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Frontiers in Cellular and Infection... 2021
Topics: Animals; Parasites; Toxoplasma
PubMed: 33937107
DOI: 10.3389/fcimb.2021.680184 -
Trends in Parasitology Jul 2021Apicomplexan parasites are unicellular eukaryotes that invade the cells in which they proliferate. The development of genetic tools in Toxoplasma, and then in... (Review)
Review
Apicomplexan parasites are unicellular eukaryotes that invade the cells in which they proliferate. The development of genetic tools in Toxoplasma, and then in Plasmodium, in the 1990s allowed the first description of the molecular machinery used for motility and invasion, revealing a crucial role for two different secretory organelles, micronemes and rhoptries. Rhoptry proteins are injected directly into the host cytoplasm not only to promote invasion but also to manipulate host functions. Nonetheless, the injection machinery has remained mysterious, a major conundrum in the field. Here we review recent progress in uncovering structural components and proteins implicated in rhoptry exocytosis and explain how revisiting early findings and considering the evolutionary origins of Apicomplexa contributed to some of these discoveries.
Topics: Animals; Apicomplexa; Cells; Exocytosis; Host-Parasite Interactions; Humans; Organelles; Protozoan Proteins
PubMed: 34045149
DOI: 10.1016/j.pt.2021.04.011 -
Current Opinion in Microbiology Dec 2022Members of the Apicomplexa phylum are unified by an apical complex tailored for motility and host cell invasion. It includes regulated secretory organelles and a conoid... (Review)
Review
Members of the Apicomplexa phylum are unified by an apical complex tailored for motility and host cell invasion. It includes regulated secretory organelles and a conoid attached to the apical polar ring (APR) from which subpellicular microtubules emerge. In coccidia, the conoid is composed of a cone of spiraling tubulin fibers, two preconoidal rings, and two intraconoidal microtubules. The conoid extrudes through the APR in motile parasites. Recent advances in proteomics, cryo-electron tomography, super-resolution, and expansion microscopy provide a more comprehensive view of the spatial and temporal resolution of proteins belonging to the conoid subcomponents. In combination with the phenotyping of targeted mutants, the biogenesis, turnover, dynamics, and function of the conoid begin to be elucidated.
Topics: Toxoplasma; Apicomplexa; Cytoskeleton; Microtubules; Organelles
PubMed: 36332501
DOI: 10.1016/j.mib.2022.102226 -
Current Opinion in Microbiology Aug 2015Pore-forming proteins (PFPs) encompass a broad family of proteins that are used for virulence or immune defense. Members of the cholesterol-dependent cytolysins (CDCs)... (Review)
Review
Pore-forming proteins (PFPs) encompass a broad family of proteins that are used for virulence or immune defense. Members of the cholesterol-dependent cytolysins (CDCs) and membrane attack complex/perforin (MACPF) family of PFPs form large β-barrel pores in the membrane. The CDC/MACPF proteins contain a characteristic four-stranded β-sheet that is flanked by two α-helical bundles, which unfold to form two transmembrane β-hairpins. Apicomplexan eukaryotic parasites express CDC/MACPFs termed perforin-like proteins (PLPs). Here we review recent studies that provide key insights into the assembly and regulation of the Apicomplexan PLP (ApiMACPF) molecular pore-forming mechanisms, which are necessary for the osmotically driven rupture of the parasitophorous vacuole and host cell membrane, and cell traversal by these parasites.
