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https://www.readbyqxmd.com/read/28423214/plasmodium-falciparum-otu-like-cysteine-protease-pfotu-is-essential-for-apicoplast-homeostasis-and-associates-with-non-canonical-role-of-atg8
#1
Gaurav Datta, Mohammad E Hossain, Mohd Asad, Sumit Rathore, Asif Mohmmed
The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, two parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel OTU domain containing cysteine protease of Plasmodium falciparum (PfOTU). A C-terminal regulatable fluorescent affinity (RFA) tag on native protein was utilized for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU, and its association with the apicoplast...
April 18, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28419631/tgpl2-a-patatin-like-phospholipase-domain-containing-protein-is-involved-in-the-maintenance-of-apicoplast-lipids-homeostasis-in-toxoplasma
#2
Maude F Lévêque, Laurence Berry, Yoshiki Yamaryo-Botté, Hoa Mai Nguyen, Marine Galera, Cyrille Y Botté, Sébastien Besteiro
Patatin-like phospholipases are involved in numerous cellular functions, including lipid metabolism and membranes remodeling. The patatin-like catalytic domain, whose phospholipase activity relies on a serine-aspartate dyad and an anion binding box, is widely spread among prokaryotes and eukaryotes. We describe TgPL2, a novel patatin-like phospholipase domain-containing protein from the parasitic protist Toxoplasma gondii. TgPL2 is a large protein, in which the key motifs for enzymatic activity are conserved in the patatin-like domain...
April 17, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28361906/herbicidal-properties-of-antimalarial-drugs
#3
Maxime G Corral, Julie Leroux, Keith A Stubbs, Joshua S Mylne
The evolutionary relationship between plants and the malarial parasite Plasmodium falciparum is well established and underscored by the P. falciparum apicoplast, an essential chloroplast-like organelle. As a result of this relationship, studies have demonstrated that herbicides active against plants are also active against P. falciparum and thus could act as antimalarial drug leads. Here we show the converse is also true; many antimalarial compounds developed for human use are highly herbicidal. We found that human antimalarial drugs (e...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344153/plant-hormone-cytokinins-control-cell-cycle-progression-and-plastid-replication-in-apicomplexan-parasites
#4
Syed Bilal Ahmad Andrabi, Michiru Tahara, Ryuma Matsubara, Tomoko Toyama, Hiroka Aonuma, Hitoshi Sakakibara, Makoto Suematsu, Kazuyuki Tanabe, Tomoyoshi Nozaki, Kisaburo Nagamune
Cytokinins are plant hormones that are involved in regulation of cell proliferation, cell cycle progression, and cell and plastid development. Here, we show that the apicomplexan parasites Toxoplasma gondii and Plasmodium berghei, an opportunistic human pathogen and a rodent malaria agent, respectively, produce cytokinins via a biosynthetic pathway similar to that in plants. Cytokinins regulate the growth and cell cycle progression of T. gondii by mediating expression of the cyclin gene TgCYC4. A natural form of cytokinin, trans-zeatin (t-zeatin), upregulated expression of this cyclin, while a synthetic cytokinin, thidiazuron, downregulated its expression...
March 23, 2017: Parasitology International
https://www.readbyqxmd.com/read/28314772/two-phylogenetically-and-compartmentally-distinct-cdp-diacylglycerol-synthases-cooperate-for-lipid-biogenesis-in-toxoplasma-gondii
#5
Pengfei Kong, Christoph-Martin Ufermann, Diana Lm Zimmermann, Qing Yin, Xun Suo, J Bernd Helms, Jos F Brouwers, Nishith Gupta
Toxoplasma gondii is among the most prevalent protozoan parasites, which infects a wide range of organisms including one-third of the human population. Its rapid intracellular replication within a vacuole requires efficient synthesis of glycerophospholipids. Cytidine diphosphate-diacylglycerol (CDP-DAG) serves as a major precursor for phospholipid synthesis. Given the peculiarities of lipid biogenesis, understanding the mechanism and physiological importance of CDP-DAG synthesis is particularly relevant in T...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28260517/capi-computational-model-for-apicoplast-inhibitors-prediction-against-plasmodium-parasite
#6
Surabhi Dixit, Deepak Singla
Background Discovery of apicoplast as a drug target offers a new direction in the development of novel anti-malarial compounds, especially against the drug-resistant strains. Drugs such as azithromycin were reported to block the apicoplast development that leads to unusual phenotypes affecting the parasite. This phenomenon suggeststhat identification of new apicoplast inhibitors will aid in the anti-malarial drug discovery. Therefore, in this study, we developed a computational model to predict apicoplast inhibitors by applying state-of-the-art machine learning techniques...
March 1, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28251546/plasmodium-falciparum-apicoplast-and-its-transcriptional-regulation-through-calcium-signaling
#7
REVIEW
Praveen Rai, Drista Sharma, Rani Soni, Nazia Khatoon, Bhaskar Sharma, Tarun Kumar Bhatt
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...
