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Current Biology : CB Sep 2019The apicomplexans are a group of obligate animal pathogens that include Plasmodium (malaria), Toxoplasma (toxoplasmosis), and Cryptosporidium (cryptosporidiosis) [1]....
The apicomplexans are a group of obligate animal pathogens that include Plasmodium (malaria), Toxoplasma (toxoplasmosis), and Cryptosporidium (cryptosporidiosis) [1]. They are an extremely diverse and specious group but are nevertheless united by a distinctive suite of cytoskeletal and secretory structures related to infection, called the apical complex, which is used to recognize and gain entry into animal host cells. The apicomplexans are also known to have evolved from free-living photosynthetic ancestors and retain a relict plastid (the apicoplast), which is non-photosynthetic but houses a number of other essential metabolic pathways [2]. Their closest relatives include a mix of both photosynthetic algae (chromerids) and non-photosynthetic microbial predators (colpodellids) [3]. Genomic analyses of these free-living relatives have revealed a great deal about how the alga-parasite transition may have taken place, as well as origins of parasitism more generally [4]. Here, we show that, despite the surprisingly complex origin of apicomplexans from algae, this transition actually occurred at least three times independently. Using single-cell genomics and transcriptomics from diverse uncultivated parasites, we find that two genera previously classified within the Apicomplexa, Piridium and Platyproteum, form separately branching lineages in phylogenomic analyses. Both retain cryptic plastids with genomic and metabolic features convergent with apicomplexans. These findings suggest a predilection in this lineage for both the convergent loss of photosynthesis and transition to parasitism, resulting in multiple lineages of superficially similar animal parasites.
Topics: Animals; Apicomplexa; Apicoplasts; Biological Evolution; Parasites; Phylogeny
PubMed: 31422883
DOI: 10.1016/j.cub.2019.07.019 -
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 -
Cellular and Molecular Life Sciences :... Apr 2011Protistan species belonging to the phylum Apicomplexa have a non-photosynthetic secondary plastid-the apicoplast. Although its tiny genome and even the entire nuclear... (Review)
Review
Protistan species belonging to the phylum Apicomplexa have a non-photosynthetic secondary plastid-the apicoplast. Although its tiny genome and even the entire nuclear genome has been sequenced for several organisms bearing the organelle, the reason for its existence remains largely obscure. Some of the functions of the apicoplast, including housekeeping ones, are significantly different from those of other plastids, possibly due to the organelle's unique symbiotic origin.
Topics: Apicomplexa; Evolution, Molecular; Phylogeny; Plastids
PubMed: 21380560
DOI: 10.1007/s00018-011-0646-1 -
Philosophical Transactions of the Royal... Mar 2010The malaria parasite, Plasmodium falciparum, harbours a relict plastid known as the 'apicoplast'. The discovery of the apicoplast ushered in an exciting new prospect for... (Review)
Review
The malaria parasite, Plasmodium falciparum, harbours a relict plastid known as the 'apicoplast'. The discovery of the apicoplast ushered in an exciting new prospect for drug development against the parasite. The eubacterial ancestry of the organelle offers a wealth of opportunities for the development of therapeutic interventions. Morphological, biochemical and bioinformatic studies of the apicoplast have further reinforced its 'plant-like' characteristics and potential as a drug target. However, we are still not sure why the apicoplast is essential for the parasite's survival. This review explores the origins and metabolic functions of the apicoplast. In an attempt to decipher the role of the organelle within the parasite we also take a closer look at the transporters decorating the plastid to better understand the metabolic exchanges between the apicoplast and the rest of the parasite cell.
Topics: Adenosine Triphosphate; Animals; Apicomplexa; Biological Evolution; Chloroplasts; Fatty Acids; Gene Transfer, Horizontal; Heme; Humans; Iron-Sulfur Proteins; Mitochondria; Models, Biological; Plasmodium; Plastids; Protein Transport; Symbiosis; Terpenes
PubMed: 20124342
DOI: 10.1098/rstb.2009.0273 -
Eukaryotic Cell Apr 2011Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in... (Review)
Review
Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes.
