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Molecular Microbiology Mar 2021Rhoptries are specialized secretory organelles found in the Apicomplexa phylum, playing a central role in the establishment of parasitism. The rhoptry content includes... (Review)
Review
Rhoptries are specialized secretory organelles found in the Apicomplexa phylum, playing a central role in the establishment of parasitism. The rhoptry content includes membranous as well as proteinaceous materials that are discharged into the host cell in a regulated fashion during parasite entry. A set of rhoptry neck proteins form a RON complex that critically participates in the moving junction formation during invasion. Some of the rhoptry bulb proteins are associated with the membranous materials and contribute to the formation of the parasitophorous vacuole membrane while others are targeted into the host cell including the nucleus to subvert cellular functions. Here, we review the recent studies on Toxoplasma and Plasmodium parasites that shed light on the key steps leading to rhoptry biogenesis, trafficking, and discharge.
Topics: Animals; Host-Parasite Interactions; Humans; Malaria; Organelle Biogenesis; Organelles; Plasmodium; Protein Transport; Protozoan Proteins; Toxoplasma; Toxoplasmosis; Virulence
PubMed: 33368727
DOI: 10.1111/mmi.14674 -
Frontiers in Cellular and Infection... 2022In the age of big data an important question is how to ensure we make the most out of the resources we generate. In this review, we discuss the major methods used in... (Review)
Review
In the age of big data an important question is how to ensure we make the most out of the resources we generate. In this review, we discuss the major methods used in Apicomplexan and Kinetoplastid research to produce big datasets and advance our understanding of and biology. We debate the benefits and limitations of the current technologies, and propose future advancements that may be key to improving our use of these techniques. Finally, we consider the difficulties the field faces when trying to make the most of the abundance of data that has already been, and will continue to be, generated.
Topics: Big Data; Cryptosporidiosis; Cryptosporidium; Humans; Plasmodium; Toxoplasma
PubMed: 35734575
DOI: 10.3389/fcimb.2022.900878 -
International Journal For Parasitology Oct 2017Apicomplexan parasites such as Babesia, Theileria, Eimeria, Cryptosporidium and Toxoplasma greatly impact animal health globally, and improved, cost-effective measures... (Review)
Review
Apicomplexan parasites such as Babesia, Theileria, Eimeria, Cryptosporidium and Toxoplasma greatly impact animal health globally, and improved, cost-effective measures to control them are urgently required. These parasites have complex multi-stage life cycles including obligate intracellular stages. Major gaps in our understanding of the biology of these relatively poorly characterised parasites and the diseases they cause severely limit options for designing novel control methods. Here we review potentially important shared aspects of the biology of these parasites, such as cell invasion, host cell modification, and asexual and sexual reproduction, and explore the potential of the application of relatively well-established or newly emerging genetic manipulation methods, such as classical transfection or gene editing, respectively, for closing important gaps in our knowledge of the function of specific genes and proteins, and the biology of these parasites. In addition, genetic manipulation methods impact the development of novel methods of control of the diseases caused by these economically important parasites. Transient and stable transfection methods, in conjunction with whole and deep genome sequencing, were initially instrumental in improving our understanding of the molecular biology of apicomplexan parasites and paved the way for the application of the more recently developed gene editing methods. The increasingly efficient and more recently developed gene editing methods, in particular those based on the CRISPR/Cas9 system and previous conceptually similar techniques, are already contributing to additional gene function discovery using reverse genetics and related approaches. However, gene editing methods are only possible due to the increasing availability of in vitro culture, transfection, and genome sequencing and analysis techniques. We envisage that rapid progress in the development of novel gene editing techniques applied to apicomplexan parasites of veterinary interest will ultimately lead to the development of novel and more efficient methods for disease control.
Topics: Animals; Apicomplexa; CRISPR-Cas Systems; DNA Repair; Deoxyribonucleases; Gene Editing; Gene Knockout Techniques; Genome, Protozoan; Life Cycle Stages; Mutagenesis, Insertional; Protozoan Infections, Animal; Protozoan Vaccines; Transfection; Virulence Factors
PubMed: 28893636
DOI: 10.1016/j.ijpara.2017.08.002 -
Molecular Microbiology Jan 2018Parasites of the Apicomplexa phylum, such as Plasmodium spp. and Toxoplasma gondii, undergo complex life cycles involving multiple stages with distinct biology and... (Review)
Review
Parasites of the Apicomplexa phylum, such as Plasmodium spp. and Toxoplasma gondii, undergo complex life cycles involving multiple stages with distinct biology and morphologies. Post-translational modifications (PTMs), such as phosphorylation, acetylation and glycosylation, regulate numerous cellular processes, playing a role in every aspect of cell biology. PTMs can occur on proteins at any time in their lifespan and through alterations of target protein activity, localization, protein-protein interactions, among other functions, dramatically increase proteome diversity and complexity. In addition, PTMs can be induced or removed on changes in cellular environment and state. Thus, PTMs are likely to be key regulators of developmental transitions, biology and pathogenesis of apicomplexan parasites. In this review we examine the roles of PTMs in both parasite-specific and conserved eukaryotic processes, and the potential crosstalk between PTMs, that together regulate the intricate lives of these protozoa.
