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Microbiology and Molecular Biology... Jun 2022Parasites belonging to the Apicomplexa phylum are among the most successful pathogens known in nature. They can infect a wide range of hosts, often remain undetected by... (Review)
Review
Parasites belonging to the Apicomplexa phylum are among the most successful pathogens known in nature. They can infect a wide range of hosts, often remain undetected by the immune system, and cause acute and chronic illness. In this phylum, we can find parasites of human and veterinary health relevance, such as , , , and . There are still many unknowns about the biology of these pathogens due to the ethical and practical issues of performing research in their natural hosts. Animal models are often difficult or nonexistent, and as a result, there are apicomplexan life cycle stages that have not been studied. One recent alternative has been the use of three-dimensional (3D) systems such as organoids, 3D scaffolds with different matrices, microfluidic devices, organs-on-a-chip, and other tissue culture models. These 3D systems have facilitated and expanded the research of apicomplexans, allowing us to explore life stages that were previously out of reach and experimental procedures that were practically impossible to perform in animal models. Human- and animal-derived 3D systems can be obtained from different organs, allowing us to model host-pathogen interactions for diagnostic methods and vaccine development, drug testing, exploratory biology, and other applications. In this review, we summarize the most recent advances in the use of 3D systems applied to apicomplexans. We show the wide array of strategies that have been successfully used so far and apply them to explore other organisms that have been less studied.
Topics: Animals; Apicomplexa; Cryptosporidiosis; Cryptosporidium; Parasites; Plasmodium; Toxoplasma
PubMed: 35412359
DOI: 10.1128/mmbr.00025-22 -
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 -
Biomolecules Aug 2019The phylum Apicomplexa (Alveolates) comprises a group of host-associated protists, predominately intracellular parasites, including devastating parasites like , the... (Review)
Review
The phylum Apicomplexa (Alveolates) comprises a group of host-associated protists, predominately intracellular parasites, including devastating parasites like , the causative agent of malaria. One of the more fascinating characteristics of Apicomplexa is their highly reduced (and occasionally lost) remnant plastid, termed the apicoplast. Four core metabolic pathways are retained in the apicoplast: heme synthesis, iron-sulfur cluster synthesis, isoprenoid synthesis, and fatty acid synthesis. It has been suggested that one or more of these pathways are essential for plastid and plastid genome retention. The past decade has witnessed the discovery of several apicomplexan relatives, and next-generation sequencing efforts are revealing that they retain variable plastid metabolic capacities. These data are providing clues about the core genes and pathways of reduced plastids, while at the same time further confounding our view on the evolutionary history of the apicoplast. Here, we examine the evolutionary history of the apicoplast, explore plastid metabolism in Apicomplexa and their close relatives, and propose that the differences among reduced plastids result from a game of endosymbiotic roulette. Continued exploration of the Apicomplexa and their relatives is sure to provide new insights into the evolution of the apicoplast and apicomplexans as a whole.
Topics: Apicomplexa; Light
PubMed: 31430853
DOI: 10.3390/biom9080378 -
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 -
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 Mar 2004Toxoplasma gondii is an obligate intracellular protozoan parasite which is a significant human and veterinary pathogen. Other members of the phylum Apicomplexa are also... (Review)
Review
Toxoplasma gondii is an obligate intracellular protozoan parasite which is a significant human and veterinary pathogen. Other members of the phylum Apicomplexa are also important pathogens including Plasmodium species (i.e. malaria), Eimeria species, Neospora, Babesia, Theileria and Cryptosporidium. Unlike most of these organisms, T. gondii is readily amenable to genetic manipulation in the laboratory. Cell biology studies are more readily performed in T. gondii due to the high efficiency of transient and stable transfection, the availability of many cell markers, and the relative ease with which the parasite can be studied using advanced microscopic techniques. Thus, for many experimental questions, T. gondii remains the best model system to study the biology of the Apicomplexa. Our understanding of the mechanisms of drug resistance, the biology of the apicoplast, and the process of host cell invasion has been advanced by studies in T. gondii. Heterologous expression of apicomplexan proteins in T. gondii has frequently facilitated further characterisation of proteins that could not be easily studied. Recent studies of Apicomplexa have been complemented by genome sequencing projects that have facilitated discovery of surprising differences in cell biology and metabolism between Apicomplexa. While results in T. gondii will not always be applicable to other Apicomplexa, T. gondii remains an important model system for understanding the biology of apicomplexan parasites.
Topics: Animals; Antiprotozoal Agents; Genes, Protozoan; Models, Biological; Purines; Pyrimidines; Toxoplasma
PubMed: 15003501
DOI: 10.1016/j.ijpara.2003.12.009 -
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 -
Cell Host & Microbe Jun 2009The phylum Apicomplexa includes a large and diverse group of obligate intracellular parasites that rely on actomyosin-based motility to migrate, enter host cells, and... (Review)
Review
The phylum Apicomplexa includes a large and diverse group of obligate intracellular parasites that rely on actomyosin-based motility to migrate, enter host cells, and egress from infected cells. To ensure their intracellular survival and replication, the apicomplexans have evolved sophisticated strategies for subversion of the host cytoskeleton. Given the properties in common between the host and parasite cytoskeleton, dissecting their individual contribution to the establishment of parasitic infection has been challenging. Nevertheless, recent studies have provided new insights into the mechanisms by which parasites subvert the dynamic properties of host actin and tubulin to promote their entry, development, and egress.
Topics: Actins; Animals; Apicomplexa; Cytoskeleton; Host-Parasite Interactions; Models, Biological; Tubulin
PubMed: 19527887
DOI: 10.1016/j.chom.2009.05.013 -
Anais Da Academia Brasileira de Ciencias Jun 2006Secretory processes play an important role on the biology and life cycles of parasitic protozoa. This review focus on basic aspects, from a cell biology perspective, of... (Review)
Review
Secretory processes play an important role on the biology and life cycles of parasitic protozoa. This review focus on basic aspects, from a cell biology perspective, of the secretion of (a) micronemes, rhoptries and dense granules in members of the Apicomplexa group, where these organelles are involved in the process of protozoan penetration into the host cell, survival within the parasitophorous vacuole and subsequent egress from the host cell, (b) the Maurer's cleft in Plasmodium, a structure involved in the secretion of proteins synthesized by the intravacuolar parasite and transported through vesicles to the erythrocyte surface, (c) the secretion of macromolecules into the flagellar pocket of trypanosomatids, and (d) the secretion of proteins which make the cyst wall of Giardia and Entamoeba, with the formation of encystation vesicles.
Topics: Animals; Apicomplexa; Entamoeba; Eukaryota; Giardia; Microtubules; Organelles; Protozoan Proteins; Secretory Vesicles; Trypanosomatina
PubMed: 16710566
DOI: 10.1590/s0001-37652006000200008 -
Experimental Parasitology Sep 2017Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of... (Review)
Review
Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors.
Topics: Animals; Antiprotozoal Agents; Apicomplexa; Benzimidazoles; Humans; Imidazoles; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Protozoan Infections; Pyridines
PubMed: 28065755
DOI: 10.1016/j.exppara.2017.01.001