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Frontiers in Cellular and Infection... 2021The close-knit group of apicomplexan parasites displays a wide variety of cell division modes, which differ between parasites as well as between different life stages... (Review)
Review
The close-knit group of apicomplexan parasites displays a wide variety of cell division modes, which differ between parasites as well as between different life stages within a single parasite species. The beginning and endpoint of the asexual replication cycles is a 'zoite' harboring the defining apical organelles required for host cell invasion. However, the number of zoites produced per division round varies dramatically and can unfold in several different ways. This plasticity of the cell division cycle originates from a combination of hard-wired developmental programs modulated by environmental triggers. Although the environmental triggers and sensors differ between species and developmental stages, widely conserved secondary messengers mediate the signal transduction pathways. These environmental and genetic input integrate in division-mode specific chromosome organization and chromatin modifications that set the stage for each division mode. Cell cycle progression is conveyed by a smorgasbord of positively and negatively acting transcription factors, often acting in concert with epigenetic reader complexes, that can vary dramatically between species as well as division modes. A unique set of cell cycle regulators with spatially distinct localization patterns insert discrete check points which permit individual control and can uncouple general cell cycle progression from nuclear amplification. Clusters of expressed genes are grouped into four functional modules seen in all division modes: 1. mother cytoskeleton disassembly; 2. DNA replication and segregation (D&S); 3. karyokinesis; 4. zoite assembly. A plug-and-play strategy results in the variety of extant division modes. The timing of mother cytoskeleton disassembly is hard-wired at the species level for asexual division modes: it is either the first step, or it is the last step. In the former scenario zoite assembly occurs at the plasma membrane (external budding), and in the latter scenario zoites are assembled in the cytoplasm (internal budding). The number of times each other module is repeated can vary regardless of this first decision, and defines the modes of cell division: schizogony, binary fission, endodyogeny, endopolygeny.
Topics: Cell Cycle; Cell Division; Cell Nucleus; DNA Replication; Toxoplasma
PubMed: 33912479
DOI: 10.3389/fcimb.2021.670049 -
Innate Lymphoid Cells in Protection, Pathology, and Adaptive Immunity During Apicomplexan Infection.Frontiers in Immunology 2019Apicomplexans are a diverse and complex group of protozoan pathogens including spp., spp., spp., and spp. They infect a wide variety of hosts and are a major health... (Review)
Review
Apicomplexans are a diverse and complex group of protozoan pathogens including spp., spp., spp., and spp. They infect a wide variety of hosts and are a major health threat to humans and other animals. Innate immunity provides early control and also regulates the development of adaptive immune responses important for controlling these pathogens. Innate immune responses also contribute to immunopathology associated with these infections. Natural killer (NK) cells have been for a long time known to be potent first line effector cells in helping control protozoan infection. They provide control by producing IL-12 dependent IFNγ and killing infected cells and parasites via their cytotoxic response. Results from more recent studies indicate that NK cells could provide additional effector functions such as IL-10 and IL-17 and might have diverse roles in immunity to these pathogens. These early studies based their conclusions on the identification of NK cells to be CD3-, CD49b+, NK1.1+, and/or NKp46+ and the common accepted paradigm at that time that NK cells were one of the only lymphoid derived innate immune cells present. New discoveries have lead to major advances in understanding that NK cells are only one of several populations of innate immune cells of lymphoid origin. Common lymphoid progenitor derived innate immune cells are now known as innate lymphoid cells (ILC) and comprise three different groups, group 1, group 2, and group 3 ILC. They are a functionally heterogeneous and plastic cell population and are important effector cells in disease and tissue homeostasis. Very little is known about each of these different types of ILCs in parasitic infection. Therefore, we will review what is known about NK cells in innate immune responses during different protozoan infections. We will discuss what immune responses attributed to NK cells might be reconsidered as ILC1, 2, or 3 population responses. We will then discuss how different ILCs may impact immunopathology and adaptive immune responses to these parasites.
Topics: Adaptive Immunity; Animals; Apicomplexa; Biomarkers; Cell Plasticity; Cytokines; Host-Parasite Interactions; Humans; Immunity, Innate; Immunophenotyping; Inflammation Mediators; Lymphocyte Subsets; Plasmodium; Protozoan Infections
PubMed: 30873151
DOI: 10.3389/fimmu.2019.00196 -
Current Opinion in Microbiology Oct 2021The apicoplast is the relict of a plastid organelle found in several disease-causing apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii. In these... (Review)
Review
The apicoplast is the relict of a plastid organelle found in several disease-causing apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii. In these organisms, the organelle has lost its photosynthetic capability but harbours several fitness-conferring or essential metabolic pathways. Although maintaining the apicoplast and fuelling the metabolic pathways within requires the challenging constant import and export of numerous metabolites across its four membranes, only few apicoplast transporters have been identified to date, most of which are orphan transporters. Here we review the roles of metabolic pathways within the apicoplast and what is currently known about the few identified apicoplast metabolite transporters. We discuss what metabolites must get in and out of the apicoplast, the many transporters that are yet to be discovered, and what role these might play in parasite metabolism and as putative drug targets.