Topics: Acetylation; Amino Acid Sequence; Animals; Apicomplexa; Eukaryota; Glycosylation; Humans; Phosphorylation; Protein Processing, Post-Translational; Proteome; Proteomics; Protozoan Proteins; Toxoplasma
PubMed: 29052917
DOI: 10.1111/mmi.13867 -
Current Issues in Molecular Biology 2012Malaria is caused by species in the apicomplexan genus Plasmodium, which infect hundreds of millions of people each year and kill close to one million. While malaria is... (Review)
Review
Malaria is caused by species in the apicomplexan genus Plasmodium, which infect hundreds of millions of people each year and kill close to one million. While malaria is the most notorious of the apicomplexan-caused diseases, other members of eukaryotic phylum Apicomplexa are responsible for additional, albeit less well-known, diseases in humans, economically important livestock, and a variety of other vertebrates. Diseases such as babesiosis (hemolytic anemia), theileriosis and East Coast Fever, cryptosporidiosis, and toxoplasmosis are caused by the apicomplexans Babesia, Theileria, Cryptosporidium and Toxoplasma, respectively. In addition to the loss of human life, these diseases are responsible for losses of billions of dollars annually. Hence, the research into new drug targets remains a high priority. Ribonucleotide reductase (RNR) is an essential enzyme found in all domains of life. It is the only means by which de novo synthesis of deoxyribonucleotides occurs, without which DNA replication and repair cannot proceed. RNR has long been the target of antiviral, antibacterial and anti-cancer therapeutics. Herein, we review the chemotherapeutic methods used to inhibit RNR, with particular emphasis on the role of RNR inhibition in Apicomplexa, and in light of the novel RNR R2_e2 subunit recently identified in apicomplexan parasites.
Topics: Amino Acid Sequence; Animals; Antiprotozoal Agents; Apicomplexa; Humans; Molecular Sequence Data; Molecular Targeted Therapy; Parasites; Protozoan Infections; Ribonucleotide Reductases
PubMed: 21791713
DOI: No ID Found -
Microbes and Infection Aug 2012Protein phosphorylation plays a fundamental role in the biology of apicomplexan parasites. Many apicomplexan protein kinases are substantially different from their... (Comparative Study)
Comparative Study Review
Protein phosphorylation plays a fundamental role in the biology of apicomplexan parasites. Many apicomplexan protein kinases are substantially different from their mammalian orthologues, and thus constitute a landscape of potential drug targets. Here, we integrate genomic, biochemical, genetic and evolutionary information to provide an integrated and up-to-date analysis of twelve apicomplexan kinomes. All kinome sequences are available through the Kinomer database.
Topics: Apicomplexa; Protein Kinases
PubMed: 22587893
DOI: 10.1016/j.micinf.2012.04.007 -
Nucleic Acids Research Jan 2011Full-Parasites (http://fullmal.hgc.jp/) is a transcriptome database of apicomplexa parasites, which include Plasmodium and Toxoplasma species. The latest version of...
Full-Parasites (http://fullmal.hgc.jp/) is a transcriptome database of apicomplexa parasites, which include Plasmodium and Toxoplasma species. The latest version of Full-Parasites contains a total of 105,786 EST sequences from 12 parasites, of which 5925 full-length cDNAs have been completely sequenced. Full-Parasites also contain more than 30 million transcription start sites (TSS) for Plasmodium falciparum (Pf) and Toxoplasma gondii (Tg), which were identified using our novel oligo-capping-based protocol. Various types of cDNA data resources were interconnected with our original database functionalities. Specifically, in this update, we have included two unique RNA-Seq data sets consisting of 730 million mapped RNA-Seq tags. One is a dataset of 16 time-lapse experiments of cultured bradyzoite differentiation for Tg. The other dataset includes 31 clinical samples of Pf. Parasite RNA was extracted together with host human RNA, and the extracted mixed RNA was used for RNA sequencing, with the expectation that gene expression information from the host and parasite would be simultaneously represented. By providing the largest unique full-length cDNA and dynamic transcriptome data, Full-Parasites is useful for understanding host-parasite interactions and will help to eventually elucidate how monophyletic organisms have evolved to become parasites by adopting complex life cycles.
