-
Molecular Microbiology Mar 2022Apicomplexan parasites encompass diverse pathogens for humans and animals, including the causative agents of malaria and toxoplasmosis, Plasmodium spp. and Toxoplasma... (Review)
Review
Apicomplexan parasites encompass diverse pathogens for humans and animals, including the causative agents of malaria and toxoplasmosis, Plasmodium spp. and Toxoplasma gondii. Genetic manipulation of these parasites has become central to explore parasite biology, unravel gene function and identify new targets for therapeutic strategies. Tremendous progress has been achieved over the past years with the advent of next generation sequencing and powerful genome editing methods. In particular, various methods for conditional gene expression have been developed in both Plasmodium and Toxoplasma to knockout or knockdown essential genes, or for inducible expression of master developmental regulators or mutant versions of proteins. Conditional gene expression can be achieved at three distinct levels. At the DNA level, inducible site-specific recombinases allow conditional genome editing. At the RNA level, regulation can be achieved during transcription, using stage-specific or regulatable promoters, or post-transcriptionally through alteration of mRNA stability or translation. At the protein level, several systems have been developed for inducible degradation or displacement of a protein of interest. In this review, we provide an overview of current systems for conditional control of gene expression in Plasmodium and Toxoplasma parasites, highlighting the advantages and limitations of each approach.
Topics: Animals; Gene Expression; Genes, Essential; Parasites; Plasmodium; Toxoplasma
PubMed: 34564906
DOI: 10.1111/mmi.14821 -
The Journal of Biological Chemistry Jan 2020The Apicomplexa phylum comprises diverse parasitic organisms that have evolved from a free-living ancestor. These obligate intracellular parasites exhibit versatile... (Review)
Review
The Apicomplexa phylum comprises diverse parasitic organisms that have evolved from a free-living ancestor. These obligate intracellular parasites exhibit versatile metabolic capabilities reflecting their capacity to survive and grow in different hosts and varying niches. Determined by nutrient availability, they either use their biosynthesis machineries or largely depend on their host for metabolite acquisition. Because vitamins cannot be synthesized by the mammalian host, the enzymes required for their synthesis in apicomplexan parasites represent a large repertoire of potential therapeutic targets. Here, we review recent advances in metabolic reconstruction and functional studies coupled to metabolomics that unravel the interplay between biosynthesis and salvage of vitamins and cofactors in apicomplexans. A particular emphasis is placed on , during both its acute and latent stages of infection.
Topics: Apicomplexa; Coenzymes; Host-Parasite Interactions; Humans; Metabolic Networks and Pathways; Protein Biosynthesis; Toxoplasma; Toxoplasmosis; Vitamins
PubMed: 31767680
DOI: 10.1074/jbc.AW119.008150 -
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 -
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 -
Parasitology International Jun 2015The phylum Apicomplexa includes many parasitic genera of medical and veterinary importance including Plasmodium (causative agent of malaria), Toxoplasma (toxoplasmosis),... (Review)
Review
The phylum Apicomplexa includes many parasitic genera of medical and veterinary importance including Plasmodium (causative agent of malaria), Toxoplasma (toxoplasmosis), and Babesia (babesiosis). Most of the apicomplexan parasites possess a unique, essential organelle, the apicoplast, which is a plastid without photosynthetic ability. Although the apicoplast is considered to have evolved through secondary endosymbiosis of a red alga into the common ancestral cell of apicomplexans, its evolutionary history has been under debate until recently. The apicoplast has a genome around 30-40 kb in length. Repertoire and arrangement of the apicoplast genome-encoded genes differ among apicomplexan genera, although within the genus Plasmodium these are almost conserved. Genes in the apicoplast genome may be useful markers for Plasmodium phylogeny, because these are single copy (except for the inverted repeat region) and may have more phylogenetic signal than the mitochondrial genome that have been most commonly used for Plasmodium phylogeny. This review describes recent studies concerning the evolutionary origin of the apicoplast, presents evolutionary comparison of the primary structures of apicoplast genomes from apicomplexan parasites, and summarizes recent findings of malaria phylogeny based on apicoplast genome-encoded genes.
Topics: Animals; Apicomplexa; Apicoplasts; Babesia; Evolution, Molecular; Genome, Mitochondrial; Genome, Plastid; Genome, Protozoan; Parasites; Phylogeny; Plasmodium; Toxoplasma
PubMed: 25451217
DOI: 10.1016/j.parint.2014.10.005 -
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 -
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 -
Trends in Parasitology Dec 2016Antibiotics inhibiting protein translation have long been used to treat and prevent infections by apicomplexan parasites. These compounds kill parasites by inhibiting... (Review)
Review
Antibiotics inhibiting protein translation have long been used to treat and prevent infections by apicomplexan parasites. These compounds kill parasites by inhibiting organellar translation, and most act specifically against the apicoplast, a relict plastid in apicomplexans. Drug resistance in Plasmodium and other apicomplexans dictates a need for development of novel targets. Some apicoplast inhibitors have a delayed onset of action, so they cannot replace fast-acting drugs, although they still fulfil important roles in treating and preventing infections. The plethora of bacterial-like actors in the translation machinery of parasite mitochondria and plastids presents validated targets with strong potential for selectivity. Here we discuss existing drugs that inhibit organellar translation, and explore targets that may be further exploited in antiparasitic drug design.
Topics: Antiprotozoal Agents; Apicomplexa; Apicoplasts; Drug Resistance; Mitochondria; Protein Biosynthesis
PubMed: 27793563
DOI: 10.1016/j.pt.2016.09.011 -
Biology of the Cell Jun 2020Gregarines, a polyphyletic group of apicomplexan parasites infecting mostly non-vertebrates hosts, remains poorly known at taxonomic, phylogenetic and genomic levels.... (Review)
Review
Gregarines, a polyphyletic group of apicomplexan parasites infecting mostly non-vertebrates hosts, remains poorly known at taxonomic, phylogenetic and genomic levels. However, it represents an essential group for understanding evolutionary history and adaptive capacities of apicomplexan parasites to the remarkable diversity of their hosts. Because they have a mostly extracellular lifestyle, gregarines have developed other cellular developmental forms and host-parasite interactions, compared with their much better studied apicomplexan cousins, intracellular parasites of vertebrates (Hemosporidia, Coccidia, Cryptosporidia). This review highlights the promises offered by the molecular exploration of gregarines, that have been until now left on the side of the road of the comparative -omic exploration of apicomplexan parasites. Elucidating molecular bases for both their ultrastructural, functional and behavioural similarities and differences, compared with those of the typical apicomplexan models, is expected to provide entirely novel clues on the adaptive capacities developed by Apicomplexa over evolution. A challenge remains to identify which gregarines should be explored in priority, as recent metadata from open and host-associated environments have confirmed how underestimated is our current view on true gregarine biodiversity. It is now time to turn to gregarines to widen the currently highly skewed view we have of adaptive mechanisms developed by Apicomplexa.
Topics: Animals; Apicomplexa; Biodiversity; Genomics; Metadata; Parasites; Phylogeny
PubMed: 32176937
DOI: 10.1111/boc.202000006