Download or read book Characterisation of Trafficking Signals Shared by Different Types of Exported Proteins in the Human Malaria Parasite Plasmodium Falciparum written by Ann-Katrin Ullrich and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterisation of the Plasmodium Falciparum Export Complex written by Brendan Elsworth and published by . This book was released on 2015 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium parasites extensively remodel the mammalian host cells they infect, namely the erythrocytes and hepatocytes. This is achieved through exporting hundreds of parasite proteins into the host where they play many virulence related roles including altering membrane permeability to acquire nutrients for rapid growth and for increasing immune evasion. Proteins are secreted from the parasite into the vacuole that surrounds them, where they must then pass across the parasitophorous vacuole membrane (PVM) to gain access to the host cytoplasm. It has previously been shown that a protein complex, the Plasmodium Translocon of EXported proteins (PTEX), is found on the PVM and is most likely the protein translocon responsible for this export process. To validate and further dissect PTEX function, a conditional expression system that utilizes the glmS riboswitch was employed to conditionally knockdown the levels of PTEX150 within parasites. Using this approach, even a relatively low level of PTEX150 knockdown lead to a significant decrease in the ability of the parasites to export proteins across the PVM. This failure of protein export across the PVM arrested growth and eventually caused parasite death. Interestingly, the export of all classes of protein cargoes tested, including PfEMP1, were blocked upon PTEX150 knockdown suggesting PTEX may serve as a single portal for export. This demonstrates the importance of PTEX to the malaria parasite and validates it as a potent drug target, since blocking it would prevent hundreds of exported proteins from reaching their functional destinations. To further investigate the specific function of PTEX150 we performed C-terminal truncations in order to generate a parasite line with a partially defective protein. These lines showed destabilisation of the PTEX complex, suggesting that the C-terminus of PTEX150, while not essential for PTEX function or the absolute binding of the other components, is required for stabilising the PTEX complex. Interestingly, these parasites did not show a defect in either their ability to grow or export proteins. To further investigate the effect of PTEX150 knockdown on parasite health the new permeability pathways (NPPs) were investigated. To do this a novel method was developed to investigate NPP function using luciferase. This method is highly sensitive, reducing the amount of parasites required as well as removing the need to purify parasites from culture. The effect of PTEX150 knockdown on NPPs was unclear using this method. Due to the high sensitivity and ease of this method it was developed as a HTS to discover NPP inhibitors. Using this method the malaria box of 400 compounds was screened. Importantly, two compounds, MMV020439and MMV007571, showed inhibitory activity significantly higher than the control compound NPPB.
Download or read book Characterization of the Protein Export Steps at the Parasite host Cell Interface of the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Paolo Mesén-Ramírez and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization and Visualization of Protein Export in the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Christof Grüring and published by . This book was released on 2011 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Characterization of the Protein Export Steps at the Parasite host Cell Interface of the Human Malaria Parasite Plasmodium Falciparum Welch 1897 written by Paolo Mesén-Ramírez and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Trafficking and Biochemical Characterization of Plasmodium Falciparum Maurer s Cleft Two Transmembrane Protein written by Raghavendra Yadavalli and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum virulence proteins and molecules required for assembly of the knobs used for cytoadherence are exported through the Maurer's clefts which are formed in the erythrocyte cytoplasm immediately following merozoite invasion into the erythrocyte host cell. Proteins participating in knob formation, cytoadherence or immune evasion include variant-surface antigens (VSAs) that are trafficked alone or chaperoned by other parasite proteins through the Maurer's clefts. In this study, recombinant PfMC-2TM was expressed using HeLa based in vitro human cell free expression system. Further, the stage specific expression, trafficking, solubility and topology of endogenous PfMC-2TM in the parasite and erythrocyte cytoplasm was investigated in 3D7 and FC-27 strains of P. falciparum. Detailed cell biological and biochemical characterizations were performed to identify the mode of PfMC-2TM export from the parasite to erythrocyte cytoplasm. Following Brefeldin A (BFA) treatment of parasites, PfMC-2TM traffic was evaluated using immunofluorescence and western blotting with antibodies reactive with PfMC-2TM. Our data shows that PfMC-2TM is sensitive to BFA treatment in the ring and trophozoite stage. Permeabilization of infected erythrocytes with streptolysin O (SLO) and saponin, showed that the N and C-termini of PfMC-2TM are exposed to the erythrocyte cytoplasm with the central portion of the protein protected in the MC membranes. PfMC-2TM was expressed as early as 4 h post invasion (hpi), was tightly colocalized with Maurer's cleft resident protein REX-1 and trafficked to the erythrocyte membrane without a change in solubility. PfMC-2TM associates with the infected erythrocyte membrane as an integral membrane protein and is seen to be transiently exposed on the infected red blood cell surface. PfMC-2TM remains insoluble upon association with the MC and erythrocyte membrane, suggestive of protein-lipid interactions with membranes of the MC and erythrocyte. PfMC-2TM is an additional marker of the nascent MCs, that can be used as a clinical marker of early blood stage infection.