Topics: Apicomplexa; DNA, Complementary; Databases, Nucleic Acid; Expressed Sequence Tags; Gene Expression Profiling; Host-Parasite Interactions; Humans; Plasmodium falciparum; RNA, Protozoan; Sequence Analysis, RNA; Toxoplasma; Transcription Initiation Site
PubMed: 21051343
DOI: 10.1093/nar/gkq1111 -
Current Opinion in Biotechnology Oct 2010Apicomplexan parasites utilize a unique form of 'gliding motility' to traverse across substrates, migrate through tissues, and invade into and finally egress from their... (Review)
Review
Apicomplexan parasites utilize a unique form of 'gliding motility' to traverse across substrates, migrate through tissues, and invade into and finally egress from their vertebrate host cells. Parasite gliding relies on the treadmilling of surface adhesins linked to short actin filaments that are translocated rearward by stationary small myosin motors. New details reveal mechanistic insight into the coordinated release and processing of adhesins, the complexity of adhesin-substrate interactions, the regulation of the actin-myosin motor complex, and the formation of a novel junction at the host-parasite interface. These activities are carefully orchestrated to provide an efficient process for motility that is essential for parasite survival. The parasite-specific nature of many of these steps reveals several essential points that may be targeted for intervention.
Topics: Actins; Animals; Apicomplexa; Host-Parasite Interactions; Humans; Myosins; Protozoan Proteins
PubMed: 20580218
DOI: 10.1016/j.copbio.2010.05.009 -
FEMS Microbiology Reviews Jul 2013Rhoptries are club-shaped secretory organelles located at the anterior pole of species belonging to the phylum of Apicomplexa. Parasites of this phylum are responsible... (Review)
Review
Rhoptries are club-shaped secretory organelles located at the anterior pole of species belonging to the phylum of Apicomplexa. Parasites of this phylum are responsible for a huge burden of disease in humans and animals and a loss of economic productivity. Members of this elite group of obligate intracellular parasites include Plasmodium spp. that cause malaria and Cryptosporidium spp. that cause diarrhoeal disease. Although rhoptries are almost ubiquitous throughout the phylum, the relevance and role of the proteins contained within the rhoptries varies. Rhoptry contents separate into two intra-organellar compartments, the neck and the bulb. A number of rhoptry neck proteins are conserved between species and are involved in functions such as host cell invasion. The bulb proteins are less well-conserved and probably evolved for a particular lifestyle. In the majority of species studied to date, rhoptry content is involved in formation and maintenance of the parasitophorous vacuole; however some species live free within the host cytoplasm. In this review, we will summarise the knowledge available regarding rhoptry proteins. Specifically, we will discuss the role of the rhoptry kinases that are used by Toxoplasma gondii and other coccidian parasites to subvert the host cellular functions and prevent parasite death.
Topics: Animals; Apicomplexa; Host-Parasite Interactions; Humans; Protozoan Infections
PubMed: 23186105
DOI: 10.1111/1574-6976.12013 -
Journal of Structural Biology May 2015The apicomplexan family of pathogens, which includes Plasmodium spp. and Toxoplasma gondii, are primarily obligate intracellular parasites and invade multiple cell... (Review)
Review
The apicomplexan family of pathogens, which includes Plasmodium spp. and Toxoplasma gondii, are primarily obligate intracellular parasites and invade multiple cell types. These parasites express extracellular membrane protein receptors, adhesins, to form specific pathogen-host cell interaction complexes. Various adhesins are used to invade a variety of cell types. The receptors are linked to an actomyosin motor, which is part of a complex comprised of many proteins known as the invasion machinery or glideosome. To date, reviews on invasion have focused primarily on the molecular pathways and signals of invasion, with little or no structural information presented. Over 75 structures of parasite receptors and glideosome proteins have been deposited with the Protein Data Bank. These structures include adhesins, motor proteins, bridging proteins, inner membrane complex and cytoskeletal proteins, as well as co-crystal structures with peptides and antibodies. These structures provide information regarding key interactions necessary for target receptor engagement, machinery complex formation, how force is transmitted, and the basis of inhibitory antibodies. Additionally, these structures can provide starting points for the development of antibodies and inhibitory molecules targeting protein-protein interactions, with the aim to inhibit invasion. This review provides an overview of the parasite adhesin protein families, the glideosome components, glideosome architecture, and discuss recent work regarding alternative models.
Topics: Actomyosin; Apicomplexa; Databases, Protein; Host-Pathogen Interactions; Membrane Proteins; Models, Molecular; Multiprotein Complexes; Protein Binding; Protein Conformation; Protein Interaction Mapping; Protein Structure, Tertiary
PubMed: 25764948
DOI: 10.1016/j.jsb.2015.02.008