-
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 -
Trends in Parasitology Oct 2019The discovery of a plastid in apicomplexan parasites was hoped to be a watershed moment in the treatment of parasitic diseases as it revealed drug targets that are... (Review)
Review
The discovery of a plastid in apicomplexan parasites was hoped to be a watershed moment in the treatment of parasitic diseases as it revealed drug targets that are implicitly divergent from host molecular processes. Indeed, this organelle, known as the apicoplast, has since been a productive therapeutic target for pharmaceutical interventions against infections by Plasmodium, Toxoplasma, Babesia, and Theileria. However, some inhibitors of the apicoplast are restricted in their treatment utility because of their slow-kill kinetics, and this characteristic is called the delayed death effect. Here we review the recent genetic and pharmacological experiments that interrogate the causes of delayed death and explore the foundation of this phenomenon in Plasmodium and Toxoplasma parasites.
Topics: Animals; Antiparasitic Agents; Apicoplasts; Humans; Parasitic Diseases; Plasmodium; Toxoplasma
PubMed: 31427248
DOI: 10.1016/j.pt.2019.07.010 -
Experimental Parasitology Dec 2017Neospora caninum, an intracellular protozoan parasite from the phylum Apicomplexa, is the etiologic agent of neosporosis, a disease considered as a major cause of... (Review)
Review
Neospora caninum, an intracellular protozoan parasite from the phylum Apicomplexa, is the etiologic agent of neosporosis, a disease considered as a major cause of reproductive loss in cattle and neuromuscular disease in dogs. Bovine neosporosis has a great economic impact in both meat and dairy industries, related to abortion, premature culling and reduced milk yields. Although many efforts have been made to restrain bovine neosporosis, there are still no efficacious control methods. Many vaccine-development studies focused in the apicomplexan proteins involved in the adhesion and invasion of the host cell. Among these proteins, profilins have recently emerged as potential vaccine antigens or even adjuvant candidates for several diseases caused by apicomplexan parasites. Profilins bind Toll-like receptors 11 and 12 initiating MyD88 signaling, that triggers IL-12 and IFN-γ production, which may promote protection against infection. Here we summarized the state-of-the-art of novel vaccine development based on apicomplexan profilins applied as antigens or adjuvants, and delved into recent advances on N. caninum vaccines using profilin in the mouse model and in cattle.
Topics: Animals; Apicomplexa; Cattle; Cattle Diseases; Chickens; Coccidiosis; Disease Models, Animal; Mice; Neospora; Profilins; Protozoan Vaccines
PubMed: 29080789
DOI: 10.1016/j.exppara.2017.10.009 -
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 -
Current Protocols in Microbiology Feb 2018Sarcocystis neurona is a member of the important phylum Apicomplexa and the primary cause of equine protozoal myeloencephalitis (EPM). Moreover, S. neurona is the...
Sarcocystis neurona is a member of the important phylum Apicomplexa and the primary cause of equine protozoal myeloencephalitis (EPM). Moreover, S. neurona is the best-studied species in the genus Sarcocystis, one of the most successful parasite taxa, as virtually all vertebrate animals may be infected by at least one species. Consequently, scientific investigation of S. neurona will aid in the control of EPM and neurologic disease in sea mammals, while also improving our understanding of a prominent branch on the apicomplexan phylogenetic tree. These protocols describe methods that expand the capabilities to study this prominent member of the Apicomplexa. © 2018 by John Wiley & Sons, Inc.
Topics: Animals; CRISPR-Cas Systems; Encephalomyelitis; Genetic Techniques; Horse Diseases; Horses; Sarcocystis; Transfection
PubMed: 29512112
DOI: 10.1002/cpmc.48 -
Current Opinion in Microbiology Dec 2022Members of the Apicomplexa phylum are unified by an apical complex tailored for motility and host cell invasion. It includes regulated secretory organelles and a conoid... (Review)
Review
Members of the Apicomplexa phylum are unified by an apical complex tailored for motility and host cell invasion. It includes regulated secretory organelles and a conoid attached to the apical polar ring (APR) from which subpellicular microtubules emerge. In coccidia, the conoid is composed of a cone of spiraling tubulin fibers, two preconoidal rings, and two intraconoidal microtubules. The conoid extrudes through the APR in motile parasites. Recent advances in proteomics, cryo-electron tomography, super-resolution, and expansion microscopy provide a more comprehensive view of the spatial and temporal resolution of proteins belonging to the conoid subcomponents. In combination with the phenotyping of targeted mutants, the biogenesis, turnover, dynamics, and function of the conoid begin to be elucidated.
