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Miroslav Oborník - One of the best experts on this subject based on the ideXlab platform.
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morphology ultrastructure and life cycle of vitrella brassicaformis n sp n gen a novel chromerid from the great barrier reef
Protist, 2012Co-Authors: Miroslav Oborník, David Modrý, Martin Lukes, Eva Cernotikovastřibrna, Jaromir Cihlař, Martina Tesařova, Eva KotabovaAbstract:Chromerida are photoautotrophic alveolates so far only isolated from corals in Australia. It has been shown that these secondary plastid-containing algae are closely related to Apicomplexan parasites and share various morphological and molecular characters with both Apicomplexa and Dinophyta. So far, the only known representative of the phylum was Chromera velia. Here we provide a formal description of another chromerid, Vitrella brassicaformis gen. et sp. nov., complemented with a detailed study on its ultrastructure, allowing insight into its life cycle. The novel alga differs significantly from the related chromerid C. velia in life cycle, morphology as well as the plastid genome. Analysis of photosynthetic pigments on the other hand demonstrate that both chromerids lack chlorophyll c, the hallmark of phototrophic chromalveolates. Based on the relatively high divergence between C. velia and V. brassicaformis, we propose their classification into distinct families Chromeraceae and Vitrellaceae. Moreover, we predict a hidden and unexplored diversity of the chromerid algae.
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tetrapyrrole synthesis of photosynthetic chromerids is likely homologous to the unusual pathway of Apicomplexan parasites
The Plant Cell, 2011Co-Authors: Ludek Koreny, Miroslav Oborník, Jan Janouskovec, Patrick J Keeling, Roman SobotkaAbstract:Most photosynthetic eukaryotes synthesize both heme and chlorophyll via a common tetrapyrrole biosynthetic pathway starting from glutamate. This pathway was derived mainly from cyanobacterial predecessor of the plastid and differs from the heme synthesis of the plastid-lacking eukaryotes. Here, we show that the coral-associated alveolate Chromera velia, the closest known photosynthetic relative to Apicomplexa, possesses a tetrapyrrole pathway that is homologous to the unusual pathway of Apicomplexan parasites. We also demonstrate that, unlike other eukaryotic phototrophs, Chromera synthesizes chlorophyll from glycine and succinyl-CoA rather than glutamate. Our data shed light on the evolution of the heme biosynthesis in parasitic Apicomplexa and photosynthesis-related biochemical processes in their ancestors.
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morphology and ultrastructure of multiple life cycle stages of the photosynthetic relative of Apicomplexa chromera velia
Protist, 2011Co-Authors: Miroslav Oborník, Jan Janouskovec, Patrick J Keeling, Marie Vancova, Dehua Lai, Julius LukesAbstract:Chromera veliais a photosynthetic alga with a secondary plastid that represents the closest known photosynthetic relative of the Apicomplexan parasites. The original description of this organism was based on brownish, immotile coccoid cells, which is the predominating stage ofC. veliain the culture. Here we provide a detailed light and electron microscopy description of coccoid cells ofC. veliaand a previously undocumented bi-flagellated stage that is highly motile and moves in a characteristic zig-zag pattern. Transformation from a coccoid into a flagellate stage occurs in exponentially growing cultures, and is accelerated by exposure to light. TheC. veliacells contain a pseudoconoid, which is likely homologous to the corresponding structure in the apical complex of Apicomplexa, cortical alveoli subtended by subpellicular microtubules, mitochondrion with tubular cristae, a micropyle, and a distinctive chromerosome, an apparently novel type of extrusion organelle. Ultrastructural analysis of the flagellate supports its close association with colpodellids and Apicomplexans and provides important insight into their evolution.
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evolution of the apicoplast and its hosts from heterotrophy to autotrophy and back again
International Journal for Parasitology, 2009Co-Authors: Miroslav Oborník, Jan Janouskovec, Tomas Chrudimský, Julius LukesAbstract:The photosynthetic origin of Apicomplexan parasites was proposed upon the discovery of a reduced non-photosynthetic plastid termed the apicoplast in their cells. Although it is clear that the apicoplast has evolved through a secondary endosymbiosis, its particular origin within the red or green plastid lineage remains controversial. The recent discovery of Chromera velia, the closest known photosynthetic relative to Apicomplexan parasites, sheds new light on the evolutionary history of alveolate plastids. Here we review our knowledge on the evolutionary history of Apicomplexa and particularly their plastids, with a focus on the pathway by which they evolved from free-living heterotrophs through photoautotrophs to omnipresent obligatory intracellular parasites. New sequences from C. velia (histones H2A, H2B; GAPDH, TufA) and phylogenetic analyses are also presented and discussed here.