April 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/28163699/a-systematic-review-of-in-vitro-and-in-vivo-activities-of-anti-toxoplasma-drugs-and-compounds-2006-2016
#8
REVIEW
Mahbobeh Montazeri, Mehdi Sharif, Shahabeddin Sarvi, Saeed Mehrzadi, Ehsan Ahmadpour, Ahmad Daryani
The currently available anti-Toxoplasma agents have serious limitations. This systematic review was performed to evaluate drugs and new compounds used for the treatment of toxoplasmosis. Data was systematically collected from published papers on the efficacy of drugs/compounds used against Toxoplasma gondii (T. gondii) globally during 2006-2016. The searched databases were PubMed, Google Scholar, Science Direct, ISI Web of Science, EBSCO, and Scopus. One hundred and eighteen papers were eligible for inclusion in this systematic review, which were both in vitro and in vivo studies...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28100223/surface-attachment-promoted-by-the-actomyosin-system-of-toxoplasma-gondii-is-important-for-efficient-gliding-motility-and-invasion
#9
Jamie A Whitelaw, Fernanda Latorre-Barragan, Simon Gras, Gurman S Pall, Jacqueline M Leung, Aoife Heaslip, Saskia Egarter, Nicole Andenmatten, Shane R Nelson, David M Warshaw, Gary E Ward, Markus Meissner
BACKGROUND: Apicomplexan parasites employ a unique form of movement, termed gliding motility, in order to invade the host cell. This movement depends on the parasite's actomyosin system, which is thought to generate the force during gliding. However, recent evidence questions the exact molecular role of this system, since mutants for core components of the gliding machinery, such as parasite actin or subunits of the MyoA-motor complex (the glideosome), remain motile and invasive, albeit at significantly reduced efficiencies...
January 18, 2017: BMC Biology
https://www.readbyqxmd.com/read/28068997/absence-of-in-vivo-selection-for-k13-mutations-after-artemether-lumefantrine-treatment-in-uganda
#10
Betty Balikagala, Toshihiro Mita, Mie Ikeda, Miki Sakurai, Shouki Yatsushiro, Nobuyuki Takahashi, Shin-Ichiro Tachibana, Mary Auma, Edward H Ntege, Daisuke Ito, Eizo Takashima, Nirianne Marie Q Palacpac, Thomas G Egwang, Joseph Okello Onen, Masatoshi Kataoka, Eisaku Kimura, Toshihiro Horii, Takafumi Tsuboi
BACKGROUND: Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein...
January 9, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28062360/determination-of-glutathione-redox-potential-and-ph-value-in-subcellular-compartments-of-malaria-parasites
#11
Franziska Mohring, Mahsa Rahbari, Bernd Zechmann, Stefan Rahlfs, Jude M Przyborski, Andreas J Meyer, Katja Becker
The malaria parasite Plasmodium falciparum is exposed to multiple sources of oxidative challenge during its complex life cycle in the Anopheles vector and its human host. In order to further elucidate redox-based parasite host cell interactions and mechanisms of drug action, we targeted the genetically encoded glutathione redox sensor roGFP2 coupled to human glutaredoxin 1 (roGFP2-hGrx1) as well as the ratiometric pH sensor pHluorin to the apicoplast and the mitochondrion of P. falciparum. Using live cell imaging, this allowed for the first time the determination of the pH values of the apicoplast (7...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28026138/towards-a-molecular-architecture-of-the-centrosome-in-toxoplasma-gondii
#12
REVIEW
Juliette Morlon-Guyot, Maria E Francia, Jean-François Dubremetz, Wassim Daher
Toxoplasma gondii is the causative agent of toxoplasmosis. The pathogenicity of this unicellular parasite is tightly linked to its ability to efficiently proliferate within its host. Tachyzoites, the fast dividing form of the parasite, divide by endodyogeny. This process involves a single round of DNA replication, closed nuclear mitosis, and assembly of two daughter cells within a mother. The successful completion of endodyogeny relies on the temporal and spatial coordination of a plethora of simultaneous events...
February 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28007455/characterization-of-4-hydroxy-3-methylbut-2-en-1-yl-diphosphate-synthase-ispg-from-plasmodium-vivax-and-it-s-potential-as-an-antimalarial-drug-target
#13
Gagandeep Singh Saggu, Shilpi Garg, Zarna Rajeshkumar Pala, Sushil Kumar Yadav, Sanjay Kumar Kochar, Dhanpat Kumar Kochar, Vishal Saxena
The prokaryotic type Methyl Erythritol phosphate (MEP) pathway functional in the apicoplast of Plasmodium is indispensable for the erythrocytic stages of the parasite. It is the sole process of isoprenoids biosynthesis in the parasite and is different from that in humans. Among the seven enzymes known to be functional in the MEP pathway in prokaryotes, most enzymes from Plasmodium are yet uncharacterized. The penultimate enzyme of this pathway 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase (IspG), has been shown to act as a key target molecule in prokaryotes, where its deletion results in impairment of many housekeeping functions...
