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Frontiers in Cellular and Infection... 2021
Topics: Animals; Apicomplexa; Gastrointestinal Tract; Host-Parasite Interactions; Invertebrates; Parasites; Vertebrates
PubMed: 33996642
DOI: 10.3389/fcimb.2021.680555 -
Essays in Biochemistry 2011Calcium is relevant for several vital functions in apicomplexan parasites, including host cell invasion, parasite motility and differentiation. The ER (endoplasmic... (Review)
Review
Calcium is relevant for several vital functions in apicomplexan parasites, including host cell invasion, parasite motility and differentiation. The ER (endoplasmic reticulum) and calcium-rich acidocalcisomes have been identified as major calcium stores. Other potential calcium-storage organelles include the Golgi, the mitochondrion, the apicoplast and the recently described plant-like vacuole in Toxoplasma gondii. Compared with most eukaryotic systems, apicomplexan parasites contain a reduced number of calcium-related genes, a vast majority of which remain uncharacterized. Several Ca²⁺-ATPases have been described in apicomplexans, several of which are annotated in the different genomes. There is experimental evidence for an IP3 (inositol 1,4,5-trisphosphate)-dependent calcium response in Plasmodium spp. and T. gondii, although no IP3 or ryanodine receptors have been identified. Genes encoding potential calcium channels are present in T. gondi, but not in Plasmodium spp. and Cryptosporidium spp. Effector calcium-binding proteins including calmodulins and CDPK (calcium-dependent protein kinase) genes mainly found in plants have also been described. The characterized CDPKs were found to play important roles in protein secretion, host cell invasion and parasite differentiation. Taken together, the available information on calcium storage and function in apicomplexans, although fragmented, suggest the existence of unique calcium-mediated pathways in these parasites. An in-depth functional characterization of the apicomplexan calcium-related genes could lead to the identification of novel therapeutic targets, and will improve our understanding of the role of calcium in parasite development and virulence.
Topics: Animals; Apicomplexa; Calcium; Calcium Channels; Calcium-Binding Proteins; Calcium-Transporting ATPases; Endoplasmic Reticulum; Inositol 1,4,5-Trisphosphate; Mitochondria; Protein Kinases; Protozoan Infections
PubMed: 22023444
DOI: 10.1042/bse0510097 -
Nucleic Acids Research Jan 2022The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As...
The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC.
Topics: Animals; Apicomplexa; Bacteria; Communicable Diseases; Computational Biology; Data Mining; Databases, Factual; Diplomonadida; Disease Vectors; Fungi; Host-Pathogen Interactions; Humans; Insecta; Internet; Nematoda; Phenotype; Phylogeny; User-Computer Interface; Virulence; Workflow
PubMed: 34718728
DOI: 10.1093/nar/gkab929 -
Parasitology Research Jul 2010Apicomplexa are primarily obligate intracellular protozoa that have evolved complex developmental stages important for pathogenesis and transmission. Toxoplasma gondii,... (Review)
Review
Apicomplexa are primarily obligate intracellular protozoa that have evolved complex developmental stages important for pathogenesis and transmission. Toxoplasma gondii, responsible for the disease toxoplasmosis, has the broadest host range of the Apicomplexa as it infects virtually any warm-blooded vertebrate host. Key to T. gondii's pathogenesis is its ability to differentiate from a rapidly replicating tachyzoite stage during acute infection to a relatively non-immunogenic, dormant bradyzoite stage contained in tissue cysts. These bradyzoite cysts can reconvert back to tachyzoites years later causing serious pathology and death if a person becomes immune-compromised. Like the sexual stage sporozoites, bradyzoites are also orally infectious and a major contributor to transmission. Because of the critical role of stage conversion to pathogenesis and transmission, a major research focus is aimed at identifying molecular mediators and pathways that regulate differentiation. Tachyzoite to bradyzoite development can occur spontaneously in vitro and be induced in response to exogenous stress including but not limited to host immunity. The purpose of this review is to explore the potential contributors to stage differentiation in infection and how a determination is made by the parasite to differentiate from tachyzoites to bradyzoites.