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a photosynthetic alveolate closely related to Apicomplexan parasites
Nature, 2008Co-Authors: Robert Moore, Miroslav Oborník, Jan Janouskovec, Tomas Chrudimský, Marie Vancova, David H Green, Simon W Wright, Noel W Davies, Christopher J S Bolch, Kirsten HeimannAbstract:Many parasitic Apicomplexa, such as Plasmodium falciparum, contain an unpigmented chloroplast remnant termed the apicoplast, which is a target for malaria treatment. However, no close relative of Apicomplexans with a functional photosynthetic plastid has yet been described. Here we describe a newly cultured organism that has ultrastructural features typical for alveolates, is phylogenetically related to Apicomplexans, and contains a photosynthetic plastid. The plastid is surrounded by four membranes, is pigmented by chlorophyll a, and uses the codon UGA to encode tryptophan in the psbA gene. This genetic feature has been found only in coccidian apicoplasts and various mitochondria. The UGA-Trp codon and phylogenies of plastid and nuclear ribosomal RNA genes indicate that the organism is the closest known photosynthetic relative to Apicomplexan parasites and that its plastid shares an origin with the apicoplasts. The discovery of this organism provides a powerful model with which to study the evolution of parasitism in Apicomplexa.
Patrick J Keeling - One of the best experts on this subject based on the ideXlab platform.
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phylogenomics identifies a new major subgroup of Apicomplexans marosporida class nov with extreme apicoplast genome reduction
Genome Biology and Evolution, 2021Co-Authors: Varsha Mathur, Waldan K Kwong, Filip Husnik, Nicholas A T Irwin, Arni Kristmundsson, C Gestal, Mark A Freeman, Patrick J KeelingAbstract:The phylum Apicomplexa consists largely of obligate animal parasites that include the causative agents of human diseases such as malaria. Apicomplexans have also emerged as models to study the evolution of nonphotosynthetic plastids, as they contain a relict chloroplast known as the apicoplast. The apicoplast offers important clues into how Apicomplexan parasites evolved from free-living ancestors and can provide insights into reductive organelle evolution. Here, we sequenced the transcriptomes and apicoplast genomes of three deep-branching Apicomplexans, Margolisiella islandica, Aggregata octopiana, and Merocystis kathae. Phylogenomic analyses show that these taxa, together with Rhytidocystis, form a new lineage of Apicomplexans that is sister to the Coccidia and Hematozoa (the lineages including most medically significant taxa). Members of this clade retain plastid genomes and the canonical Apicomplexan plastid metabolism. However, the apicoplast genomes of Margolisiella and Rhytidocystis are the most reduced of any apicoplast, are extremely GC-poor, and have even lost genes for the canonical plastidial RNA polymerase. This new lineage of Apicomplexans, for which we propose the class Marosporida class nov., occupies a key intermediate position in the Apicomplexan phylogeny, and adds a new complexity to the models of stepwise reductive evolution of genome structure and organelle function in these parasites.
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tetrapyrrole synthesis of photosynthetic chromerids is likely homologous to the unusual pathway of Apicomplexan parasites
The Plant Cell, 2011Co-Authors: Ludek Koreny, Miroslav Oborník, Jan Janouskovec, Patrick J Keeling, Roman SobotkaAbstract:Most photosynthetic eukaryotes synthesize both heme and chlorophyll via a common tetrapyrrole biosynthetic pathway starting from glutamate. This pathway was derived mainly from cyanobacterial predecessor of the plastid and differs from the heme synthesis of the plastid-lacking eukaryotes. Here, we show that the coral-associated alveolate Chromera velia, the closest known photosynthetic relative to Apicomplexa, possesses a tetrapyrrole pathway that is homologous to the unusual pathway of Apicomplexan parasites. We also demonstrate that, unlike other eukaryotic phototrophs, Chromera synthesizes chlorophyll from glycine and succinyl-CoA rather than glutamate. Our data shed light on the evolution of the heme biosynthesis in parasitic Apicomplexa and photosynthesis-related biochemical processes in their ancestors.
