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https://www.readbyqxmd.com/read/29156781/toxoplasma-gondii-clp-family-protein-tgclpb1-plays-a-crucial-role-in-thermotolerance
#1
Shinuo Cao, Nali Du, Heming Chen, Yu Pang, Zhaoxia Zhang, Jun Zheng, Honglin Jia
Caseinolytic peptidase B (ClpB) plays a pivotal role in suppressing and reversing protein aggregation. Toxoplasma gondii is an intracellular parasitic protozoan that infects a wide variety of mammals and birds and therefore is exposed to a broad range of living condition. We screened ToxoDB (http://ToxoDB.org) and identified 10 putative T. gondii genes encoding members of the Clp superfamily of caseinolytic proteases and chaperones. Of these, we focused on characterizing the Class I ATP-dependent molecular chaperones TgClpB1, TgClpB2, and TgClpB3...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154995/a-map-of-the-subcellular-distribution-of-phosphoinositides-in-the-erythrocytic-cycle-of-the-malaria-parasite-plasmodium-falciparum
#2
Zeinab Ebrahimzadeh, Angana Mukherjee, Dave Richard
Despite representing a small percentage of the cellular lipids of eukaryotic cells, phosphoinositides (PIPs) are critical in various processes such as intracellular trafficking and signal transduction. Central to their various functions is the differential distribution of PIP species to specific membrane compartments through the actions of kinases, phosphatases and lipases. Despite their importance in the malaria parasite lifecycle, the subcellular distribution of most PIP species in this organism is still unknown...
November 15, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29141210/pfclpc-is-an-essential-clp-chaperone-required-for-plastid-integrity-and-clp-protease-stability-in-plasmodium-falciparum
#3
Anat Florentin, David W Cobb, Jillian D Fishburn, Michael J Cipriano, Paul S Kim, Manuel A Fierro, Boris Striepen, Vasant Muralidharan
The deadly malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid, known as the apicoplast, that functions to produce essential metabolites, and drugs that target the apicoplast are clinically effective. Several prokaryotic caseinolytic protease (Clp) genes have been identified in the Plasmodium genome. Using phylogenetic analysis, we focused on the Clp members that may form a regulated proteolytic complex in the apicoplast. We genetically targeted members of this complex and generated conditional mutants of the apicoplast-localized PfClpC chaperone and PfClpP protease...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29109165/validation-of-putative-apicoplast-targeting-drugs-using-a-chemical-supplementation-assay-in-cultured-human-malaria-parasites
#4
Taher Uddin, Geoffrey Ian McFadden, Christopher Dean Goodman
Malaria parasites contain a relict plastid, the apicoplast, which is considered an excellent drug target due to its bacterial-like ancestry. Numerous parasiticidals have been proposed to target the apicoplast, but few have had their actual targets substantiated. Isopentenyl pyrophosphate (IPP) production is the sole required function of the apicoplast in the blood stage of the parasite life cycle, and IPP supplementation rescues parasites from apicoplast perturbing drugs. Hence, any drug that kills parasites when IPP is supplied in culture must have a non-apicoplast target...
November 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29099876/archigregarines-of-the-english-channel-revisited-new-molecular-data-on-selenidium-species-including-early-described-and-new-species-and-the-uncertainties-of-phylogenetic-relationships
#5
Sonja Rueckert, Aleš Horák
BACKGROUND: Gregarines represent an important transition step from free-living predatory (colpodellids s.l.) and/or photosynthetic (Chromera and Vitrella) apicomplexan lineages to the most important pathogens, obligate intracellular parasites of humans and domestic animals such as coccidians and haemosporidians (Plasmodium, Toxoplasma, Eimeria, Babesia, etc.). While dozens of genomes of other apicomplexan groups are available, gregarines are barely entering the molecular age. Among the gregarines, archigregarines possess a unique mixture of ancestral (myzocytosis) and derived (lack of apicoplast, presence of subpellicular microtubules) features...
