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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 -
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 -
Expert Opinion on Therapeutic Targets 2023Toxoplasmosis constitutes a challenge for public health, animal production, and welfare. So far, only a limited panel of drugs has been marketed for clinical... (Review)
Review
INTRODUCTION
Toxoplasmosis constitutes a challenge for public health, animal production, and welfare. So far, only a limited panel of drugs has been marketed for clinical applications. In addition to classical screening, the investigation of unique targets of the parasite may lead to the identification of novel drugs.
AREAS COVERED
Herein, the authors describe the methodology to identify novel drug targets in Toxoplasma gondii and review the literature with a focus on the last two decades.
EXPERT OPINION
Over the last two decades, the investigation of essential proteins of T. gondii as potential drug targets has fostered the hope of identifying novel compounds for the treatment of toxoplasmosis. Despite good efficacies in vitro, only a few classes of these compounds are effective in suitable rodent models, and none has cleared the hurdle to applications in humans. This shows that target-based drug discovery is in no way better than classical screening approaches. In both cases, off-target effects and adverse side effects in the hosts must be considered. Proteomics-driven analyses of parasite- and host-derived proteins that physically bind drug candidates may constitute a suitable tool to characterize drug targets, irrespectively of the drug discovery methods.
Topics: Animals; Humans; Toxoplasmosis; Toxoplasma; Drug Discovery; Drug Delivery Systems
PubMed: 37212443
DOI: 10.1080/14728222.2023.2217353 -
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 -
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 -
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 -
Current Biology : CB Jul 2014Algae frequently get a bad press. Pond slime is a problem in garden pools, algal blooms can produce toxins that incapacitate or kill animals and humans and even the term...
Algae frequently get a bad press. Pond slime is a problem in garden pools, algal blooms can produce toxins that incapacitate or kill animals and humans and even the term seaweed is pejorative - a weed being a plant growing in what humans consider to be the wrong place. Positive aspects of algae are generally less newsworthy - they are the basis of marine food webs, supporting fisheries and charismatic marine megafauna from albatrosses to whales, as well as consuming carbon dioxide and producing oxygen. Here we consider what algae are, their diversity in terms of evolutionary origin, size, shape and life cycles, and their role in the natural environment and in human affairs.
Topics: Apicomplexa; Biodiversity; Charophyceae; Chlorophyta; Cryptophyta; Cyanobacteria; Dinoflagellida; Eukaryota; Glaucophyta; Haptophyta; Reproduction; Rhizaria; Rhodophyta; Stramenopiles; Symbiosis
PubMed: 25004359
DOI: 10.1016/j.cub.2014.05.039 -
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 -
Genes May 2022Transposable elements (TEs) are mobile genetic elements found in the majority of eukaryotic genomes. Genomic studies of protozoan parasites from the phylum Apicomplexa...
Transposable elements (TEs) are mobile genetic elements found in the majority of eukaryotic genomes. Genomic studies of protozoan parasites from the phylum Apicomplexa have only reported a handful of TEs in some species and a complete absence in others. Here, we studied sixty-four Apicomplexa genomes available in public databases, using a 'de novo' approach to build candidate TE models and multiple strategies from known TE sequence databases, pattern recognition of TEs, and protein domain databases, to identify possible TEs. We offer an insight into the distribution and the type of TEs that are present in these genomes, aiming to shed some light on the process of gains and losses of TEs in this phylum. We found that TEs comprise a very small portion in these genomes compared to other organisms, and in many cases, there are no apparent traces of TEs. We were able to build and classify 151 models from the TE consensus sequences obtained with RepeatModeler, 96 LTR TEs with LTRpred, and 44 LINE TEs with MGEScan. We found LTR Gypsy-like TEs in Eimeria, Gregarines, Haemoproteus, and Plasmodium genera. Additionally, we described LINE-like TEs in some species from the genera Babesia and Theileria. Finally, we confirmed the absence of TEs in the genus Cryptosporidium. Interestingly, Apicomplexa seem to be devoid of Class II transposons.
Topics: Animals; Apicomplexa; Cryptosporidiosis; Cryptosporidium; DNA Transposable Elements; Evolution, Molecular; Parasites
PubMed: 35627271
DOI: 10.3390/genes13050887 -
Trends in Parasitology Oct 2020Recent breakthroughs in high-throughput technologies, transcriptomics, and advances in our understanding of gene regulatory networks have enhanced our perspective on the... (Review)
Review
Recent breakthroughs in high-throughput technologies, transcriptomics, and advances in our understanding of gene regulatory networks have enhanced our perspective on the complex interplay between parasite and host. Noncoding RNA molecules have been implicated in critical roles covering a broad range of biological processes in the Apicomplexa. Processes that are affected range from parasite development to host-parasite interactions and include interactions with epigenetic machinery and other regulatory factors. Here we review recent progress involving noncoding RNAs and their functions in the Apicomplexa, with a focus on three parasites: Plasmodium, Toxoplasma, and Cryptosporidium. We discuss the limitations and challenges of current methods applied to apicomplexan noncoding RNA study and discuss future directions in this exciting field.
Topics: Apicomplexa; Epigenesis, Genetic; Host-Parasite Interactions; RNA, Untranslated; Research
PubMed: 32828659
DOI: 10.1016/j.pt.2020.07.006