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Journal of Microbiology (Seoul, Korea) Apr 2017Malaria has been present since ancient time and remains a major global health problem in developing countries. Plasmodium falciparum belongs to the phylum Apicomplexan,... (Review)
Review
Malaria has been present since ancient time and remains a major global health problem in developing countries. Plasmodium falciparum belongs to the phylum Apicomplexan, largely contain disease-causing parasites and characterized by the presence of apicoplast. It is a very essential organelle of P. falciparum responsible for the synthesis of key molecules required for the growth of the parasite. Indispensable nature of apicoplast makes it a potential drug target. Calcium signaling is important in the establishment of malaria parasite inside the host. It has been involved in invasion and egress of merozoites during the asexual life cycle of the parasite. Calcium signaling also regulates apicoplast metabolism. Therefore, in this review, we will focus on the role of apicoplast in malaria biology and its metabolic regulation through Ca signaling.
Topics: Apicoplasts; Calcium; Calcium Signaling; Gene Expression Regulation; Plasmodium falciparum
PubMed: 28251546
DOI: 10.1007/s12275-017-6525-1 -
Malaria Journal Mar 2019While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the... (Review)
Review
While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the gametocyte sex ratio contribution to this process still remains a relevant research question. The present review discusses the biology of sex determination in P. falciparum, the underlying host and parasite factors, the sex specific susceptibility to drugs, the effect of sex ratio dynamics on malaria parasite transmission and the development of gametocyte sex specific diagnosis tools. Despite the inherent differences across several studies and approaches, the emerging picture highlights a potentially relevant contribution of the P. falciparum gametocyte sex ratio in the modulation of malaria parasite transmission. The increasing availability of molecular methods to measure gametocyte sex ratio will enable evaluation of important parameters, such as the impact of drug treatment on gametocyte sex ratio in vitro and in vivo as well as the changes of gametocyte sex ratios in natural infections, key steps towards elucidating how these parameters affect parasite infectiousness to the mosquito vectors.
Topics: Disease Transmission, Infectious; Female; Genotype; Humans; Malaria, Falciparum; Male; Phenotype; Plasmodium falciparum
PubMed: 30866941
DOI: 10.1186/s12936-019-2707-0 -
Genome Biology Oct 2002The human malaria parasite Plasmodium falciparum, one of the world's most devastating pathogens, has an astonishing array of sequences and genes that play key roles in... (Review)
Review
The human malaria parasite Plasmodium falciparum, one of the world's most devastating pathogens, has an astonishing array of sequences and genes that play key roles in pathogenesis and immune evasion. We must understand the functions of these elements if the chronicity and unpredictable virulence of Plasmodium is to be explained.
Topics: Animals; Humans; Plasmodium falciparum; Virulence
PubMed: 12441004
DOI: 10.1186/gb-2002-3-11-reviews1031 -
Chemical Reviews Mar 2012
Review
Topics: Animals; Antiprotozoal Agents; Humans; Molecular Targeted Therapy; Plasmodium falciparum; Plastids
PubMed: 22026508
DOI: 10.1021/cr200258w -
Current Opinion in Microbiology Dec 2020For malaria parasites regulating sexual commitment, the frequency with which asexual bloodstream forms differentiate into non-replicative male and female gametocytes, is... (Review)
Review
For malaria parasites regulating sexual commitment, the frequency with which asexual bloodstream forms differentiate into non-replicative male and female gametocytes, is critical because asexual replication is required to maintain a persistent infection of the human host while gametocytes are essential for infection of the mosquito vector and transmission. Here, we describe recent advances in understanding of the regulatory mechanisms controlling this key developmental decision. These include new insights into the mechanistic roles of the transcriptional master switch AP2-G and the epigenetic modulator GDV1, as well as the identification of defined metabolic signals that modulate their activity. Many of these metabolites are linked to parasite phospholipid biogenesis and we propose a model linking this pathway to the epigenetic regulation underlying sexual commitment in P. falciparum.