Topics: Animals; Gene Expression Regulation; Humans; Toxoplasma
PubMed: 20514494
DOI: 10.1007/s00436-010-1899-6 -
Frontiers in Cellular and Infection... 2020Apicomplexan parasites, such as human malaria parasites, have complex lifecycles encompassing multiple and diverse environmental niches. Invading, replicating, and... (Review)
Review
Apicomplexan parasites, such as human malaria parasites, have complex lifecycles encompassing multiple and diverse environmental niches. Invading, replicating, and escaping from different cell types, along with exploiting each intracellular niche, necessitate large and dynamic changes in parasite morphology and cellular architecture. The inner membrane complex (IMC) is a unique structural element that is intricately involved with these distinct morphological changes. The IMC is a double membrane organelle that forms and is located beneath the plasma membrane of these single-celled organisms. In spp. parasites it has three major purposes: it confers stability and shape to the cell, functions as an important scaffolding compartment during the formation of daughter cells, and plays a major role in motility and invasion. Recent years have revealed greater insights into the architecture, protein composition and function of the IMC. Here, we discuss the multiple roles of the IMC in each parasite lifecycle stage as well as insights into its sub-compartmentalization, biogenesis, disassembly and regulation during stage conversion of .
Topics: Animals; Cell Membrane; Humans; Malaria; Parasites; Plasmodium; Plasmodium falciparum; Protozoan Proteins
PubMed: 33489940
DOI: 10.3389/fcimb.2020.611801 -
Molecular and Biochemical Parasitology Sep 2024Apicomplexan parasites are the primary causative agents of many human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. These opportunistic pathogens... (Review)
Review
Apicomplexan parasites are the primary causative agents of many human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. These opportunistic pathogens undergo complex life cycles with multiple developmental stages, wherein many key steps are regulated by phosphorylation mechanisms. The genomes of apicomplexan pathogens contain protein kinases from different groups including tyrosine kinase-like (TKL) family proteins. Although information on the role of TKL kinases in apicomplexans is quite limited, recent studies have revealed the important role of this family of proteins in apicomplexan biology. TKL kinases in these protozoan pathogens show unique organization with many novel domains thus making them attractive candidates for drug development. In this mini review, we summarize the current understanding of the role of TKL kinases in human apicomplexan pathogens' (Toxoplasma gondii, Plasmodium falciparum and Cryptosporidium parvum) biology and pathogenesis.
Topics: Humans; Toxoplasma; Cryptosporidium parvum; Protozoan Proteins; Plasmodium falciparum; Apicomplexa; Protein-Tyrosine Kinases; Phosphorylation
PubMed: 38719028
DOI: 10.1016/j.molbiopara.2024.111628 -
Protist Dec 2010Plastids are found across the tree of life in a tremendous diversity of life forms. Surprisingly they are not limited to photosynthetic organisms but also found in... (Review)
Review
Plastids are found across the tree of life in a tremendous diversity of life forms. Surprisingly they are not limited to photosynthetic organisms but also found in numerous predators and parasites. An important reason for the pervasiveness of plastids has been their ability to move laterally and to jump from one branch of the tree of life to the next through secondary endosymbiosis. Eukaryotic algae have entered endosymbiotic relationships with other eukaryotes on multiple independent occasions. The descendants of these endosymbiotic events now carry complex plastids, organelles that are bound by three or even four membranes. As in all endosymbiotic organelles most of the symbiont's genes have been transferred to the host and their protein products have to be imported into the organelle. As four membranes might suggest, this is a complex process. The emerging mechanisms display a series of translocons that mirror the divergent ancestry of the membranes they cross. This review is written from the viewpoint of a parasite biologist and seeks to provide a brief overview of plastid evolution in particular for readers not already familiar with plant and algal biology and then focuses on recent molecular discoveries using genetically tractable Apicomplexa and diatoms.