Download or read book Tentative Isolation of a Novel Organelle Predicted to be Involved in Trafficking of PfEMP1 in Plasmodium Falciparum written by Abhishek Awasthi and published by . This book was released on 2009 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: The most virulent human malaria parasite, Plasmodium falciparum, remodels the red blood cell (RBC) during its intra-erythrocytic stage and exports proteins to the RBC cytoplasm and membrane. The parasite-encoded antigenic variant protein, Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1), gets exported and presented on knobs to mediate cytoadherence to the endothelial cells. The PfEMP1 export to the RBC surface is mediated by the parasite-induced membranous trafficking machinery. The ultra-structure of this trafficking system and its components is only partly defined. Recently a population of spherical vesicles with a diameter of ~80 nm has been reported to exhibit PfEMP1 labeling, which suggests that these vesicles could potentially be involved in the delivery of internal membrane protein cargo to the RBC membrane.
Download or read book Molecular Cloning and Characterization of Genes Encoding Putative Signal Transduction Proteins from the Human Malaria Parasite Plasmodium Falciparum written by Jiliang Li and published by . This book was released on 1997 with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Vesicle Targeting in Plasmodium Falciparum written by Lawrence Sumanjah Ayong and published by . This book was released on 2009 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins of the SNARE (Soluble N-ethylmaleimide sensitive factor attachment protein receptor) super-family have been characterized as playing an essential role in vesicle targeting and fusion in all eukaryotes. The intracellular malaria parasite Plasmodium falciparum exhibits an unusual endomembrane system that is characterized by an unstacked Golgi apparatus, a developmentally induced apical complex, and various organellar structures of parasite origin in the infected host cells. How malaria parasites target nuclear-encoded proteins to these novel compartments is a central question in Plasmodium cell biology. Ultrastructural studies elsewhere have implicated the participation of specialized vesicular elements in transport of virulence proteins, including various cytoadherance and host cell remodeling factors, into the infected erythrocyte cytoplasm. However, little is known about the machineries that define the directionality of vesicle trafficking in malaria parasites. We hypothesized that the P. falciparum SNARE proteins would exhibit novel features required for vesicle targeting to the parasite-specific compartments. We then identified for the first time and confirmed the expression of eighteen SNARE genes in P. falciparum. Members of the PfSNAREs exhibit atypical structural features (Ayong et al., 2007, Molecular & Biochemical Parasitology, 152(2), 113-122). Among the atypical PfSNAREs, PfSec22 contains an unusual insertion of the Plasmodium export element (PEXEL) within its profilin-like longin domain, preceded by an N-terminal hydrophobic segment.
Download or read book World Malaria Report 2019 written by World Health Organization and published by . This book was released on 2019-08-28 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2019 provides a comprehensive update on global and regional malaria data and trends. The report tracks investments in malaria programs and research as well as progress across all intervention areas: prevention, diagnosis, treatment, elimination, and surveillance. It also includes dedicated chapters on the consequences of malaria on maternal infant and child health the "High Burden to High Impact" approach as well as biological threats to the fight against malaria. The 2019 report is based on information received from more than 80 countries and areas with ongoing malaria transmission. This information is supplemented by data from national household surveys and databases held by other organizations.
