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Trends in Parasitology Dec 2020Parasitic protozoa of the phylum Apicomplexa cause a range of human and animal diseases. Their complex life cycles - often heteroxenous with sexual and asexual phases in... (Review)
Review
Parasitic protozoa of the phylum Apicomplexa cause a range of human and animal diseases. Their complex life cycles - often heteroxenous with sexual and asexual phases in different hosts - rely on elaborate cytoskeletal structures to enable morphogenesis and motility, organize cell division, and withstand diverse environmental forces. This review primarily focuses on studies using Toxoplasma gondii and Plasmodium spp. as the best studied apicomplexans; however, many cytoskeletal adaptations are broadly conserved and predate the emergence of the parasitic phylum. After decades cataloguing the constituents of such structures, a dynamic picture is emerging of the assembly and maintenance of apicomplexan cytoskeletons, illuminating how they template and orient critical processes during infection. These observations impact our view of eukaryotic diversity and offer future challenges for cell biology.
Topics: Adaptation, Physiological; Animals; Apicomplexa; Cytoskeleton; Humans; Life Cycle Stages; Plasmodium; Toxoplasma
PubMed: 33011071
DOI: 10.1016/j.pt.2020.09.001 -
Current Topics in Medicinal Chemistry 2017Phosphoinositides (PIs) and their derivatives are essential cellular components that form the building blocks for cell membranes and regulate numerous cell functions.... (Review)
Review
BACKGROUND
Phosphoinositides (PIs) and their derivatives are essential cellular components that form the building blocks for cell membranes and regulate numerous cell functions. Specifically, the ability to generate myo-inositol 1,4,5-trisphosphate (InsP3) via phospholipase C (PLC) dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to InsP3 and diacylglycerol (DAG) initiates intracellular calcium signaling events representing a fundamental signaling mechanism dependent on PIs. InsP3 produced by PI turnover as a second messenger causes intracellular calcium release, especially from endoplasmic reticulum, by binding to the InsP3 receptor (InsP3R). Various PIs and the enzymes, such as phosphatidylinositol synthase and phosphatidylinositol 4-kinase, necessary for their turnover have been characterized in Apicomplexa, a large phylum of mostly commensal organisms that also includes several clinically relevant parasites. However, InsP3Rs have not been identified in genomes of apicomplexans, despite evidence that these parasites produce InsP3 that mediates intracellular Ca2+ signaling.
CONCLUSION
Evidence to supporting IP3-dependent signaling cascades in apicomplexans suggests that they may harbor a primitive or non-canonical InsP3R. Understanding these pathways may be informative about early branching eukaryotes, where such signaling pathways also diverge from animal systems, thus identifying potential novel and essential targets for therapeutic intervention.
Topics: Animals; Apicomplexa; Inositol 1,4,5-Trisphosphate; Second Messenger Systems; Signal Transduction
PubMed: 28137231
DOI: 10.2174/1568026617666170130121042 -
Cellular Microbiology Aug 2015The epigenetics of host-pathogen interactions is emerging as an interesting angle from which to study how parasites have evolved sophisticated strategies to manipulate... (Review)
Review
The epigenetics of host-pathogen interactions is emerging as an interesting angle from which to study how parasites have evolved sophisticated strategies to manipulate host gene transcription and protein expression. In this review, we discuss the application of an operational framework to investigate the host cell signalling pathways that are induced by intracellular parasites and the epigenomic consequences in the host nucleus. To illustrate this conceptual approach, we have focused on examples from two eukaryotic intracellular parasites of the apicomplexa phylum: Theileria and Toxoplasma. We review recent findings on intracellular parasitism strategies for hijacking host nuclear functions and discuss how we might think of the parasite and its proteome as an intracellular epigenator.