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Identification of plant-like galactolipids in Chromera velia, a photosynthetic relative of malaria parasites.
Journal of Biological Chemistry, 2011Co-Authors: Cyrille Y Botte, Eric Maréchal, Yoshiki Yamaryo-botté, Jan Janouskovec, Thusita Rupasinghe, Patrick J Keeling, Paul Crellin, Ross L Coppel, Malcolm J Mcconville, Geoffrey I McfaddenAbstract:Apicomplexa are protist parasites that include Plasmodium spp., the causative agents of malaria, and Toxoplasma gondii, responsible for toxoplasmosis. Most Apicomplexa possess a relict plastid, the apicoplast, which was acquired by secondary endosymbiosis of a red alga. Despite being nonphotosynthetic, the apicoplast is otherwise metabolically similar to algal and plant plastids and is essential for parasite survival. Previous studies of Toxoplasma gondii identified membrane lipids with some structural features of plastid galactolipids, the major plastid lipid class. However, direct evidence for the plant-like enzymes responsible for galactolipid synthesis in Apicomplexan parasites has not been obtained. Chromera velia is an Apicomplexan relative recently discovered in Australian corals. C. velia retains a photosynthetic plastid, providing a unique model to study the evolution of the apicoplast. Here, we report the unambiguous presence of plant-like monogalactosyldiacylglycerol and digalactosyldiacylglycerol in C. velia and localize digalactosyldiacylglycerol to the plastid. We also provide evidence for a plant-like biosynthesis pathway and identify candidate galactosyltranferases responsible for galactolipid synthesis. Our study provides new insights in the evolution of these important enzymes in plastid-containing eukaryotes and will help reconstruct the evolution of glycerolipid metabolism in important parasites such as Plasmodium and Toxoplasma.
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morphology and ultrastructure of multiple life cycle stages of the photosynthetic relative of Apicomplexa chromera velia
Protist, 2011Co-Authors: Miroslav Oborník, Jan Janouskovec, Patrick J Keeling, Marie Vancova, Dehua Lai, Julius LukesAbstract:Chromera veliais a photosynthetic alga with a secondary plastid that represents the closest known photosynthetic relative of the Apicomplexan parasites. The original description of this organism was based on brownish, immotile coccoid cells, which is the predominating stage ofC. veliain the culture. Here we provide a detailed light and electron microscopy description of coccoid cells ofC. veliaand a previously undocumented bi-flagellated stage that is highly motile and moves in a characteristic zig-zag pattern. Transformation from a coccoid into a flagellate stage occurs in exponentially growing cultures, and is accelerated by exposure to light. TheC. veliacells contain a pseudoconoid, which is likely homologous to the corresponding structure in the apical complex of Apicomplexa, cortical alveoli subtended by subpellicular microtubules, mitochondrion with tubular cristae, a micropyle, and a distinctive chromerosome, an apparently novel type of extrusion organelle. Ultrastructural analysis of the flagellate supports its close association with colpodellids and Apicomplexans and provides important insight into their evolution.
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nuclear encoded plastid targeted genes suggest a single common origin for Apicomplexan and dinoflagellate plastids
Molecular Biology and Evolution, 2001Co-Authors: Naomi M Fast, David S. Roos, Jessica C Kissinger, Patrick J KeelingAbstract:: The phylum Apicomplexa encompasses a large number of intracellular protozoan parasites, including the causative agents of malaria (Plasmodium), toxoplasmosis (Toxoplasma), and many other human and animal diseases. Apicomplexa have recently been found to contain a relic, nonphotosynthetic plastid that has attracted considerable interest as a possible target for therapeutics. This plastid is known to have been acquired by secondary endosymbiosis, but when this occurred and from which type of alga it was acquired remain uncertain. Based on the molecular phylogeny of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes, we provide evidence that the Apicomplexan plastid is homologous to plastids found in dinoflagellates-close relatives of Apicomplexa that contain secondary plastids of red algal origin. Surprisingly, Apicomplexan and dinoflagellate plastid-targeted GAPDH sequences were also found to be closely related to the plastid-targeted GAPDH genes of heterokonts and cryptomonads, two other groups that contain secondary plastids of red algal origin. These results address several outstanding issues: (1) Apicomplexan and dinoflagellate plastids appear to be the result of a single endosymbiotic event which occurred relatively early in eukaryotic evolution, also giving rise to the plastids of heterokonts and perhaps cryptomonads; (2) Apicomplexan plastids are derived from a red algal ancestor; and (3) the ancestral state of Apicomplexan parasites was photosynthetic.