2017: PloS One
https://www.readbyqxmd.com/read/29096193/autophagy-in-apicomplexan-parasites
#6
REVIEW
Sébastien Besteiro
Autophagy is a highly conserved eukaryotic degradation process that permits the recycling of intracellular components. The molecular machinery and the functions of autophagy have been classically characterized in mammalian cells and yeast, but have long remained unexplored in less-studied eukaryotes. Apicomplexan parasites are early-diverging eukaryotes responsible for a number of important human and veterinary diseases. In light of recent investigations into autophagy function in two of these pathogens, Plasmodium and Toxoplasma, it seems their autophagy-related machinery could be involved in both a canonical degradative function, and a non-canonical role related to the apicoplast, a metabolically important organelle of endosymbiotic origin...
October 30, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29089429/autophagy-related-protein-atg18-regulates-apicoplast-biogenesis-in-apicomplexan-parasites
#7
Priyanka Bansal, Anuj Tripathi, Vandana Thakur, Asif Mohmmed, Pushkar Sharma
Mechanisms by which 3'-phosphorylated phosphoinositides (3'-PIPs) regulate the development of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are poorly understood. The catabolic process of autophagy, which is dependent on autophagy-related proteins (ATGs), is one of the major targets of 3'-PIPs in yeast and mammals. In the present study, we identified autophagy-related protein ATG18 as an effector of 3'-PIPs in these parasites. Pfalciparum ATG18 (PfATG18) and Tgondii ATG18 (TgATG18) interact with 3'-PIPs but exhibited differences in their specificity of interaction with the ligand PIP...
October 31, 2017: MBio
https://www.readbyqxmd.com/read/29072835/biological-studies-and-target-engagement-of-the-2-c-methyl-d-erythritol-4-phosphate-cytidylyltransferase-ispd-targeting-antimalarial-agent-1r-3s-mmv008138-and-analogs
#8
Maryam Ghavami, Emilio F Merino, Zhong-Ke Yao, Rubayet Elahi, Morgan E Simpson, Maria L Fernández-Murga, Joshua H Butler, Michael A Casasanta, Priscilla M Krai, Maxim M Totrov, Daniel J Slade, Paul R Carlier, Maria Belen Cassera
Malaria continues to be one of the deadliest diseases worldwide, and the emergence of drug resistance parasites is a constant threat. Plasmodium parasites utilize the methylerythritol phosphate (MEP) pathway to synthesize isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are essential for parasite growth. Previously, we and others identified that the Malaria Box compound MMV008138 targets the apicoplast and that parasite growth inhibition by this compound can be reversed by supplementation of IPP...
November 7, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28987288/relict-plastidic-metabolic-process-as-a-potential-therapeutic-target
#9
REVIEW
Drista Sharma, Rani Soni, Praveen Rai, Bhaskar Sharma, Tarun Kumar Bhatt
The alignment of the evolutionary history of parasites with that of plants provides a different panorama in the drug development process. The housing of different metabolic processes, essential for parasite survival, adds to the indispensability of the apicoplast. The different pathways responsible for fueling the apicoplast and parasite offer a myriad of proteins responsible for the apicoplast function. The studies emphasizing the target-based approaches might help in the discovery of antimalarials. The different putative drug targets and their roles are highlighted...
October 5, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28976181/exploring-the-untapped-biosynthetic-potential-of-apicomplexan-parasites
#10
Jack Ganley, Maria Toro-Moreno, Emily R Derbyshire
Apicomplexan parasites encompass a diverse group of eukaryotic intracellular pathogens that infect various animal hosts to cause disease. Intriguingly, apicomplexans possess a unique organelle of algal origin, the apicoplast, which phylogenetically links these parasites to dinoflagellates and photosynthetic, coral-associated organisms. While production of secondary metabolites in closely-related organisms has been thoroughly examined, it remains widely unexplored in apicomplexans. In this perspective, we discuss previous work toward understanding secondary metabolite building block biosynthesis in apicomplexans and highlight the unexplored enzymology and biosynthetic potential of these parasites in the context of evolution...