Topics: Animals; Epigenesis, Genetic; Germ Cells; Humans; Malaria, Falciparum; Plasmodium falciparum; Reproduction
PubMed: 33053503
DOI: 10.1016/j.mib.2020.09.004 -
Biochemical Society Transactions Jun 2010Malaria, which is caused by species of the parasite genus Plasmodium, remains a major global health problem. A vestigial plastid homologous with the chloroplasts of... (Review)
Review
Malaria, which is caused by species of the parasite genus Plasmodium, remains a major global health problem. A vestigial plastid homologous with the chloroplasts of plants and algae was discovered in malaria and related parasites from the phylum Apicomplexa and has radically changed our view of the evolutionary origins of these disease-causing protists. We now recognize that this large group of parasites had a photosynthetic ancestry and were converted into parasitism early in the evolution of animals. Apicomplexans have probably been parasitizing the animal kingdom for more than 500 million years. The relic plastid persists in most apicomplexans and is an essential component. Perturbation of apicoplast function or inheritance results in parasite death, making the organelle a promising target for chemotherapy. Plastids, including those of malaria parasites, are essentially reduced endosymbiotic bacteria living inside a eukaryotic host. This means that plastids have bacterial-type metabolic pathways and housekeeping processes, all of which are vulnerable to antibacterial compounds. Indeed, many antibacterials kill malaria parasites by blocking essential processes in the plastid. Furthermore, a range of herbicides that target plastid metabolism of undesired plants are also parasiticidal, making them potential new leads for antimalarial drugs. In the present review, we examine the evolutionary origins of the malaria parasite's plastid by endosymbiosis and outline the recent findings on how the organelle imports nuclear-encoded proteins through a set of translocation machineries in the membranes that bound the organelle.
Topics: Animals; Biological Evolution; Humans; Malaria, Falciparum; Phylogeny; Plasmodium falciparum; Plastids; Symbiosis
PubMed: 20491664
DOI: 10.1042/BST0380775 -
Trends in Parasitology Oct 2009Recent studies of Plasmodium falciparum isolated directly from infected patients indicate that alternative parasite biological states occur in the natural host that are... (Review)
Review
Recent studies of Plasmodium falciparum isolated directly from infected patients indicate that alternative parasite biological states occur in the natural host that are not observed with in vitro cultivated parasites. Variation in host substrates, immune responses and other factors probably induce modifications in parasite biology. These biological states could have important implications for pathogenesis, transmission and therapy. We review the differences between P. falciparum in vitro culture systems and in vivo host environments, as well as evidence that host conditions can alter pathogen biology. For select biological questions, the incorporation of naturally occurring conditions into in vitro experimental manipulation of microbes may provide novel insight into pathogen biology.
Topics: Animals; Blood Physiological Phenomena; Culture Media; Erythrocytes; Malaria, Falciparum; Mice; Parasitology; Plasmodium falciparum
PubMed: 19747879
DOI: 10.1016/j.pt.2009.07.005 -
Malaria Journal Aug 2020The emergence of artemisinin-resistant malaria parasites highlights the need for novel drugs and their targets. Alkylation of purine bases can hinder DNA replication and...
BACKGROUND
The emergence of artemisinin-resistant malaria parasites highlights the need for novel drugs and their targets. Alkylation of purine bases can hinder DNA replication and if unresolved would eventually result in cell death. DNA-3-methyladenine glycosylase (MAG) is responsible for the repair of those alkylated bases. Plasmodium falciparum (Pf) MAG was characterized for its potential for development as an anti-malarial candidate.
METHODS
Native PfMAG from crude extract of chloroquine- and pyrimethamine-resistant P. falciparum K1 strain was partially purified using three chromatographic procedures. From bio-informatics analysis, primers were designed for amplification, insertion into pBAD202/D-TOPO and heterologous expression in Escherichia coli of recombinant PfMAG. Functional and biochemical properties of the recombinant enzyme were characterized.
