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Frontiers in Cellular and Infection... 2018Although apicomplexan parasites of the group Piroplasmida represent commonly identified global risks to both animals and humans, detailed knowledge of their life cycles... (Review)
Review
Although apicomplexan parasites of the group Piroplasmida represent commonly identified global risks to both animals and humans, detailed knowledge of their life cycles is surprisingly limited. Such a discrepancy results from incomplete literature reports, nomenclature disunity and recently, from large numbers of newly described species. This review intends to collate and summarize current knowledge with respect to piroplasm phylogeny. Moreover, it provides a comprehensive view of developmental events of , and representative species, focusing on uniform consensus of three consecutive phases: (i) schizogony and merogony, asexual multiplication in blood cells of the vertebrate host; (ii) gamogony, sexual reproduction inside the tick midgut, later followed by invasion of kinetes into the tick internal tissues; and (iii) sporogony, asexual proliferation in tick salivary glands resulting in the formation of sporozoites. However, many fundamental differences in this general consensus occur and this review identifies variables that should be analyzed prior to further development of specific anti-piroplasm strategies, including the attractive targeting of life cycle stages of or tick vectors.
Topics: Life Cycle Stages; Phylogeny; Piroplasmida
PubMed: 30083518
DOI: 10.3389/fcimb.2018.00248 -
Developmental and Comparative Immunology Nov 2016Fish intestinal parasites cause direct mortalities and also morbidity, poor growth, higher susceptibility to opportunistic pathogens and lower resistance to stress. This... (Review)
Review
Fish intestinal parasites cause direct mortalities and also morbidity, poor growth, higher susceptibility to opportunistic pathogens and lower resistance to stress. This review is focused on microscopic parasites (Protozoa and Metazoa) that invade the gastrointestinal tract of fish. Intracellular parasites (mainly Microsporidia and Apicomplexa) evoke almost no host immune reaction while they are concealed in the cytoplasmic and nuclear compartments, and can even use fish cells (macrophages) as Trojan horses to spread in the host. Inflammatory reaction only appears when the parasite bursts infected cells. Immunity against extracellular parasites is depicted for the myxozoans Ceratonova shasta and Enteromyxum spp. The cellular and humoral innate responses and the production of antibodies are crucial for resolving some of these myxozoonoses, but an excessive inflammatory reaction (concerted by cytokines) can become a fatal pathophysiological consequence. The local immune response plays a key role, with numerous genes more strongly regulated in the intestine than at lymphohaematopoietic organs.
Topics: Animals; Apicomplexa; Fishes; Gastrointestinal Tract; Immune Evasion; Immunity, Innate; Inflammation; Microsporidia; Microsporidiosis; Myxozoa; Parasitic Diseases, Animal; Protozoan Infections
PubMed: 26828391
DOI: 10.1016/j.dci.2016.01.014 -
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 -
Trends in Parasitology Sep 2022Apicomplexan parasites have complex metabolic networks that coordinate acquisition of metabolites by de novo synthesis and by scavenging from the host. Toxoplasma gondii... (Review)
Review
Apicomplexan parasites have complex metabolic networks that coordinate acquisition of metabolites by de novo synthesis and by scavenging from the host. Toxoplasma gondii has a wide host range and may rely on the flexibility of this metabolic network. Currently, the literature categorizes genes as essential or dispensable according to their dispensability for parasite survival under nutrient-replete in vitro conditions. However, recent studies revealed correlations between medium composition and gene essentiality. Therefore, nutrient availability in the host environment likely determines the requirement of metabolic pathways, which may redefine priorities for drug target identification in a clinical setting. Here we review the recent work characterizing some of the major Toxoplasma metabolic pathways and their functional adaptation to host nutrient content.
Topics: Metabolic Networks and Pathways; Protozoan Proteins; Toxoplasma
PubMed: 35718642
DOI: 10.1016/j.pt.2022.06.001 -
Communications Biology Nov 2022Theileria parasites are responsible for devastating cattle diseases, causing major economic losses across Africa and Asia. Theileria spp. stand apart from other...