Topics: Cytoplasm; Epigenesis, Genetic; Gene Expression Regulation; Host-Parasite Interactions; Immune Evasion; Theileria; Toxoplasma
PubMed: 26096716
DOI: 10.1111/cmi.12471 -
Molecular Microbiology Oct 2017The balance between phosphorylation and de-phosphorylation, which is delicately regulated by protein kinases and phosphatases, is critical for nearly all biological... (Review)
Review
The balance between phosphorylation and de-phosphorylation, which is delicately regulated by protein kinases and phosphatases, is critical for nearly all biological processes. The Apicomplexa are a large phylum which contains various parasitic protists, including human pathogens, such as Plasmodium, Toxoplasma, Cryptosporidium and Babesia species. The diverse life cycles of these parasites are highly complex and, not surprisingly, many of their key steps are exquisitely regulated by phosphorylation. Interestingly, many of the kinases and phosphatases, as well as the substrates involved in these events are unique to the parasites and therefore phosphorylation constitutes a viable target for antiparasitic intervention. Most progress on this realm has come from studies in Toxoplasma and Plasmodium of their respective kinomes and phosphoproteomes. Nonetheless, given their likely importance, phosphatases have recently become the focus of research within the apicomplexan parasites. In this review, we concentrate on serine/threonine phosphatases in apicomplexan parasites, with the focus on comprehensively identifying and naming protein phosphatases in available apicomplexan genomes, and summarizing the progress of their functional analyses in recent years.
Topics: Animals; Apicomplexa; Conserved Sequence; Genome; Humans; Parasites; Phosphoprotein Phosphatases; Phosphorylation; Phosphotransferases; Phylogeny; Plasmodium; Toxoplasma
PubMed: 28556455
DOI: 10.1111/mmi.13715 -
Nature Reviews. Microbiology Nov 2017Protozoan parasites have developed elaborate motility systems that facilitate infection and dissemination. For example, amoebae use actin-rich membrane extensions called... (Review)
Review
Protozoan parasites have developed elaborate motility systems that facilitate infection and dissemination. For example, amoebae use actin-rich membrane extensions called pseudopodia, whereas Kinetoplastida are propelled by microtubule-containing flagella. By contrast, the motile and invasive stages of the Apicomplexa - a phylum that contains the important human pathogens Plasmodium falciparum (which causes malaria) and Toxoplasma gondii (which causes toxoplasmosis) - have a unique machinery called the glideosome, which is composed of an actomyosin system that underlies the plasma membrane. The glideosome promotes substrate-dependent gliding motility, which powers migration across biological barriers, as well as active host cell entry and egress from infected cells. In this Review, we discuss the discovery of the principles that govern gliding motility, the characterization of the molecular machinery involved, and its impact on parasite invasion and egress from infected cells.
Topics: Actin Cytoskeleton; Actins; Animals; Apicomplexa; Cell Membrane; Cell Movement; Host-Parasite Interactions; Humans; Models, Biological; Plasmodium falciparum; Protozoan Proteins; Toxoplasma
PubMed: 28867819
DOI: 10.1038/nrmicro.2017.86 -
International Journal For Parasitology Jun 2018Phosphoinositides are the phosphorylated derivatives of the structural membrane phospholipid phosphatidylinositol. Single or combined phosphorylation at the 3, 4 and 5... (Review)
Review
Phosphoinositides are the phosphorylated derivatives of the structural membrane phospholipid phosphatidylinositol. Single or combined phosphorylation at the 3, 4 and 5 positions of the inositol ring gives rise to the seven different species of phosphoinositides. All are quantitatively minor components of cellular membranes but have been shown to have important functions in multiple cellular processes. Here we describe our current knowledge of phosphoinositide metabolism and functions in apicomplexan parasites, mainly focusing on Toxoplasma gondii and Plasmodium spp. Even though our understanding is still rudimentary, phosphoinositides have already shown their importance in parasite biology and revealed some very particular and parasite-specific functions. Not surprisingly, there is a strong potential for phosphoinositide synthesis to be exploited for future anti-parasitic drug development.