Topics: Apicomplexa; Biological Evolution; Diatoms; Eukaryota; Plastids; Protein Transport; Proteins
PubMed: 21036664
DOI: 10.1016/j.protis.2010.09.002 -
Parasitology Aug 2018Although the application of CRISPR/Cas9 genome engineering approaches was first reported in apicomplexan parasites only 3 years ago, this technology has rapidly become... (Review)
Review
Although the application of CRISPR/Cas9 genome engineering approaches was first reported in apicomplexan parasites only 3 years ago, this technology has rapidly become an essential component of research on apicomplexan parasites. This review briefly describes the history of CRISPR/Cas9 and the principles behind its use along with documenting its implementation in apicomplexan parasites, especially Plasmodium spp. and Toxoplasma gondii. We also discuss the recent use of CRISPR/Cas9 for whole genome screening of gene knockout mutants in T. gondii and highlight its use for seminal genetic manipulations of Cryptosporidium spp. Finally, we consider new variations of CRISPR/Cas9 that have yet to be implemented in apicomplexans. Whereas CRISPR/Cas9 has already accelerated rapid interrogation of gene function in apicomplexans, the full potential of this technology is yet to be realized as new variations and innovations are integrated into the field.
Topics: Animals; Apicomplexa; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Cryptosporidium; Gene Knockout Techniques; Genetic Engineering; Genome, Protozoan; Humans; Mice; Plasmodium; Recombination, Genetic; Toxoplasma
PubMed: 29463318
DOI: 10.1017/S003118201800001X -
International Journal For Parasitology May 2020Toxoplasma gondii is remarkably unique in its ability to successfully infect vertebrate hosts from multiple phyla and can successfully infect most cells within these... (Review)
Review
Toxoplasma gondii is remarkably unique in its ability to successfully infect vertebrate hosts from multiple phyla and can successfully infect most cells within these organisms. The infection outcome in each of these species is determined by the complex interaction between parasite and host genotype. As techniques to quantify global changes in cell function become more readily available and precise, new data are coming to light about how (i) different host cell types respond to parasitic infection and (ii) different parasite species impact the host. Here we focus on recent studies comparing the response to intracellular parasitism by different cell types and insights into understanding host-parasite interactions from comparative studies on T. gondii and its close extant relatives.
Topics: Animals; Apicomplexa; Biological Evolution; Cell Line; Chemokines; Coccidiosis; Gene Expression; Host Specificity; Host-Parasite Interactions; Humans; Immunity; Interferon-gamma; Mammals; Neospora; Protein Serine-Threonine Kinases; Protozoan Proteins; THP-1 Cells; Toxoplasma; Toxoplasmosis; Transcriptome; Tumor Suppressor Protein p53; Virulence
PubMed: 32407716
DOI: 10.1016/j.ijpara.2020.05.001 -
Traffic (Copenhagen, Denmark) May 2008The invasive stages of Apicomplexa parasites, called zoites, have been largely studied in in vitro systems, with a special emphasis on their unique gliding and host cell... (Review)
Review
The invasive stages of Apicomplexa parasites, called zoites, have been largely studied in in vitro systems, with a special emphasis on their unique gliding and host cell invasive capacities. In contrast, the means by which these parasites reach their destination in their hosts are still poorly understood. We summarize here our current understanding of the cellular basis of in vivo parasitism by two well-studied Apicomplexa zoites, the Toxoplasma tachyzoite and the Plasmodium sporozoite. Despite being close relatives, these two zoites use different strategies to reach their goal and establish infection.
Topics: Animals; Apicomplexa; Blood Vessels; Cell Movement; Host-Parasite Interactions; Humans; Liver; Malaria; Plasmodium; Protozoan Proteins; Sporozoites; Toxoplasma; Toxoplasmosis
PubMed: 18194412
DOI: 10.1111/j.1600-0854.2008.00703.x