Topics: Animals; Humans; Malaria, Falciparum; Mitosis; Plasmodium falciparum; Spindle Apparatus
PubMed: 21317311
DOI: 10.1128/EC.00314-10 -
Molecular and Biochemical Parasitology Oct 2012The SIR2 family of NAD(+)-dependent protein deacetylases, collectively called sirtuins, has been of central interest due to their proposed roles in life-span regulation... (Review)
Review
The SIR2 family of NAD(+)-dependent protein deacetylases, collectively called sirtuins, has been of central interest due to their proposed roles in life-span regulation and ageing. Sirtuins are one group of environment sensors of a cell interpreting external information and orchestrating internal responses at the sub-cellular level, through participation in gene regulation mechanisms. Remarkably conserved across all kingdoms of life SIR2 proteins in several protozoan parasites appear to have both conserved and intriguing unique functions. This review summarises our current knowledge of the members of the sirtuin families in Apicomplexa, including Plasmodium, and other protozoan parasites such as Trypanosoma and Leishmania. The wide diversity of processes regulated by SIR2 proteins makes them targets worthy of exploitation in anti-parasitic therapies.
Topics: Animals; Apicomplexa; Humans; Phylogeny; Protozoan Proteins; Sirtuin 2; Sirtuins
PubMed: 22906508
DOI: 10.1016/j.molbiopara.2012.08.003 -
Microbiology and Molecular Biology... Mar 1997Malaria and related apicomplexan parasites have two highly conserved organellar genomes: one is of plastid (pl) origin, and the other is mitochondrial (mt). The... (Review)
Review
Malaria and related apicomplexan parasites have two highly conserved organellar genomes: one is of plastid (pl) origin, and the other is mitochondrial (mt). The organization of both organellar DNA molecules from the human malaria parasite Plasmodium falciparum has been determined, and they have been shown to be tightly packed with genes. The 35-kb circular DNA is the smallest known vestigial plastid genome and is presumed to be functional. All but two of its recognized genes are involved with genetic expression: one of the two encodes a member of the clp family of molecular chaperones, and the other encodes a conserved protein of unknown function found both in algal plastids and in eubacterial genomes. The possible evolutionary source and intracellular location of the plDNA are discussed. The 6-kb tandemly repeated mt genome is the smallest known and codes for only three proteins (cytochrome b and two subunits of cytochrome oxidase) as well as two bizarrely fragmented rRNAs. The organization of the mt genome differs somewhat among genera. The mtDNA sequence provides information not otherwise available about the structure of apicomplexan cytochrome b as well as the unusually fragmented rRNAs. The malarial mtDNA has a phage-like replication mechanism and undergoes extensive recombination like the mtDNA of some other lower eukaryotes.
Topics: Animals; Apicomplexa; Babesia; Biological Evolution; DNA Replication; DNA, Mitochondrial; DNA, Protozoan; Genes, Protozoan; Genome; Humans; Molecular Sequence Data; Organelles; Plants; Plasmodium; Plastids; Repetitive Sequences, Nucleic Acid; Theileria; Toxoplasma; Transcription, Genetic
PubMed: 9106361
DOI: 10.1128/mmbr.61.1.1-16.1997 -
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 -
Molecular Microbiology Mar 2021Rhoptries are specialized secretory organelles found in the Apicomplexa phylum, playing a central role in the establishment of parasitism. The rhoptry content includes... (Review)
Review
Rhoptries are specialized secretory organelles found in the Apicomplexa phylum, playing a central role in the establishment of parasitism. The rhoptry content includes membranous as well as proteinaceous materials that are discharged into the host cell in a regulated fashion during parasite entry. A set of rhoptry neck proteins form a RON complex that critically participates in the moving junction formation during invasion. Some of the rhoptry bulb proteins are associated with the membranous materials and contribute to the formation of the parasitophorous vacuole membrane while others are targeted into the host cell including the nucleus to subvert cellular functions. Here, we review the recent studies on Toxoplasma and Plasmodium parasites that shed light on the key steps leading to rhoptry biogenesis, trafficking, and discharge.
Topics: Animals; Host-Parasite Interactions; Humans; Malaria; Organelle Biogenesis; Organelles; Plasmodium; Protein Transport; Protozoan Proteins; Toxoplasma; Toxoplasmosis; Virulence
PubMed: 33368727
DOI: 10.1111/mmi.14674