Jan Janouskovec - One of the best experts on this subject based on the ideXlab platform.
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tetrapyrrole synthesis of photosynthetic chromerids is likely homologous to the unusual pathway of Apicomplexan parasites
The Plant Cell, 2011Co-Authors: Ludek Koreny, Miroslav Oborník, Jan Janouskovec, Patrick J Keeling, Roman SobotkaAbstract:Most photosynthetic eukaryotes synthesize both heme and chlorophyll via a common tetrapyrrole biosynthetic pathway starting from glutamate. This pathway was derived mainly from cyanobacterial predecessor of the plastid and differs from the heme synthesis of the plastid-lacking eukaryotes. Here, we show that the coral-associated alveolate Chromera velia, the closest known photosynthetic relative to Apicomplexa, possesses a tetrapyrrole pathway that is homologous to the unusual pathway of Apicomplexan parasites. We also demonstrate that, unlike other eukaryotic phototrophs, Chromera synthesizes chlorophyll from glycine and succinyl-CoA rather than glutamate. Our data shed light on the evolution of the heme biosynthesis in parasitic Apicomplexa and photosynthesis-related biochemical processes in their ancestors.
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Identification of plant-like galactolipids in Chromera velia, a photosynthetic relative of malaria parasites.
Journal of Biological Chemistry, 2011Co-Authors: Cyrille Y Botte, Eric Maréchal, Yoshiki Yamaryo-botté, Jan Janouskovec, Thusita Rupasinghe, Patrick J Keeling, Paul Crellin, Ross L Coppel, Malcolm J Mcconville, Geoffrey I McfaddenAbstract:Apicomplexa are protist parasites that include Plasmodium spp., the causative agents of malaria, and Toxoplasma gondii, responsible for toxoplasmosis. Most Apicomplexa possess a relict plastid, the apicoplast, which was acquired by secondary endosymbiosis of a red alga. Despite being nonphotosynthetic, the apicoplast is otherwise metabolically similar to algal and plant plastids and is essential for parasite survival. Previous studies of Toxoplasma gondii identified membrane lipids with some structural features of plastid galactolipids, the major plastid lipid class. However, direct evidence for the plant-like enzymes responsible for galactolipid synthesis in Apicomplexan parasites has not been obtained. Chromera velia is an Apicomplexan relative recently discovered in Australian corals. C. velia retains a photosynthetic plastid, providing a unique model to study the evolution of the apicoplast. Here, we report the unambiguous presence of plant-like monogalactosyldiacylglycerol and digalactosyldiacylglycerol in C. velia and localize digalactosyldiacylglycerol to the plastid. We also provide evidence for a plant-like biosynthesis pathway and identify candidate galactosyltranferases responsible for galactolipid synthesis. Our study provides new insights in the evolution of these important enzymes in plastid-containing eukaryotes and will help reconstruct the evolution of glycerolipid metabolism in important parasites such as Plasmodium and Toxoplasma.
