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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 -
The FEBS Journal Jan 2021The Apicomplexa phylum groups important human and animal pathogens that cause severe diseases, encompassing malaria, toxoplasmosis, and cryptosporidiosis. In common with... (Review)
Review
The Apicomplexa phylum groups important human and animal pathogens that cause severe diseases, encompassing malaria, toxoplasmosis, and cryptosporidiosis. In common with most organisms, apicomplexans rely on heme as cofactor for several enzymes, including cytochromes of the electron transport chain. This heme derives from de novo synthesis and/or the development of uptake mechanisms to scavenge heme from their host. Recent studies have revealed that heme synthesis is essential for Toxoplasma gondii tachyzoites, as well as for the mosquito and liver stages of Plasmodium spp. In contrast, the erythrocytic stages of the malaria parasites rely on scavenging heme from the host red blood cell. The unusual heme synthesis pathway in Apicomplexa spans three cellular compartments and comprises enzymes of distinct ancestral origin, providing promising drug targets. Remarkably given the requirement for heme, T. gondii can tolerate the loss of several heme synthesis enzymes at a high fitness cost, while the ferrochelatase is essential for survival. These findings indicate that T. gondii is capable of salvaging heme precursors from its host. Furthermore, heme is implicated in the activation of the key antimalarial drug artemisinin. Recent findings established that a reduction in heme availability corresponds to decreased sensitivity to artemisinin in T. gondii and Plasmodium falciparum, providing insights into the possible development of combination therapies to tackle apicomplexan parasites. This review describes the microeconomics of heme in Apicomplexa, from supply, either from de novo synthesis or scavenging, to demand by metabolic pathways, including the electron transport chain.
Topics: Animals; Anti-Infective Agents; Artemisinins; Cryptosporidium; Cytochromes; Erythrocytes; Ferrochelatase; Gene Expression; Heme; Host-Pathogen Interactions; Humans; Life Cycle Stages; Metabolic Networks and Pathways; Plasmodium berghei; Plasmodium falciparum; Protozoan Proteins; Toxoplasma
PubMed: 32530125
DOI: 10.1111/febs.15445 -
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 -
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 -
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 -
PLoS Pathogens Mar 2022Apicomplexa are obligate intracellular parasites responsible for major human infectious diseases such as toxoplasmosis and malaria, which pose social and economic... (Review)
Review
Apicomplexa are obligate intracellular parasites responsible for major human infectious diseases such as toxoplasmosis and malaria, which pose social and economic burdens around the world. To survive and propagate, these parasites need to acquire a significant number of essential biomolecules from their hosts. Among these biomolecules, lipids are a key metabolite required for parasite membrane biogenesis, signaling events, and energy storage. Parasites can either scavenge lipids from their host or synthesize them de novo in a relict plastid, the apicoplast. During their complex life cycle (sexual/asexual/dormant), Apicomplexa infect a large variety of cells and their metabolic flexibility allows them to adapt to different host environments such as low/high fat content or low/high sugar levels. In this review, we discuss the role of lipids in Apicomplexa parasites and summarize recent findings on the metabolic mechanisms in host nutrient adaptation.
Topics: Animals; Apicomplexa; Apicoplasts; Humans; Lipid Metabolism; Lipids; Parasites
PubMed: 35298557
DOI: 10.1371/journal.ppat.1010313 -
Trends in Parasitology Apr 2021Genome-scale mutagenesis screens for genes essential for apicomplexan parasite survival have been completed in three species: Plasmodium falciparum, the major human... (Review)
Review
Genome-scale mutagenesis screens for genes essential for apicomplexan parasite survival have been completed in three species: Plasmodium falciparum, the major human malaria parasite, Plasmodium berghei, a model rodent malaria parasite, and the more distantly related Toxoplasma gondii, the causative agent of toxoplasmosis. These three species share 2606 single-copy orthologs, 1500 of which have essentiality data in all three screens. In this review, we explore the overlap between these datasets to define the core essential genes of the phylum Apicomplexa. We further discuss the implications of these groundbreaking studies for understanding apicomplexan parasite biology, and we identify promising areas of focus for developing new pan-apicomplexan parasite interventions.
Topics: Apicomplexa; Genes, Essential; Genome, Protozoan
PubMed: 33419671
DOI: 10.1016/j.pt.2020.11.007 -
Trends in Parasitology Sep 2019Gregarine apicomplexans are closely related to parasites such as Plasmodium, Toxoplasma, and Cryptosporidium, which are causing severe health and economic burdens.... (Review)
Review
Gregarine apicomplexans are closely related to parasites such as Plasmodium, Toxoplasma, and Cryptosporidium, which are causing severe health and economic burdens. Colonizing only invertebrates and having no obvious medical relevance, they are mostly ignored in 'omics' studies, although gregarines are the most basal apicomplexans and therefore key players in the understanding of the evolution of parasitism in the Apicomplexa from free-living ancestors. They belong to the largest exclusively parasitic phylum, but is this perception actually true? The effects of gregarines on their hosts seem to cover the whole spectrum of symbiosis from mutualistic to parasitic. We suggest future research directions to understand the evolutionary role of gregarines, by elucidating their biology and interaction with their hosts and the hosts' microbiota.
Topics: Animals; Apicomplexa; Biological Evolution; Invertebrates; Symbiosis
PubMed: 31345767
DOI: 10.1016/j.pt.2019.06.013 -
Molecular and Biochemical Parasitology 2016Many members of the Apicomplexa contain a remnant chloroplast, known as an apicoplast. The apicoplast encodes numerous genes, and loss of the organelle is lethal. Here,... (Review)
Review
Many members of the Apicomplexa contain a remnant chloroplast, known as an apicoplast. The apicoplast encodes numerous genes, and loss of the organelle is lethal. Here, we present a summary of what is known about apicoplast transcription. Unlike plant chloroplasts, there is a single RNA polymerase, and initial transcription is polycistronic. RNA is then cleaved into tRNA, mRNA and rRNA molecules. Significant levels of antisense transcription have been reported, together with a single case of RNA editing. Polycistronic transcription is also observed in the related algae Chromera and Vitrella, which retain a photosynthetic chloroplast. Surprisingly, a polyU tail is added to Chromera and Vitrella transcripts which encode proteins involved in photosynthesis. No such tail is added to Plasmodium transcripts. Transcription in the Apicomplexa is remarkably similar to that seen in the chloroplast of the related peridinin dinoflagellate algae, reflecting the common evolutionary origins of the organelle.
Topics: Apicomplexa; Apicoplasts; DNA-Directed RNA Polymerases; Dinoflagellida; Gene Expression Regulation; Genes, Protozoan; Genome; RNA Editing; RNA Processing, Post-Transcriptional; Transcription, Genetic
PubMed: 27485555
DOI: 10.1016/j.molbiopara.2016.07.004