Topics: Animals; Apicomplexa; Lipid Metabolism; Parasites; Phosphatidylinositols
PubMed: 29596862
DOI: 10.1016/j.ijpara.2018.01.009 -
Chembiochem : a European Journal of... Sep 2023Natural product discovery has traditionally relied on the isolation of small molecules from producing species, but genome-sequencing technology and advances in molecular... (Review)
Review
Natural product discovery has traditionally relied on the isolation of small molecules from producing species, but genome-sequencing technology and advances in molecular biology techniques have expanded efforts to a wider array of organisms. Protists represent an underexplored kingdom for specialized metabolite searches despite bioinformatic analysis that suggests they harbor distinct biologically active small molecules. Specifically, pathogenic apicomplexan parasites, responsible for billions of global infections, have been found to possess multiple biosynthetic gene clusters, which hints at their capacity to produce polyketide metabolites. Biochemical studies have revealed unique features of apicomplexan polyketide synthases, but to date, the identity and function of the polyketides synthesized by these megaenzymes remains unknown. Herein, we discuss the potential for specialized metabolite production in protists and the possible evolution of polyketide biosynthetic gene clusters in apicomplexan parasites. We then focus on a polyketide synthase from the apicomplexan Toxoplasma gondii to discuss the unique domain architecture and properties of these proteins when compared to previously characterized systems, and further speculate on the possible functions for polyketides in these pathogenic parasites.
Topics: Secondary Metabolism; Polyketide Synthases; Computational Biology; Apicomplexa; Polyketides
PubMed: 37171468
DOI: 10.1002/cbic.202300263 -
Seminars in Cell & Developmental Biology Oct 2015Apicomplexan parasites, including Plasmodium and Toxoplasma, employ a unique form of substrate-dependent locomotion known as gliding motility. In these obligate,... (Review)
Review
Apicomplexan parasites, including Plasmodium and Toxoplasma, employ a unique form of substrate-dependent locomotion known as gliding motility. In these obligate, intracellular parasites, gliding motility is used for migration through the tissues and cells of the host, for active penetration of the host cell, and, at times, for proactive egress from the host. Gliding motility is powered by an actin-myosin based motor apparatus, known as the glideosome, which is situated within the elaborate cortical domain of the parasite. In this system, myosin is anchored to an internal membrane complex and drives the rearward translocation of actin-associated cell surface adhesins, thus leading to forward movement of the parasite. This review outlines our current understanding of glideosome architecture and the molecular basis of parasite motility.
Topics: Actins; Animals; Apicomplexa; Host-Parasite Interactions; Humans; Locomotion; Microscopy, Electron; Models, Biological; Myosins; Parasitic Diseases
PubMed: 26428297
DOI: 10.1016/j.semcdb.2015.09.020 -
Frontiers in Cellular and Infection... 2017The next-generation gene editing based on CRISPR (clustered regularly interspaced short palindromic repeats) has been successfully implemented in a wide range of... (Review)
Review
The next-generation gene editing based on CRISPR (clustered regularly interspaced short palindromic repeats) has been successfully implemented in a wide range of organisms including some protozoan parasites. However, application of such a versatile game-changing technology in molecular parasitology remains fairly underexplored. Here, we briefly introduce in human and mouse research and usher new directions to drive the parasitology research in the years to come. In precise, we outline contemporary ways to embolden existing apicomplexan and kinetoplastid parasite models by commissioning front-line gene-tailoring methods, and illustrate how we can break the enduring gridlock of gene manipulation in non-model parasitic protists to tackle intriguing questions that remain long unresolved otherwise. We show how a judicious solicitation of the CRISPR technology can eventually balance out the two facets of pathogen-host interplay.
Topics: Animals; Apicomplexa; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; Humans; Kinetoplastida; Phylogeny; Protozoan Infections
PubMed: 28730142
DOI: 10.3389/fcimb.2017.00292 -
BMC Genomics May 2022Genome architecture describes how genes and other features are arranged in genomes. These arrangements reflect the evolutionary pressures on genomes and underlie...
Genome architecture describes how genes and other features are arranged in genomes. These arrangements reflect the evolutionary pressures on genomes and underlie biological processes such as chromosomal segregation and the regulation of gene expression. We present a new tool called Genome Decomposition Analysis (GDA) that characterises genome architectures and acts as an accessible approach for discovering hidden features of a genome assembly. With the imminent deluge of high-quality genome assemblies from projects such as the Darwin Tree of Life and the Earth BioGenome Project, GDA has been designed to facilitate their exploration and the discovery of novel genome biology. We highlight the effectiveness of our approach in characterising the genome architectures of single-celled eukaryotic parasites from the phylum Apicomplexa and show that it scales well to large genomes.
Topics: Animals; Apicomplexa; Biological Evolution; Eukaryota; Genome; Parasites
PubMed: 35610562
DOI: 10.1186/s12864-022-08616-3