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morphology and ultrastructure of multiple life cycle stages of the photosynthetic relative of Apicomplexa chromera velia
Protist, 2011Co-Authors: Miroslav Oborník, Jan Janouskovec, Patrick J Keeling, Marie Vancova, Dehua Lai, Julius LukesAbstract:Chromera veliais a photosynthetic alga with a secondary plastid that represents the closest known photosynthetic relative of the Apicomplexan parasites. The original description of this organism was based on brownish, immotile coccoid cells, which is the predominating stage ofC. veliain the culture. Here we provide a detailed light and electron microscopy description of coccoid cells ofC. veliaand a previously undocumented bi-flagellated stage that is highly motile and moves in a characteristic zig-zag pattern. Transformation from a coccoid into a flagellate stage occurs in exponentially growing cultures, and is accelerated by exposure to light. TheC. veliacells contain a pseudoconoid, which is likely homologous to the corresponding structure in the apical complex of Apicomplexa, cortical alveoli subtended by subpellicular microtubules, mitochondrion with tubular cristae, a micropyle, and a distinctive chromerosome, an apparently novel type of extrusion organelle. Ultrastructural analysis of the flagellate supports its close association with colpodellids and Apicomplexans and provides important insight into their evolution.
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evolution of the apicoplast and its hosts from heterotrophy to autotrophy and back again
International Journal for Parasitology, 2009Co-Authors: Miroslav Oborník, Jan Janouskovec, Tomas Chrudimský, Julius LukesAbstract:The photosynthetic origin of Apicomplexan parasites was proposed upon the discovery of a reduced non-photosynthetic plastid termed the apicoplast in their cells. Although it is clear that the apicoplast has evolved through a secondary endosymbiosis, its particular origin within the red or green plastid lineage remains controversial. The recent discovery of Chromera velia, the closest known photosynthetic relative to Apicomplexan parasites, sheds new light on the evolutionary history of alveolate plastids. Here we review our knowledge on the evolutionary history of Apicomplexa and particularly their plastids, with a focus on the pathway by which they evolved from free-living heterotrophs through photoautotrophs to omnipresent obligatory intracellular parasites. New sequences from C. velia (histones H2A, H2B; GAPDH, TufA) and phylogenetic analyses are also presented and discussed here.
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a photosynthetic alveolate closely related to Apicomplexan parasites
Nature, 2008Co-Authors: Robert Moore, Miroslav Oborník, Jan Janouskovec, Tomas Chrudimský, Marie Vancova, David H Green, Simon W Wright, Noel W Davies, Christopher J S Bolch, Kirsten HeimannAbstract:Many parasitic Apicomplexa, such as Plasmodium falciparum, contain an unpigmented chloroplast remnant termed the apicoplast, which is a target for malaria treatment. However, no close relative of Apicomplexans with a functional photosynthetic plastid has yet been described. Here we describe a newly cultured organism that has ultrastructural features typical for alveolates, is phylogenetically related to Apicomplexans, and contains a photosynthetic plastid. The plastid is surrounded by four membranes, is pigmented by chlorophyll a, and uses the codon UGA to encode tryptophan in the psbA gene. This genetic feature has been found only in coccidian apicoplasts and various mitochondria. The UGA-Trp codon and phylogenies of plastid and nuclear ribosomal RNA genes indicate that the organism is the closest known photosynthetic relative to Apicomplexan parasites and that its plastid shares an origin with the apicoplasts. The discovery of this organism provides a powerful model with which to study the evolution of parasitism in Apicomplexa.
David S. Roos - One of the best experts on this subject based on the ideXlab platform.
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cryptic organelle homology in Apicomplexan parasites insights from evolutionary cell biology
Current Opinion in Microbiology, 2013Co-Authors: Christen M. Klinger, David S. Roos, Ellen R R Nisbet, Dinkorma T Ouologuem, Joel B. DacksAbstract:The economic and clinical significance of Apicomplexan parasites drives interest in their many evolutionary novelties. Distinctive intracellular organelles play key roles in parasite motility, invasion, metabolism, and replication, and understanding their relationship with the organelles of better-studied eukaryotic systems suggests potential targets for therapeutic intervention. Recent work has demonstrated divergent aspects of canonical eukaryotic components in the Apicomplexa, including Golgi bodies and mitochondria. The apicoplast is a relict plastid of secondary endosymbiotic origin, harboring metabolic pathways distinct from those of host species. The inner membrane complex (IMC) is derived from the cortical alveoli defining the superphylum Alveolata, but in Apicomplexans functions in parasite motility and replication. Micronemes and rhoptries are associated with establishment of the intracellular niche, and define the apical complex for which the phylum is named. Morphological, cell biological and molecular evidence strongly suggest that these organelles are derived from the endocytic pathway.
