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Trends in Parasitology Aug 2020The phylum Apicomplexa has been defined by the presence of the apical complex, a structure composed of secretory organelles and specific cytoskeletal elements. A... (Review)
Review
The phylum Apicomplexa has been defined by the presence of the apical complex, a structure composed of secretory organelles and specific cytoskeletal elements. A conspicuous feature of the apical complex in many apicomplexans is the conoid, a hollow tapered barrel structure composed of tubulin fibers. In Toxoplasma gondii, the apical complex is a central site of convergence for calcium-related and lipid-mediated signaling pathways that coordinate conoid protrusion, microneme secretion, and actin polymerization, to initiate gliding motility. Through cutting-edge technologies, great progress has recently been made in discovering the structural subcomponents and proteins implicated in the biogenesis and stability of the apical complex and, in turn, these discoveries have shed new light on the function and evolution of this definitive structure.
Topics: Apicomplexa; Biological Evolution; Organelles; Protozoan Proteins; Toxoplasma
PubMed: 32487504
DOI: 10.1016/j.pt.2020.05.001 -
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 -
Trends in Parasitology Sep 2018Increased parasite burden is linked to the severity of clinical disease caused by Apicomplexa parasites such as Toxoplasma gondii, Plasmodium spp, and Cryptosporidium.... (Review)
Review
Increased parasite burden is linked to the severity of clinical disease caused by Apicomplexa parasites such as Toxoplasma gondii, Plasmodium spp, and Cryptosporidium. Pathogenesis of apicomplexan infections is greatly affected by the growth rate of the parasite asexual stages. This review discusses recent advances in deciphering the mitotic structures and cell cycle regulatory factors required by Apicomplexa parasites to replicate. As the molecular details become clearer, it is evident that the highly unconventional cell cycles of these parasites is a blending of many ancient and borrowed elements, which were then adapted to enable apicomplexan proliferation in a wide variety of different animal hosts.
Topics: Apicomplexa; Cell Cycle; Host-Parasite Interactions; Protozoan Infections
PubMed: 30078701
DOI: 10.1016/j.pt.2018.07.006 -
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 -
Trends in Parasitology Dec 2019Phosphoinositides (or phosphatidylinositol phosphates, PIPs) are low-abundance membrane phospholipids that act, in conjunction with their binding partners, as important... (Review)
Review
Phosphoinositides (or phosphatidylinositol phosphates, PIPs) are low-abundance membrane phospholipids that act, in conjunction with their binding partners, as important constitutive signals defining biochemical organelle identity as well as membrane trafficking and signal transduction at eukaryotic cellular membranes. In this review, we present roles for PIP residues and PIP-binding proteins in endocytosis and autophagy in protist parasites such as Trypanosoma brucei, Toxoplasma gondii, Plasmodium falciparum, Entamoeba histolytica, and Giardia lamblia. Molecular parasitologists with an interest in comparative cell and molecular biology of membrane trafficking in protist lineages beyond the phylum Apicomplexa, along with cell and molecular biologists generally interested in the diversification of membrane trafficking in eukaryotes, will hopefully find this review to be a useful resource.
Topics: Apicomplexa; Autophagy; Carrier Proteins; Endocytosis; Phosphatidylinositols; Protein Transport; Signal Transduction
PubMed: 31615721
DOI: 10.1016/j.pt.2019.08.008 -
Molecular Microbiology Apr 2024Apicomplexan parasites are aetiological agents of numerous diseases in humans and livestock. Functional genomics studies in these parasites enable the identification of... (Review)
Review
Apicomplexan parasites are aetiological agents of numerous diseases in humans and livestock. Functional genomics studies in these parasites enable the identification of biological mechanisms and protein functions that can be targeted for therapeutic intervention. Recent improvements in forward genetics and whole-genome screens utilising CRISPR/Cas technology have revolutionised the functional analysis of genes during Apicomplexan infection of host cells. Here, we highlight key discoveries from CRISPR/Cas9 screens in Apicomplexa or their infected host cells and discuss remaining challenges to maximise this technology that may help answer fundamental questions about parasite-host interactions.
Topics: Humans; Animals; CRISPR-Cas Systems; Genome; Apicomplexa; Parasites; Host-Parasite Interactions
PubMed: 38225194
DOI: 10.1111/mmi.15221 -
Parasitology Apr 2018Cryptosporidium spp. (Apicomplexa) causing cryptosporidiosis are of medical and veterinary significance. The genus Cryptosporidium has benefited from the application of... (Review)
Review
Cryptosporidium spp. (Apicomplexa) causing cryptosporidiosis are of medical and veterinary significance. The genus Cryptosporidium has benefited from the application of what is considered a DNA-barcoding approach, even before the term 'DNA barcoding' was formally coined. Here, the objective to define the DNA barcode diversity of Cryptosporidium infecting mammals is reviewed and considered to be accomplished. Within the Cryptosporidium literature, the distinction between DNA barcoding and DNA taxonomy is indistinct. DNA barcoding and DNA taxonomy are examined using the latest additions to the growing spectrum of named Cryptosporidium species and within-species and between-species identity is revisited. Ease and availability of whole-genome DNA sequencing of the relatively small Cryptosporidium genome offer an initial perspective on the intra-host diversity. The opportunity emerges to apply a metagenomic approach to purified field/clinical Cryptosporidum isolates. The outstanding question remains a reliable definition of Cryptosporidium phenotype. The complementary experimental infections and metagenome approach will need to be applied simultaneously to address Cryptosporidium phenotype with carefully chosen clinical evaluations enabling identification of virulence factors.
Topics: Cryptosporidium; DNA Barcoding, Taxonomic; Genetic Variation; Metagenome; Phenotype; Virulence Factors; Whole Genome Sequencing
PubMed: 29113613
DOI: 10.1017/S0031182017001809 -
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 -
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 -
Molecular Microbiology May 2021Babesia species are tick-borne intracellular parasites that infect the red blood cells of their mammalian host, leading to severe or fatal disease. Babesia spp. infect a... (Review)
Review
Babesia species are tick-borne intracellular parasites that infect the red blood cells of their mammalian host, leading to severe or fatal disease. Babesia spp. infect a wide range of mammalian species and cause a significant economic burden globally, predominantly through disease in cattle. Several Babesia spp. are increasingly being recognized as zoonotic pathogens of humans. Babesia spp. have complex life cycles involving multiple stages in the tick and the mammalian host. The parasite utilizes complex signaling pathways during replication, egress, and invasion in each of these stages. They must also rapidly respond to their environment when switching between the mammalian and tick stages. This review will focus on the signaling pathways and environmental stimuli that Babesia spp. utilize in the bloodstream and for transmission to the tick, with an emphasis on the role of phosphorylation- and calcium-based signaling during egress and invasion. The expanding availability of in vitro and in vivo culture systems, genomes, transcriptomes, and transgenic systems available for a range of Babesia spp. should encourage further biological and translational studies of these ubiquitous parasites.
Topics: Animals; Babesia; Babesiosis; Humans; Life Cycle Stages; Protozoan Proteins; Signal Transduction; Ticks
PubMed: 33274587
DOI: 10.1111/mmi.14650