RESULTS
PfMAG activity was most prominent in parasite schizont stages, with a specific activity of 147 U/mg (partially purified) protein. K1 PfMAG contained an insertion of AAT (coding for asparagine) compared to 3D7 strain and 16% similarity to the human enzyme. Recombinant PfMAG (74 kDa) was twice as large as the human enzyme, preferred double-stranded DNA substrate, and demonstrated glycosylase activity over a pH range of 4-9, optimal salt concentration of 100-200 mM NaCl but reduced activity at 250 mM NaCl, no requirement for divalent cations, which were inhibitory in a dose-dependent manner.
CONCLUSION
PfMAG activity increased with parasite development being highest in the schizont stages. K1 PfMAG contained an indel AAT (asparagine) not present in 3D7 strain and the recombinant enzyme was twice as large as the human enzyme. Recombinant PfMAG had a wide range of optimal pH activity, and was inhibited at high (250 mM) NaCl concentration as well as by divalent cations. The properties of PfMAG provide basic data that should be of assistance in developing anti-malarials against this potential parasite target.
Topics: DNA Glycosylases; Plasmodium falciparum; Protozoan Proteins
PubMed: 32762689
DOI: 10.1186/s12936-020-03355-w -
PLoS Pathogens Jun 2020New techniques for obtaining electron microscopy data through the cell volume are being increasingly utilized to answer cell biologic questions. Here, we present a...
New techniques for obtaining electron microscopy data through the cell volume are being increasingly utilized to answer cell biologic questions. Here, we present a three-dimensional atlas of Plasmodium falciparum ultrastructure throughout parasite cell division. Multiple wild type schizonts at different stages of segmentation, or budding, were imaged and rendered, and the 3D structure of their organelles and daughter cells are shown. Our high-resolution volume electron microscopy both confirms previously described features in 3D and adds new layers to our understanding of Plasmodium nuclear division. Interestingly, we demonstrate asynchrony of the final nuclear division, a process that had previously been reported as synchronous. Use of volume electron microscopy techniques for biological imaging is gaining prominence, and there is much we can learn from applying them to answer questions about Plasmodium cell biology. We provide this resource to encourage readers to consider adding these techniques to their cell biology toolbox.
Topics: Cytokinesis; Humans; Plasmodium falciparum
PubMed: 32511279
DOI: 10.1371/journal.ppat.1008587 -
Life Sciences Aug 2016Malaria is a life-threatening tropical disease, caused by the intracellular parasite Plasmodium falciparum. The World Health Organization counts malaria as one of the... (Review)
Review
Malaria is a life-threatening tropical disease, caused by the intracellular parasite Plasmodium falciparum. The World Health Organization counts malaria as one of the top ten causes of worldwide death. The unavailability of a successful malaria vaccine and the ever-increasing instances of drug resistance in the malaria parasite demand the discovery of new targets within P. falciparum for the development of next generation antimalarials. Fortunately, all apicomplexan parasites, including P. falciparum harbor a relict, non-photosynthetic plastid known as the apicoplast. The apicoplast is a semi-autonomous organelle within P. falciparum containing a 35kb circular genome. Despite a genome of its own, majority of the apicoplast proteins are encoded by the parasite nucleus and imported into the apicoplast. The organelle has been shown to be essential to P. falciparum survival and the loss the apicoplast manifests as a 'delayed death' response in the parasite. The apicoplast has evolved out of cyanobacteria in a complex, two step endosymbiotic event. As a result the architecture and the gene expression machinery of the apicoplast is quite bacteria-like and is susceptible to a wide range of antibiotics such as fosmidomycin, tetracycline, azithromycin, clindamycin and triclosan. The biosynthetic pathways for isoprenoids, fatty acids and heme operate within the malaria apicoplast, making the organelle an excellent target for drug development. The review focuses on the evolution, biology and the essentiality of the apicoplast within the malaria parasite and discusses some of the recent achievements towards the design and discovery of apicoplast targeted antimalarial compounds.
Topics: Animals; Antimalarials; Organelles; Plasmodium falciparum
PubMed: 27381078
DOI: 10.1016/j.lfs.2016.06.030