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daughter cell assembly in the protozoan parasite toxoplasma gondii
Molecular Biology of the Cell, 2002Co-Authors: Tara Mann, David S. Roos, Boris Striepen, Con J Beckers, John M MurrayAbstract:The phylum Apicomplexa includes thousands of species of obligate intracellular parasites, many of which are significant human and/or animal pathogens. Parasites in this phylum replicate by assembling daughters within the mother, using a cytoskeletal and membranous scaffolding termed the inner membrane complex. Most Apicomplexan parasites, including Plasmodium sp. (which cause malaria), package many daughters within a single mother during mitosis, whereas Toxoplasma gondii typically packages only two. The comparatively simple pattern of T. gondii cell division, combined with its molecular genetic and cell biological accessibility, makes this an ideal system to study parasite cell division. A recombinant fusion between the fluorescent protein reporter YFP and the inner membrane complex protein IMC1 has been exploited to examine daughter scaffold formation in T. gondii. Time-lapse video microscopy permits the entire cell cycle of these parasites to be visualized in vivo. In addition to replication via endodyogeny (packaging two parasites at a time), T. gondii is also capable of forming multiple daughters, suggesting fundamental similarities between cell division in T. gondii and other Apicomplexan parasites.
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nuclear encoded plastid targeted genes suggest a single common origin for Apicomplexan and dinoflagellate plastids
Molecular Biology and Evolution, 2001Co-Authors: Naomi M Fast, David S. Roos, Jessica C Kissinger, Patrick J KeelingAbstract:: The phylum Apicomplexa encompasses a large number of intracellular protozoan parasites, including the causative agents of malaria (Plasmodium), toxoplasmosis (Toxoplasma), and many other human and animal diseases. Apicomplexa have recently been found to contain a relic, nonphotosynthetic plastid that has attracted considerable interest as a possible target for therapeutics. This plastid is known to have been acquired by secondary endosymbiosis, but when this occurred and from which type of alga it was acquired remain uncertain. Based on the molecular phylogeny of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes, we provide evidence that the Apicomplexan plastid is homologous to plastids found in dinoflagellates-close relatives of Apicomplexa that contain secondary plastids of red algal origin. Surprisingly, Apicomplexan and dinoflagellate plastid-targeted GAPDH sequences were also found to be closely related to the plastid-targeted GAPDH genes of heterokonts and cryptomonads, two other groups that contain secondary plastids of red algal origin. These results address several outstanding issues: (1) Apicomplexan and dinoflagellate plastids appear to be the result of a single endosymbiotic event which occurred relatively early in eukaryotic evolution, also giving rise to the plastids of heterokonts and perhaps cryptomonads; (2) Apicomplexan plastids are derived from a red algal ancestor; and (3) the ancestral state of Apicomplexan parasites was photosynthetic.
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Shikimate pathway in Apicomplexan parasites
Nature, 1999Co-Authors: Patrick J Keeling, Ross F. Waller, David S. Roos, Jeffrey D. Palmer, Robert G. K. Donald, Geoffrey I McfaddenAbstract:The discovery of plastids in Apicomplexan parasites1,3 raised the possibility that these organelles might harbour plastid-specific metabolic activities that could be blocked by therapeutic agents. Ideally, these agents would inhibit the parasites without harming their vertebrate hosts. Roberts et al.4 have made the promising dicovery that Apicomplexa are sensitive to the herbicide glyphosate (better known by its trade names of RoundUp, Zero or Tumbleweed), which is an inhibitor of the enzyme 5-enopyruvyl shikimate 3-phosphate synthase. They suggested that production of aromatic amino acids by the pathway involving this enzyme, the shikimate pathway, might be an essential function of the Apicomplexan plastid, but here we present evidence that this pathway actually operates in the cytosol of Apicomplexa.