Topics: Animals; Apicomplexa; Apicoplasts; Metabolic Networks and Pathways; Parasites; Plasmodium; Toxoplasma
PubMed: 34455306
DOI: 10.1016/j.mib.2021.07.016 -
Microbiology and Molecular Biology... Dec 2018Infection is a dynamic biological process underpinned by a complex interplay between the pathogen and the host. Microbes from all domains of life, including bacteria,... (Review)
Review
Infection is a dynamic biological process underpinned by a complex interplay between the pathogen and the host. Microbes from all domains of life, including bacteria, viruses, fungi, and protozoan parasites, have the capacity to cause infection. Infection is sensed by the host, which often leads to activation of the inflammasome, a cytosolic macromolecular signaling platform that mediates the release of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and cleavage of the pore-forming protein gasdermin D, leading to pyroptosis. Host-mediated sensing of the infection occurs when pathogens inject or carry pathogen-associated molecular patterns (PAMPs) into the cytoplasm or induce damage that causes cytosolic liberation of danger-associated molecular patterns (DAMPs) in the host cell. Recognition of PAMPs and DAMPs by inflammasome sensors, including NLRP1, NLRP3, NLRC4, NAIP, AIM2, and Pyrin, initiates a cascade of events that culminate in inflammation and cell death. However, pathogens can deploy virulence factors capable of minimizing or evading host detection. This review presents a comprehensive overview of the mechanisms of microbe-induced activation of the inflammasome and the functional consequences of inflammasome activation in infectious diseases. We also explore the microbial strategies used in the evasion of inflammasome sensing at the host-microbe interaction interface.
Topics: Animals; Apicomplexa; Bacteria; Cytosol; Fungi; Host-Pathogen Interactions; Humans; Immunity, Innate; Inflammasomes; Inflammation; Pyroptosis; Viruses
PubMed: 30209070
DOI: 10.1128/MMBR.00015-18 -
Proceedings of the National Academy of... Jan 2024Parasites and their hosts are engaged in reciprocal coevolution that balances competing mechanisms of virulence, resistance, and evasion. This often leads to host...
Parasites and their hosts are engaged in reciprocal coevolution that balances competing mechanisms of virulence, resistance, and evasion. This often leads to host specificity, but genomic reassortment between different strains can enable parasites to jump host barriers and conquer new niches. In the apicomplexan parasite , genetic exchange has been hypothesized to play a prominent role in adaptation to humans. The sexual lifecycle of the parasite provides a potential mechanism for such exchange; however, the boundaries of sex are currently undefined. To explore this experimentally, we established a model for genetic crosses. Drug resistance was engineered using a mutated phenylalanyl tRNA synthetase gene and marking strains with this and the previously used Neo transgene enabled selection of recombinant progeny. This is highly efficient, and genomic recombination is evident and can be continuously monitored in real time by drug resistance, flow cytometry, and PCR mapping. Using this approach, multiple loci can now be modified with ease. We demonstrate that essential genes can be ablated by crossing a Cre recombinase driver strain with floxed strains. We further find that genetic crosses are also feasible between species. Crossing a parasite of cattle and humans, and a mouse parasite resulted in progeny with a recombinant genome derived from both species that continues to vigorously replicate sexually. These experiments have important fundamental and translational implications for the evolution of and open the door to reverse- and forward-genetic analysis of parasite biology and host specificity.
Topics: Crosses, Genetic; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Life Cycle Stages
PubMed: 38147547
DOI: 10.1073/pnas.2313210120 -
Current Opinion in Microbiology Jun 2024Apicomplexan and trypanosomatid parasites have evolved a wide range of post-transcriptional processes that allow them to replicate, differentiate, and transmit within... (Review)
Review
Apicomplexan and trypanosomatid parasites have evolved a wide range of post-transcriptional processes that allow them to replicate, differentiate, and transmit within and among multiple different tissue, host, and vector environments. In this review, we highlight the recent advances that point toward the regulatory potential of RNA modifications in mediating these processes on the coding and noncoding transcriptome throughout the life cycle of protozoan parasites. We discuss the recent technical advancements enabling the study of the 'epitranscriptome' and how parasites evolved RNA modification-mediated mechanisms adapted to their unique lifestyles.
Topics: RNA Processing, Post-Transcriptional; RNA, Protozoan; Animals; Apicomplexa; Transcriptome; Life Cycle Stages
PubMed: 38663181
DOI: 10.1016/j.mib.2024.102477 -
Malaria Journal Sep 2022Haemoproteus is a sister genus to malaria parasites (Plasmodium), which both belong to the order Haemosporida (Apicomplexa). Parasites of both genera are flourishing in... (Review)
Review
BACKGROUND
Haemoproteus is a sister genus to malaria parasites (Plasmodium), which both belong to the order Haemosporida (Apicomplexa). Parasites of both genera are flourishing in birds, however, Haemoproteus species are noticeably less investigated. This is unfortunate because knowledge about close relatives of malaria pathogens is important for better understanding the evolutionary origin and basic biological features of the entire group of haemosporidian infections. Moreover, recent findings show that Haemoproteus species can cause severe damage of various bird organs due to megalomeronts and other exo-erythrocytic stages. These haemosporidians are remarkably diverse, but remain neglected partly due to difficulties in species identification. Hundreds of Haemoproteus genetic lineages have been reported in birds, and numerous new lineages are found each year, but most remain unidentified to the species level. Numerous new Haemoproteus pathogens were described during the past 20 years. However, keys for their identification are absent. Identification of Haemoproteus species remains a difficult task and is an obstacle for better understanding of the distribution and epidemiology of these parasites. This study aimed to develop comprehensive keys for the identification of described avian Haemoproteus species using morphological features of their blood stages (gametocytes).