Topics: Apicomplexa; Host-Pathogen Interactions; Macromolecular Substances; Perforin; Protein Conformation; Protein Multimerization
PubMed: 26025132
DOI: 10.1016/j.mib.2015.05.001 -
Biomedical Journal Feb 2017Apicomplexan parasites are responsible for a number of important human pathologies. Obviously, as Eukaryotes they share a number of cellular features and pathways with... (Review)
Review
Apicomplexan parasites are responsible for a number of important human pathologies. Obviously, as Eukaryotes they share a number of cellular features and pathways with their respective host cells. One of them is autophagy, a process involved in the degradation of the cell's own components. These intracellular parasites nonetheless seem to present a number of original features compared to their very evolutionarily distant host cells. In mammals and other metazoans, autophagy has been identified as an important contributor to the defence against microbial pathogens. Thus, host autophagy also likely plays a key role in the control of apicomplexan parasites, although its potential manipulation and subversion by intracellular parasites creates a complex interplay in the regulation of host and parasite autophagy. In this mini-review, we summarise current knowledge on autophagy in both parasites and their host cells, in the context of infection by three Apicomplexa: Plasmodium, Toxoplasma, and Theileria.
Topics: Animals; Autophagy; Host-Parasite Interactions; Humans; Parasites; Plasmodium; Theileria; Toxoplasma
PubMed: 28411879
DOI: 10.1016/j.bj.2017.01.001 -
Sub-cellular Biochemistry 2008Microneme secretion supports several key cellular processes including gliding motility, active cell invasion and migration through cells, biological barriers, and... (Review)
Review
Microneme secretion supports several key cellular processes including gliding motility, active cell invasion and migration through cells, biological barriers, and tissues. The modular design of microneme proteins enables these molecules to assist each other in folding and passage through the quality control system, accurately target to the micronemes, oligimerizing with other parasite proteins, and engaging a variety of host receptors for migration and cell invasion. Structural and biochemical analyses of MIC domains is providing new perspectives on how adhesion is regulated and the potentially distinct roles MICs might play in long or short range interactions during parasite attachment and entry. New access to complete genome sequences and ongoing advances in genetic manipulation should provide fertile ground for refining current models and defining exciting new roles for MICs in apicomplexan biology.
Topics: Animals; Apicomplexa; Cryptosporidium; Eimeria; Models, Biological; Protein Structure, Tertiary; Proteomics; Protozoan Proteins; Toxoplasma
PubMed: 18512339
DOI: 10.1007/978-0-387-78267-6_2 -
Trends in Parasitology Dec 2017Apicomplexan parasites Toxoplasma gondii and Plasmodium spp. use latent stages to persist in the host, facilitate transmission, and thwart treatment of infected... (Review)
Review
Apicomplexan parasites Toxoplasma gondii and Plasmodium spp. use latent stages to persist in the host, facilitate transmission, and thwart treatment of infected patients. Therefore, it is important to understand the processes driving parasite differentiation to and from quiescent stages. Here, we discuss how a family of protein kinases that phosphorylate the eukaryotic initiation factor-2 (eIF2) function in translational control and drive differentiation. This translational control culminates in reprogramming of the transcriptome to facilitate parasite transition towards latency. We also discuss how eIF2 phosphorylation contributes to the maintenance of latency and provides a crucial role in the timing of reactivation of latent parasites towards proliferative stages.
Topics: Apicomplexa; Eukaryotic Initiation Factor-2; Host-Parasite Interactions; Humans; Life Cycle Stages; Phosphorylation; Protozoan Proteins; Transcriptome
PubMed: 28942109
DOI: 10.1016/j.pt.2017.08.006 -
Nucleic Acids Research Jan 2009Full-Malaria/Parasites is a database for transcriptome studies of apicomplexa and other parasites, which is based on our original full-length cDNA sequences and physical...
Full-Malaria/Parasites is a database for transcriptome studies of apicomplexa and other parasites, which is based on our original full-length cDNA sequences and physical cDNA clone resources. In this update, the database has been expanded to contain the shogun sequencing for the entire sequences of 14,818 non-redundant full-length cDNA clones from six apicomplexa parasites and 6.8 million of transcription start sites (TSS), both of which had been produced by novel protocols using the oligo-capping method and the Illumina GA sequencer. The former should be the ultimate data for exact annotation of the expressed genes, while the latter should be useful for ultra-deep expression analysis. Furthermore, we have launched Full-Arthropods, a full-length cDNA database for arthropods of medical importance. Full-Arthropods contains 50 343 one-pass sequences, 10 399 shotgun complete sequences and 22.4 million TSS tags in anopheles mosquitoes that transmit malaria, tsetse flies that transmit trypanosomiasis and dust mites that cause allergic dermatitis and bronchial asthma. By providing the largest integrated full-length cDNA data resources in the apicomplexa parasites as well as their vectors, Full-Malaria/Parasites and Full-Arthropods should help combat parasitic diseases. Full-Malaria/Parasites and Full-Arthropods are accessible from http://fullmal.hgc.jp/.
