technique called expansion microscopy has been developed, which rather than increasing instrument resolution like most imaging modalities, physically expands a biological sample. In only a few years since its development, a derivative of expansion microscopy known as ultrastructure-expansion microscopy (U-ExM) has been widely adopted and proven extremely useful for studying cell biology of Apicomplexa. Here, we review the insights into apicomplexan cell biology that have been enabled through the use of U-ExM, with a specific focus on Plasmodium, Toxoplasma and Cryptosporidium. Further, we summarize emerging expansion microscopy modifications and modalities and forecast how these may influence the field of parasite cell biology in future.
Topics: Animals; Humans; Parasites; Microscopy; Cryptosporidium; Cryptosporidiosis; Toxoplasma; Mitosis
PubMed: 37571814
DOI: 10.1111/mmi.15135 -
Parasites & Vectors Jan 2022Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are... (Review)
Review
Apicomplexans are important pathogens that cause severe infections in humans and animals. The biology and pathogeneses of these parasites have shown that proteins are intrinsically modulated during developmental transitions, physiological processes and disease progression. Also, proteins are integral components of parasite structural elements and organelles. Among apicomplexan parasites, Eimeria species are an important disease aetiology for economically important animals wherein identification and characterisation of proteins have been long-winded. Nonetheless, this review seeks to give a comprehensive overview of constitutively expressed Eimeria proteins. These molecules are discussed across developmental stages, organelles and sub-cellular components vis-à-vis their biological functions. In addition, hindsight and suggestions are offered with intention to summarise the existing trend of eimerian protein characterisation and to provide a baseline for future studies.
Topics: Animals; Antigens, Protozoan; Apicomplexa; Bodily Secretions; Chickens; Coccidiosis; Eimeria; Eimeria tenella; Genes, Protozoan; Host-Parasite Interactions; Humans; Membrane Proteins; Merozoites; Oocysts; Organelles; Peptide Hydrolases; Poultry Diseases; Protein Transport; Sporozoites
PubMed: 35073987
DOI: 10.1186/s13071-022-05159-0 -
MBio Feb 2019Alternative splicing is a widespread, essential, and complex component of gene regulation. Apicomplexan parasites have long been recognized to produce alternatively... (Review)
Review
Alternative splicing is a widespread, essential, and complex component of gene regulation. Apicomplexan parasites have long been recognized to produce alternatively spliced transcripts for some genes and can produce multiple protein products that are essential for parasite growth. Recent approaches are now providing more wide-ranging surveys of the extent of alternative splicing; some indicate that alternative splicing is less widespread than in other model eukaryotes, whereas others suggest levels comparable to those of previously studied groups. In many cases, apicomplexan alternative splicing events appear not to generate multiple alternative proteins but instead produce aberrant or noncoding transcripts. Nonetheless, appropriate regulation of alternative splicing is clearly essential in and parasites, suggesting a biological role for at least some of the alternative splicing observed. Several studies have now disrupted conserved regulators of alternative splicing and demonstrated lethal effects in apicomplexans. This minireview discusses methods to accurately determine the extent of alternative splicing in Apicomplexa and discuss potential biological roles for this conserved process in a phylum of parasites with compact genomes.
Topics: Alternative Splicing; Animals; Apicomplexa; Gene Expression Regulation; Parasites
PubMed: 30782661
DOI: 10.1128/mBio.02866-18 -
Advances in Experimental Medicine and... 2020The phylum of Apicomplexa groups obligate intracellular parasites that exhibit unique classes of unconventional myosin motors. These parasites also encode a limited... (Review)
Review
The phylum of Apicomplexa groups obligate intracellular parasites that exhibit unique classes of unconventional myosin motors. These parasites also encode a limited repertoire of actins, actin-like proteins, actin-binding proteins and nucleators of filamentous actin (F-actin) that display atypical properties. In the last decade, significant progress has been made to visualize F-actin and to unravel the functional contribution of actomyosin systems in the biology of Toxoplasma and Plasmodium, the most genetically-tractable members of the phylum. In addition to assigning specific roles to each myosin, recent biochemical and structural studies have begun to uncover mechanistic insights into myosin function at the atomic level. In several instances, the myosin light chains associated with the myosin heavy chains have been identified, helping to understand the composition of the motor complexes and their mode of regulation. Moreover, the considerable advance in proteomic methodologies and especially in assignment of posttranslational modifications is offering a new dimension to our understanding of the regulation of actin dynamics and myosin function. Remarkably, the actomyosin system contributes to three major processes in Toxoplasma gondii: (i) organelle trafficking, positioning and inheritance, (ii) basal pole constriction and intravacuolar cell-cell communication and (iii) motility, invasion, and egress from infected cells. In this chapter, we summarize how the actomyosin system harnesses these key events to ensure successful completion of the parasite life cycle.
Topics: Actins; Actomyosin; Animals; Plasmodium; Proteomics; Protozoan Proteins; Toxoplasma
PubMed: 32451865
DOI: 10.1007/978-3-030-38062-5_14 -
Critical Reviews in Biochemistry and... Jun 2017The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of... (Review)
Review
The increasing prevalence of infections involving intracellular apicomplexan parasites such as Plasmodium, Toxoplasma, and Cryptosporidium (the causative agents of malaria, toxoplasmosis, and cryptosporidiosis, respectively) represent a significant global healthcare burden. Despite their significance, few treatments are available; a situation that is likely to deteriorate with the emergence of new resistant strains of parasites. To lay the foundation for programs of drug discovery and vaccine development, genome sequences for many of these organisms have been generated, together with large-scale expression and proteomic datasets. Comparative analyses of these datasets are beginning to identify the molecular innovations supporting both conserved processes mediating fundamental roles in parasite survival and persistence, as well as lineage-specific adaptations associated with divergent life-cycle strategies. The challenge is how best to exploit these data to derive insights into parasite virulence and identify those genes representing the most amenable targets. In this review, we outline genomic datasets currently available for apicomplexans and discuss biological insights that have emerged as a consequence of their analysis. Of particular interest are systems-based resources, focusing on areas of metabolism and host invasion that are opening up opportunities for discovering new therapeutic targets.
Topics: Animals; Apicomplexa; Gene Expression Regulation; Genome, Protozoan; Humans; Life Cycle Stages; Proteomics; Protozoan Proteins
PubMed: 28276701
DOI: 10.1080/10409238.2017.1290043