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a plastid organelle as a drug target in Apicomplexan parasites
Nature, 1997Co-Authors: Maria E Fichera, David S. RoosAbstract:Parasites of the phylum Apicomplexa include many important human and veterinary pathogens such as Plasmodium (malaria), Toxoplasma (a leading opportunistic infection associated with AIDS and congenital neurological birth defects), and Eimeria (an economically significant disease of poultry and cattle)1,2,3,4. Recent studies have identified an unusual organelle in these parasites5,6,7: a plastid that appears to have been acquired by secondary endosymbiosis of a green alga7. Here we show that replication of the Apicomplexan plastid (apicoplast) genome in Toxoplasma gondii tachyzoites can be specifically inhibited using ciprofloxacin, and that this inhibition blocks parasite replication. Moreover, parasite death occurs with peculiar kinetics that are identical to those observed after exposure to clindamycin and macrolide antibiotics8,9, which have been proposed to target protein synthesis in the apicoplast9,10. Conversely, clindamycin (and functionally related compounds) immediately inhibits plastid replication upon drug application—the earliest effect so far described for these antibiotics. Our results directly link apicoplast function with parasite survival, validating this intriguing organelle as an effective target for parasiticidal drug design.
Christian Doerig - One of the best experts on this subject based on the ideXlab platform.
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protein kinases of the human malaria parasite plasmodium falciparum the kinome of a divergent eukaryote
BMC Genomics, 2004Co-Authors: Pauline Ward, Leila Equinet, Jeremy Packer, Christian DoerigAbstract:BACKGROUND: Malaria, caused by the parasitic protist Plasmodium falciparum, represents a major public health problem in the developing world. The P. falciparum genome has been sequenced, which provides new opportunities for the identification of novel drug targets. Eukaryotic protein kinases (ePKs) form a large family of enzymes with crucial roles in most cellular processes; hence malarial ePKS represent potential drug targets. We report an exhaustive analysis of the P. falciparum genomic database (PlasmoDB) aimed at identifying and classifying all ePKs in this organism. RESULTS: Using a variety of bioinformatics tools, we identified 65 malarial ePK sequences and constructed a phylogenetic tree to position these sequences relative to the seven established ePK groups. Predominant features of the tree were: (i) that several malarial sequences did not cluster within any of the known ePK groups; (ii) that the CMGC group, whose members are usually involved in the control of cell proliferation, had the highest number of malarial ePKs; and (iii) that no malarial ePK clustered with the tyrosine kinase (TyrK) or STE groups, pointing to the absence of three-component MAPK modules in the parasite. A novel family of 20 ePK-related sequences was identified and called FIKK, on the basis of a conserved amino acid motif. The FIKK family seems restricted to Apicomplexa, with 20 members in P. falciparum and just one member in some other Apicomplexan species. CONCLUSION: The considerable phylogenetic distance between Apicomplexa and other Eukaryotes is reflected by profound divergences between the kinome of malaria parasites and that of yeast or mammalian cells.
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protein kinases of the human malaria parasite plasmodium falciparum the kinome of a divergent eukaryote
BMC Genomics, 2004Co-Authors: Pauline Ward, Leila Equinet, Jeremy Packer, Christian DoerigAbstract:Malaria, caused by the parasitic protist Plasmodium falciparum, represents a major public health problem in the developing world. The P. falciparum genome has been sequenced, which provides new opportunities for the identification of novel drug targets. Eukaryotic protein kinases (ePKs) form a large family of enzymes with crucial roles in most cellular processes; hence malarial ePKS represent potential drug targets. We report an exhaustive analysis of the P. falciparum genomic database (PlasmoDB) aimed at identifying and classifying all ePKs in this organism. Using a variety of bioinformatics tools, we identified 65 malarial ePK sequences and constructed a phylogenetic tree to position these sequences relative to the seven established ePK groups. Predominant features of the tree were: (i) that several malarial sequences did not cluster within any of the known ePK groups; (ii) that the CMGC group, whose members are usually involved in the control of cell proliferation, had the highest number of malarial ePKs; and (iii) that no malarial ePK clustered with the tyrosine kinase (TyrK) or STE groups, pointing to the absence of three-component MAPK modules in the parasite. A novel family of 20 ePK-related sequences was identified and called FIKK, on the basis of a conserved amino acid motif. The FIKK family seems restricted to Apicomplexa, with 20 members in P. falciparum and just one member in some other Apicomplexan species. The considerable phylogenetic distance between Apicomplexa and other Eukaryotes is reflected by profound divergences between the kinome of malaria parasites and that of yeast or mammalian cells.