Topics: Animals; Anopheles; Apicomplexa; Arthropod Vectors; Arthropods; DNA, Complementary; Databases, Nucleic Acid; Parasites; Plasmodium; Sequence Analysis, DNA; Toxoplasma; Transcription Initiation Site; Tsetse Flies
PubMed: 18987005
DOI: 10.1093/nar/gkn856 -
The Journal of Biological Chemistry Jan 2020The Apicomplexa phylum comprises diverse parasitic organisms that have evolved from a free-living ancestor. These obligate intracellular parasites exhibit versatile... (Review)
Review
The Apicomplexa phylum comprises diverse parasitic organisms that have evolved from a free-living ancestor. These obligate intracellular parasites exhibit versatile metabolic capabilities reflecting their capacity to survive and grow in different hosts and varying niches. Determined by nutrient availability, they either use their biosynthesis machineries or largely depend on their host for metabolite acquisition. Because vitamins cannot be synthesized by the mammalian host, the enzymes required for their synthesis in apicomplexan parasites represent a large repertoire of potential therapeutic targets. Here, we review recent advances in metabolic reconstruction and functional studies coupled to metabolomics that unravel the interplay between biosynthesis and salvage of vitamins and cofactors in apicomplexans. A particular emphasis is placed on , during both its acute and latent stages of infection.
Topics: Apicomplexa; Coenzymes; Host-Parasite Interactions; Humans; Metabolic Networks and Pathways; Protein Biosynthesis; Toxoplasma; Toxoplasmosis; Vitamins
PubMed: 31767680
DOI: 10.1074/jbc.AW119.008150 -
The International Journal of... Oct 2009Without mitochondria, eukaryotic cells would depend entirely on anaerobic glycolysis for ATP generation. This also holds true for protists, both free-living and... (Review)
Review
Without mitochondria, eukaryotic cells would depend entirely on anaerobic glycolysis for ATP generation. This also holds true for protists, both free-living and parasitic. Parasitic protists include agents of human and animal diseases that have a huge impact on world populations. In the phylum Apicomplexa, several species of Plasmodium cause malaria, whereas Toxoplasma gondii is a cosmopolite parasite found on all continents. Flagellates of the order Kinetoplastida include the genera Leishmania and Trypanosoma causative agents of human leishmaniasis and (depending on the species) African trypanosomiasis and Chagas disease. Although clearly distinct in many aspects, the members of these two groups bear a single and usually well developed mitochondrion. The single mitochondrion of Apicomplexa has a dense matrix and many cristae with a circular profile. The organelle is even more peculiar in the order Kinetoplastida, exhibiting a condensed network of DNA at a specific position, always close to the flagellar basal body. This arrangement is known as Kinetoplast and the name of the order derived from it. Kinetoplastids also bear glycosomes, peroxisomes that concentrate enzymes of the glycolytic cycle. Mitochondrial volume and activity is maximum when glycosomal is low and vice versa. In both Apicomplexa and trypanosomatids, mitochondria show particularities that are absent in other eukaryotic organisms. These peculiar features make them an attractive target for therapeutic drugs for the diseases they cause.
Topics: Animals; Antiparasitic Agents; Apicomplexa; Electron Transport; Humans; Kinetoplastida; Lipid Metabolism; Mitochondria
PubMed: 19379828
DOI: 10.1016/j.biocel.2009.04.007