October 4, 2017: Biochemistry
https://www.readbyqxmd.com/read/28974215/species-and-genotype-diversity-of-plasmodium-in-malaria-patients-from-gabon-analysed-by-next-generation-sequencing
#11
Albert Lalremruata, Sankarganesh Jeyaraj, Thomas Engleitner, Fanny Joanny, Annika Lang, Sabine Bélard, Ghyslain Mombo-Ngoma, Michael Ramharter, Peter G Kremsner, Benjamin Mordmüller, Jana Held
BACKGROUND: Six Plasmodium species are known to naturally infect humans. Mixed species infections occur regularly but morphological discrimination by microscopy is difficult and multiplicity of infection (MOI) can only be evaluated by molecular methods. This study investigated the complexity of Plasmodium infections in patients treated for microscopically detected non-falciparum or mixed species malaria in Gabon. METHODS: Ultra-deep sequencing of nucleus (18S rRNA), mitochondrion, and apicoplast encoded genes was used to evaluate Plasmodium species diversity and MOI in 46 symptomatic Gabonese patients with microscopically diagnosed non-falciparum or mixed species malaria...
October 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28931453/molecular-characterization-and-distribution-of-plasmodium-matutinum-a-common-avian-malaria-parasite
#12
Gediminas Valkiūnas, Mikas Ilgūnas, Dovilė Bukauskaitė, Vaidas Palinauskas, Rasa Bernotienė, Tatjana A Iezhova
Species of Plasmodium (Plasmodiidae, Haemosporida) are widespread and cause malaria, which can be severe in avian hosts. Molecular markers are essential to detect and identify parasites, but still absent for many avian malaria and related haemosporidian species. Here, we provide first molecular characterization of Plasmodium matutinum, a common agent of avian malaria. This parasite was isolated from a naturally infected thrush nightingale Luscinia luscinia (Muscicapidae). Fragments of mitochondrial, apicoplast and nuclear genomes were obtained...
November 2017: Parasitology
https://www.readbyqxmd.com/read/28917450/a-novel-class-of-plasmodial-clpp-protease-inhibitors-as-potential-antimalarial-agents
#13
Sourabh Mundra, Vandana Thakur, Angelica M Bello, Sumit Rathore, Mohd Asad, Lianhu Wei, Jane Yang, Sai Kumar Chakka, Radhakrishnan Mahesh, Pawan Malhotra, Asif Mohmmed, Lakshmi P Kotra
The prokaryotic ATP-dependent ClpP protease, localized in the relict plastid of malaria parasite, represents a potential drug target. In the present study, we utilized in silico structure-based screening and medicinal chemistry approaches to identify a novel pyrimidine series of compounds inhibiting P. falciparum ClpP protease activity and evaluated their antiparasitic activities. Structure-activity relationship indicated that morpholine moiety at C2, an aromatic substitution at N3 and a 4-oxo moiety on the pyrimidine are important for potent inhibition of ClpP enzyme along with antiparasiticidal activity...
September 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28902970/a-genetic-screen-in-rodent-malaria-parasites-identifies-five-new-apicoplast-putative-membrane-transporters-one-of-which-is-essential-in-human-malaria-parasites
#14
Claire P Sayers, Vanessa Mollard, Hayley D Buchanan, Geoffrey I McFadden, Christopher D Goodman
The malaria-causing parasite, Plasmodium, contains a unique non-photosynthetic plastid known as the apicoplast. The apicoplast is an essential organelle bound by four membranes. Although membrane transporters are attractive drug targets, only two transporters have been characterised in the malaria parasite apicoplast membranes. We selected 27 candidate apicoplast membrane proteins, 20 of which are annotated as putative membrane transporters, and performed a genetic screen in P. berghei to determine blood stage essentiality and subcellular localisation...