December 20, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27916258/the-apicoplast-genomes-of-two-taxonomic-units-of-babesia-from-sheep
#14
Tao Wang, Guiquan Guan, Pasi K Korhonen, Anson V Koehler, Ross S Hall, Neil D Young, Hong Yin, Robin B Gasser
The apicoplast (ap) is a unique, non-photosynthetic organelle found in most apicomplexan parasites. Due to the essential roles that this organelle has, it has been widely considered as target for drugs against diseases caused by apicomplexans. Exploring the ap genomes of such parasites would provide a better understanding of their systematics and their basic molecular biology for therapeutics. However, there is limited information available on the ap genomes of apicomplexan parasites. In the present study, the ap genomes of two operational taxonomic units of Babesia (known as Babesia sp...
January 15, 2017: Veterinary Parasitology
https://www.readbyqxmd.com/read/27899155/comparative-sequence-analysis-of-cyclospora-cayetanensis-apicoplast-genomes-originating-from-diverse-geographical-regions
#15
Hediye Nese Cinar, Yvonne Qvarnstrom, Yuping Wei-Pridgeon, Wen Li, Fernanda S Nascimento, Michael J Arrowood, Helen R Murphy, AhYoung Jang, Eunje Kim, RaeYoung Kim, Alexandre da Silva, Gopal R Gopinath
BACKGROUND: Cyclospora cayetanensis is an emerging coccidian parasite that causes endemic and epidemic diarrheal disease called cyclosporiasis, and this infection is associated with consumption of contaminated produce or water in developed and developing regions. Food-borne outbreaks of cyclosporiasis have occurred almost every year in the USA since the 1990s. Investigations of these outbreaks are currently hampered due to lack of molecular epidemiological tools for trace back analysis...
November 29, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27821055/babesia-microti-from-humans-and-ticks-hold-a-genomic-signature-of-strong-population-structure-in-the-united-states
#16
Giovanna Carpi, Katharine S Walter, Choukri Ben Mamoun, Peter J Krause, Andrew Kitchen, Timothy J Lepore, Ankit Dwivedi, Emmanuel Cornillot, Adalgisa Caccone, Maria A Diuk-Wasser
BACKGROUND: Babesia microti is an emerging tick-borne apicomplexan parasite with increasing geographic range and incidence in the United States. The rapid expansion of B. microti into its current distribution in the northeastern USA has been due to the range expansion of the tick vector, Ixodes scapularis, upon which the causative agent is dependent for transmission to humans. RESULTS: To reconstruct the history of B. microti in the continental USA and clarify the evolutionary origin of human strains, we used multiplexed hybrid capture of 25 B...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27793563/targeting-protein-translation-in-organelles-of-the-apicomplexa
#17
REVIEW
Christopher D Goodman, Charisse Flerida A Pasaje, Kit Kennedy, Geoffrey I McFadden, Stuart A Ralph
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...
October 25, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/27773518/the-apicoplast-now-you-see-it-now-you-don-t
#18
REVIEW
Geoffrey Ian McFadden, Ellen Yeh
Parasites such as Plasmodium and Toxoplasma possess a vestigial plastid homologous to the chloroplasts of algae and plants. The plastid (known as the apicoplast; for apicomplexan plastid) is non-photosynthetic and very much reduced, but has clear endosymbiotic ancestry including a circular genome that encodes RNAs and proteins and a suite of bacterial biosynthetic pathways. Here we review the initial discovery of the apicoplast, and recount the major new insights into apicoplast origin, biogenesis and function...
February 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/27719626/metabolic-inhibitors-as-antiparasitic-drugs-pharmacological-biochemical-and-molecular-perspectives
#19
REVIEW
Suprabhat Mukherjee, Niladri Mukherjee, Prajna Gayen, Priya Roy, Santi P Sinha Babu
BACKGROUND: Human diseases caused by the infectious parasites have been one of the major problems throughout the evolutionary journey. Protozoan and metazoan parasitic infections result in a large number of deaths, disabilities and socio-economic loss worldwide to date. Despite the best efforts for developing suitable antiparasitics, these infections take a massive toll on human health. The prevalence of emerging resistance to the existing drugs, lack of efficacy and toxic side effects are as added complications...
2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27679614/new-insight-into-isoprenoids-biosynthesis-process-and-future-prospects-for-drug-designing-in-plasmodium
#20
REVIEW
Gagandeep S Saggu, Zarna R Pala, Shilpi Garg, Vishal Saxena
The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures...
2016: Frontiers in Microbiology
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