Topics: Toxoplasma; Apicomplexa; Cytoskeleton; Microtubules; Organelles
PubMed: 36332501
DOI: 10.1016/j.mib.2022.102226 -
Cellular Microbiology Jul 2020The ability of eukaryotic parasites from the phylum Apicomplexa to cause devastating diseases is predicated upon their ability to maintain faithful and precise protein... (Review)
Review
The ability of eukaryotic parasites from the phylum Apicomplexa to cause devastating diseases is predicated upon their ability to maintain faithful and precise protein trafficking mechanisms. Their parasitic life cycle depends on the trafficking of effector proteins to the infected host cell, transport of proteins to several critical organelles required for survival, as well as transport of parasite and host proteins to the digestive organelles to generate the building blocks for parasite growth. Several recent studies have shed light on the molecular mechanisms parasites utilise to transform the infected host cells, transport proteins to essential metabolic organelles and for biogenesis of organelles required for continuation of their life cycle. Here, we review key pathways of protein transport originating and branching from the endoplasmic reticulum, focusing on the essential roles of chaperones in these processes. Further, we highlight key gaps in our knowledge that prevents us from building a holistic view of protein trafficking in these deadly human pathogens.
Topics: Animals; Apicomplexa; Apicoplasts; Endoplasmic Reticulum; Humans; Malaria; Parasites; Protein Transport; Protozoan Proteins; Vacuoles
PubMed: 32388921
DOI: 10.1111/cmi.13215 -
Parasitology International Apr 2021The apicoplast is a non-photosynthetic relict plastid of Apicomplexa that evolved from a secondary symbiotic system. During its evolution, most of the genes derived from... (Review)
Review
The apicoplast is a non-photosynthetic relict plastid of Apicomplexa that evolved from a secondary symbiotic system. During its evolution, most of the genes derived from its alga ancestor were lost. Only genes involved in several valuable metabolic pathways, such as the synthesis of isoprenoid precursors, heme, and fatty acids, have been transferred to the host genome and retained to help these parasites adapt to a complex life cycle and various living environments. The biological function of an apicoplast is essential for most apicomplexan parasites. Considering their potential as drug targets, the metabolic functions of this symbiotic organelle have been intensively investigated through computational and biological means. Moreover, we know that not only organellar metabolic functions are linked with other organelles, but also their biogenesis processes have developed and evolved to tailor their biological functions and proper inheritance. Several distinct features have been found in the biogenesis process of apicoplasts. For example, the apicoplast borrows a dynamin-related protein (DrpA) from its host to implement organelle division. The autophagy system has also been repurposed for linking the apicoplast and centrosome during replication and the division process. However, many vital questions remain to be answered about how these parasites maintain and properly inherit this symbiotic organelle. Here we review our current knowledge about its biogenesis process and discuss several critical questions remaining to be answered in this field.
Topics: Apicomplexa; Apicoplasts; Organelle Biogenesis
PubMed: 33321224
DOI: 10.1016/j.parint.2020.102270 -
Fungal Biology May 2021TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfamily, characterized by the presence of the p25alpha domain. TPPPs in the...
TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfamily, characterized by the presence of the p25alpha domain. TPPPs in the strict sense are present in animals except Trichoplax adhaerens, which instead contains apicortin where a part of the p25alpha domain is combined with a DCX domain. Apicortin is absent in other animals and occurs mostly in the protozoan phylum, Apicomplexa. A strong correlation between the occurrence of p25alpha domain and that of the eukaryotic cilium/flagellum was suggested. Species of the deeper branching clades of Fungi possess flagellum but others lost it thus investigation of fungal genomes can help testing of this suggestion. Indeed, these proteins are present in early branching Fungi. Both TPPP and apicortin are present in Rozellomycota (Cryptomycota) and Chytridiomycota, TPPP in Blastocladiomycota, apicortin in Neocallimastigomycota, Monoblepharomycota and the non-flagellated Mucoromycota. Beside the "normal" TPPP occurring in animals, a special, fungal-type TPPP is also present in Fungi, in which a part of the p25alpha domain is duplicated. Dikarya, the most developed subkingdom of Fungi, lacks both flagellum and TPPPs. Thus it is strengthened that each ciliated/flagellated organism contains p25alpha domain-containing proteins while there are very few non-flagellated ones where p25alpha domain can be found.
Topics: Animals; Apicomplexa; Fungal Proteins; Fungi
PubMed: 33910677
DOI: 10.1016/j.funbio.2020.12.001 -
Protist Feb 2019Plants, fungi, and some protists possess a more branched electron transport chain in their mitochondria compared to canonical one. In these organisms, the electron... (Review)
Review
Plants, fungi, and some protists possess a more branched electron transport chain in their mitochondria compared to canonical one. In these organisms, the electron transport chain contains several rotenone-insensitive NAD(P)H dehydrogenases. Some are located on the outer surface, and others are located on the inner surface of the inner mitochondrial membrane. The putative role of these enzymes still remains elusive, but they may prevent the overreduction of the electron transport chain components and decrease the production of reaction oxygen species as a consequence. The last two decades resulted in the discovery of alternative rotenone-insensitive NAD(P)H dehydrogenases present in representatives of fungi and protozoa. The aim of this review is to gather and focus on current information concerning molecular and functional properties, regulation, and the physiological role of fungal and protozoan alternative NAD(P)H dehydrogenases.
Topics: Amoebozoa; Apicomplexa; Fungal Proteins; Fungi; Mitochondrial Proteins; NADPH Dehydrogenase; Protozoan Proteins; Trypanosoma
PubMed: 30553126
DOI: 10.1016/j.protis.2018.11.001