METHODS
Type and voucher preparations of avian Haemoproteus species were accessed in museums in Europe, Australia and the USA. Gametocytes of most described species were examined, and these data formed a background for this study. The data also were considered from published articles containing parasite species descriptions. The method of dichotomous keys was applied. The most difficult steps in the keys were accompanied with references to the corresponding parasite pictures.
RESULTS
In all, 201 published articles were included in this review. Morphological diagnostic features of gametocytes of all described Haemoproteus species were analysed and compared. Illustrated keys for identification of these parasite species were developed. Available information about the molecular characterization of Haemoproteus parasites was provided.
CONCLUSION
This review shows that 177 described species of avian Haemoproteus can be distinguished and identified in blood films using morphological characters of their gametocytes and host cells. These species were incorporated in the keys. Information about possible morphologically cryptic parasites was provided. Molecular markers are available for only 42% of the described Haemoproteus parasites, calling for researchers to fill this gap.
Topics: Animals; Birds; Haemosporida; Parasites; Phylogeny; Plasmodium
PubMed: 36123731
DOI: 10.1186/s12936-022-04235-1 -
PLoS Pathogens Dec 2023The mitochondrial electron transport chain (mETC) is a series of membrane embedded enzymatic complexes critical for energy conversion and mitochondrial metabolism. In...
The mitochondrial electron transport chain (mETC) is a series of membrane embedded enzymatic complexes critical for energy conversion and mitochondrial metabolism. In commonly studied eukaryotes, including humans and animals, complex II, also known as succinate dehydrogenase (SDH), is an essential four-subunit enzyme that acts as an entry point to the mETC, by harvesting electrons from the TCA cycle. Apicomplexa are pathogenic parasites with significant impact on human and animal health. The phylum includes Toxoplasma gondii which can cause fatal infections in immunocompromised people. Most apicomplexans, including Toxoplasma, rely on their mETC for survival, yet SDH remains largely understudied. Previous studies pointed to a divergent apicomplexan SDH with nine subunits proposed for the Toxoplasma complex, compared to four in humans. While two of the nine are homologs of the well-studied SDHA and B, the other seven have no homologs in SDHs of other systems. Moreover, SDHC and D, that anchor SDH to the membrane and participate in substrate bindings, have no homologs in Apicomplexa. Here, we validated five of the seven proposed subunits as bona fide SDH components and demonstrated their importance for SDH assembly and activity. We further find that all five subunits are important for parasite growth, and that disruption of SDH impairs mitochondrial respiration and results in spontaneous initiation of differentiation into bradyzoites. Finally, we provide evidence that the five subunits are membrane bound, consistent with their potential role in membrane anchoring, and we demonstrate that a DY motif in one of them, SDH10, is essential for complex formation and function. Our study confirms the divergent composition of Toxoplasma SDH compared to human, and starts exploring the role of the lineage-specific subunits in SDH function, paving the way for future mechanistic studies.
Topics: Animals; Humans; Succinate Dehydrogenase; Toxoplasma; Mitochondria; Mitochondrial Membranes; Citric Acid Cycle
PubMed: 38079448
DOI: 10.1371/journal.ppat.1011867 -
Antimicrobial Agents and Chemotherapy Mar 2021and , members of the phylum Apicomplexa, are significant pathogens of both humans and animals worldwide for which new and effective therapeutics are needed. Here, we...
and , members of the phylum Apicomplexa, are significant pathogens of both humans and animals worldwide for which new and effective therapeutics are needed. Here, we describe the activity of the antibiotic boromycin against and Boromycin potently inhibited intracellular proliferation of both and at half-maximal effective concentrations (EC) of 2.27 nM and 4.99 nM, respectively. Treatment of extracellular tachyzoites with 25 nM boromycin for 30 min suppressed 84% of parasite growth, but tachyzoite invasion into host cells was not affected by boromycin. Immunofluorescence of boromycin-treated showed loss of morphologically intact parasites with randomly distributed surface antigens inside the parasitophorous vacuoles. Boromycin exhibited a high selectivity for the parasites over their host cells. These results suggest that boromycin is a promising new drug candidate for treating toxoplasmosis and cryptosporidiosis.
Topics: Animals; Borates; Cryptosporidiosis; Cryptosporidium; Humans; Toxoplasma; Toxoplasmosis
PubMed: 33468470
DOI: 10.1128/AAC.01278-20 -
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