September 13, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28842355/first-genetic-characterization-of-toxoplasma-gondii-infection-in-poultry-meat-intended-for-human-consumption-in-eastern-china
#15
Yang Zou, Lan-Bi Nie, Nian-Zhang Zhang, Feng-Cai Zou, Xing-Quan Zhu, Wei Cong
Toxoplasma gondii can infect nearly all warm-blooded animals including birds. However, limited information on the molecular epidemiology and genotypes of T. gondii infecting poultry is available in China. Therefore, the present study characterized T. gondii genotypes in poultry meat in eastern China. During August 2015 and September 2016, muscle tissue samples collecting from 414 poultries (257 chickens, 115 ducks and 42 geese) in Shandong provinces were used to detect the T. gondii B1 gene by a semi-nested PCR, and the positive samples were genotyped at 10 nuclear loci (i...
August 24, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28826494/small-molecule-inhibition-of-apicomplexan-ftsh1-disrupts-plastid-biogenesis-in-human-pathogens
#16
Katherine Amberg-Johnson, Sanjay B Hari, Suresh M Ganesan, Hernan A Lorenzi, Robert T Sauer, Jacquin C Niles, Ellen Yeh
The malaria parasite Plasmodium falciparum and related apicomplexan pathogens contain an essential plastid organelle, the apicoplast, which is a key anti-parasitic target. Derived from secondary endosymbiosis, the apicoplast depends on novel, but largely cryptic, mechanisms for protein/lipid import and organelle inheritance during parasite replication. These critical biogenesis pathways present untapped opportunities to discover new parasite-specific drug targets. We used an innovative screen to identify actinonin as having a novel mechanism-of-action inhibiting apicoplast biogenesis...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28810863/multiple-essential-functions-of-plasmodium-falciparum-actin-1-during-malaria-blood-stage-development
#17
Sujaan Das, Leandro Lemgruber, Chwen L Tay, Jake Baum, Markus Meissner
BACKGROUND: The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated...
August 15, 2017: BMC Biology
https://www.readbyqxmd.com/read/28769894/a-historical-overview-of-research-on-babesia-orientalis-a-protozoan-parasite-infecting-water-buffalo
#18
REVIEW
Lan He, Qin Liu, Baoan Yao, Yanqin Zhou, Min Hu, Rui Fang, Junlong Zhao
Babesiosis is a globally important zoonotic disease caused by tick-borne intraerythrocytic protozoan of the genus Babesia (phylum apicomplexa). In China, there are five species that infect cattle buffalo and cause great economic loss, which include Babesia bigemina, B. bovis, B. major, B. ovata, and B. orientalis. Among them, B. orientalis is the most recently identified new Babesia species epidemic in China. This review summarized the work done in the past 33 years to give an overview of what learned about this parasite...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28750796/the-n-terminal-extension-of-the-p-falciparum-gbp130-signal-peptide-is-irrelevant-for-signal-sequence-function
#19
Corinna Meyer, Luis Barniol, Jan A Hiss, Jude M Przyborski
The malaria parasite P. falciparum exports a large number of proteins to its host cell, the mature human erythrocyte. Although the function of the majority of these proteins is not well understood, many exported proteins appear to play a role in modification of the erythrocyte following invasion. Protein export to the erythrocyte is a secretory process that begins with entry to the endoplasmic reticulum. For most exported proteins, this step is mediated by hydrophobic signal peptides found towards the N-terminal end of proteins...
July 17, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28695709/-fe-s-cluster-assembly-in-the-apicoplast-and-its-indispensability-in-mosquito-stages-of-the-malaria-parasite
#20
Manish Charan, Hadi Hasan Choudhary, Nidhi Singh, Mohammad Sadik, Mohammad Imran Siddiqi, Satish Mishra, Saman Habib
The relict plastid (apicoplast) of the malaria parasite is the site for important biochemical pathways and is essential for parasite survival. The sulfur mobilization (SUF) pathway of iron-sulfur [Fe-S] cluster assembly in the apicoplast of Plasmodium spp. is of interest due to its absence in the human host suggesting the possibility of antimalarial intervention through apicoplast [Fe-S] biogenesis. We report biochemical characterization of components of the Plasmodium falciparum apicoplast SUF pathway after the first step of SUF...
August 2017: FEBS Journal
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