Theileria parasites are responsible for devastating cattle diseases, causing major economic losses across Africa and Asia. Theileria spp. stand apart from other apicomplexa parasites by their ability to transform host leukocytes into immortalized, hyperproliferating, invasive cells that rapidly kill infected animals. The emergence of resistance to the theilericidal drug Buparvaquone raises the need for new anti-Theileria drugs. We developed a microscopy-based screen to reposition drugs from the open-access Medicines for Malaria Venture (MMV) Pathogen Box. We show that Trifloxystrobin (MMV688754) selectively kills lymphocytes or macrophages infected with Theileria annulata or Theileria parva parasites. Trifloxystrobin treatment reduced parasite load in vitro as effectively as Buparvaquone, with similar effects on host gene expression, cell proliferation and cell cycle. Trifloxystrobin also inhibited parasite differentiation to merozoites (merogony). Trifloxystrobin inhibition of parasite survival is independent of the parasite TaPin1 prolyl isomerase pathway. Furthermore, modeling studies predicted that Trifloxystrobin and Buparvaquone could interact distinctly with parasite Cytochrome B and we show that Trifloxystrobin was still effective against Buparvaquone-resistant cells harboring TaCytB mutations. Our study suggests that Trifloxystrobin could provide an effective alternative to Buparvaquone treatment and represents a promising candidate for future drug development against Theileria spp.
Topics: Cattle; Animals; Parasites; Antiprotozoal Agents; Theileria annulata
PubMed: 36380082
DOI: 10.1038/s42003-022-03981-x -
Nature Communications Aug 2023The phylum Apicomplexa comprises important eukaryotic parasites that invade host tissues and cells using a unique mechanism of gliding motility. Gliding is powered by...
The phylum Apicomplexa comprises important eukaryotic parasites that invade host tissues and cells using a unique mechanism of gliding motility. Gliding is powered by actomyosin motors that translocate host-attached surface adhesins along the parasite cell body. Actin filaments (F-actin) generated by Formin1 play a central role in this critical parasitic activity. However, their subcellular origin, path and ultrastructural arrangement are poorly understood. Here we used cryo-electron tomography to image motile Cryptosporidium parvum sporozoites and reveal the cellular architecture of F-actin at nanometer-scale resolution. We demonstrate that F-actin nucleates at the apically positioned preconoidal rings and is channeled into the pellicular space between the parasite plasma membrane and the inner membrane complex in a conoid extrusion-dependent manner. Within the pellicular space, filaments on the inner membrane complex surface appear to guide the apico-basal flux of F-actin. F-actin concordantly accumulates at the basal end of the parasite. Finally, analyzing a Formin1-depleted Toxoplasma gondii mutant pinpoints the upper preconoidal ring as the conserved nucleation hub for F-actin in Cryptosporidium and Toxoplasma. Together, we provide an ultrastructural model for the life cycle of F-actin for apicomplexan gliding motility.
Topics: Animals; Humans; Parasites; Actins; Cryptosporidiosis; Electron Microscope Tomography; Cryptosporidium; Actin Cytoskeleton; Toxoplasma; Protozoan Proteins
PubMed: 37558667
DOI: 10.1038/s41467-023-40520-6 -
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 -
International Journal For Parasitology Aug 2023The subclass Coccidia comprises a large group of protozoan parasites, including important pathogens of humans and animals such as Toxoplasma gondii, Neospora caninum,... (Review)
Review
The subclass Coccidia comprises a large group of protozoan parasites, including important pathogens of humans and animals such as Toxoplasma gondii, Neospora caninum, Eimeria spp., and Cystoisospora spp. Their life cycle includes a switch from asexual to sexual stages and is often restricted to a single host species. Current research on coccidian parasites focuses on cell biology and the underlying mechanisms of protein expression and trafficking in different life stages, host cell invasion and host-parasite interactions. Furthermore, novel anticoccidial drug targets are evaluated. Given the variety of research questions and the requirement to reduce and replace animal experimentation, in vitro cultivation of Coccidia needs to be further developed and refined to meet these requirements. For these purposes, established culture systems are constantly improved. In addition, new in vitro culture systems lately gained considerable importance in research on Coccidia. Well established and optimized in vitro cultures of monolayer cells can support the viability and development of parasite stages and even allow completion of the life cycle in vitro, as shown for Cystoisospora suis and Eimeria tenella. Furthermore, new three-dimensional cell culture models are used for propagation of Cryptosporidium spp. (close relatives of the coccidians), and the infection of three-dimensional organoids with T. gondii also gained popularity as the interaction between the parasite and host tissue can be studied in more detail. The latest advances in three-dimensional culture systems are organ-on-a-chip models, that to date have only been tested for T. gondii but promise to accelerate research in other coccidians. Lastly, the completion of the life cycle of C. suis and Cryptosporidium parvum was reported to continue in a host cell-free environment following the first occurrence of asexual stages. Such axenic cultures are becoming increasingly available and open new avenues for research on parasite life cycle stages and novel intervention strategies.
Topics: Animals; Humans; Parasites; Cryptosporidiosis; Cryptosporidium; Toxoplasma; Sarcocystidae; Life Cycle Stages
PubMed: 36400306
DOI: 10.1016/j.ijpara.2022.10.002 -
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