Download or read book The Malaria Genome Projects written by Irwin W. Sherman and published by World Scientific. This book was released on 2012 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: The year 2012 marks the tenth anniversary of the announcement of the genome sequence of the human malaria parasite Plasmodium falciparum and that of its mosquito vector Anopheles. The genome sequences were a result of the Plasmodium falciparum Genome Project. This book covers in detail the biology of malaria parasites and the mosquitoes that transmit the disease, how the Genome Project came into being, the people who created it, and the cadre of scientists who are attempting to see the promise of the Project realized. The promise was: a more complete understanding of the genes of the parasite (and its vector) would provide a rational basis for the development of antimalarial drugs and vaccines, allow a better understanding of the regulation of the complex life cycle in the red blood and liver cells of the human, identify the genes the parasite uses to thwart the host immune response and the ways in which the parasite evades cure by drug treatments, as well as leading to more effective measures of control transmission. The hope was that cracking the genetic code of Plasmodium and Anopheles would reveal the biochemical Achilles heel of the parasite and its vector, leading to the development of novel drugs and better methods of control, and by finding the targets of protective immunity could result in the manufacture of effective vaccines. Through a historic approach, this book will allow for those new to the field, or those with insufficient background in the sciences, to have an easier entry point. Even scientists already working in the field may better appreciate how discoveries made in the past can impact the direction of future research.
Download or read book World Malaria Report 2015 written by World Health Organization and published by World Health Organization. This book was released on 2016-01-30 with total page 283 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2015assesses global malaria disease trends and changes in the coverage and financing of malaria control programs between 2000 and 2015. It also summarizes progress towards international targets, and provides regional and country profiles that summarize trends in each WHO region and each country with malaria. The report is produced with the help of WHO regional and country offices, ministries of health in endemic countries, and a broad range of other partners. The data presented are assembled from the 96 countries and territories with ongoing malaria transmission, and a further five countries that have recently eliminated malaria. Most data are those reported for 2014 and 2015, although in some cases projections have been made into 2015, to assess progress towards targets for 2015.
Download or read book Natural Remedies in the Fight Against Parasites written by Hanem Khater and published by BoD – Books on Demand. This book was released on 2017-07-12 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book emphasizes past and current research efforts about principles of natural control of major parasites affecting humans, animals, and crops. Each chapter is a complete and integrated subject that presents a problem and confers on the safe alternatives to chemicals. This book discusses and updates information about three major topics of natural remedies. The first topic is represented in a chapter outlining important information on biological control of parasites, the second topic is represented in three chapters dealing with botanicals as promising antiparasitic agents, and the last four chapters deal with miscellaneous control strategies against parasites. This easily readable book is designed precisely for students as well as professors linked with the field of parasitic control. We enhanced words with breathing areas in the form of graphical abstracts, figures, photographs, and tables.
Download or read book Malaria Methods and Protocols written by Denise L. Doolan and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 606 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Plasmodium spp. parasite was identified as the causative agent of malaria in 1880, and the mosquito was identified as the vector in 1897. Despite subsequent efforts focused on the epidemiology, cell biology, immunology, molecular biology, and clinical manifestations of malaria and the Plasmodium parasite, there is still no licensed vaccine for the prevention of malaria. Physical barriers (bed nets, window screens) and chemical prevention methods (insecticides and mosquito repellents) intended to interfere with the transmission of the disease are not highly effective, and the profile of resistance of the parasite to chemoprophylactic and chemotherapeutic agents is increasing. The dawn of the new millennium has seen a resurgence of interest in the disease by government and philanthropic organizations, but we are still faced with compl- ities of the parasite, the host, and the vector, and the interactions among them. Malaria Methods and Protocols offers a comprehensive collection of protocols describing conventional and state-of-the-art techniques for the study of malaria, as well as associated theory and potential problems, written by experts in the field. The major themes reflected here include assessing the risk of infection and severity of disease, laboratory models, diagnosis and typing, molecular biology techniques, immunological techniques, cell biology techniques, and field applications.
Download or read book Red Cell Membranes written by Stephen Byron Shohet and published by . This book was released on 1988 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Apicomplexan Parasites written by Katja Becker and published by John Wiley & Sons. This book was released on 2011-01-19 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This handbook is the first dealing with the discovery of drugs directed against apicomplexan parasites. Amongst others, this group of endoparasites includes the causative agents of Malaria, Toxoplasmosis, and Babesiosis, the latter occurring mainly in animals. Written by renowned scientific experts from academia and industry, the book focuses on currentdrug development approaches for all apicomplexan diseases making it appealing to a large audience, ranging from research labs in academia to the human and veterinarian pharmaceutical industry. This work is the second volume of the new book series 'Drug Discovery in Infectious Diseases', edited by Prof. Dr Paul M. Selzer.
Download or read book Flexible Viruses written by Vladimir Uversky and published by John Wiley & Sons. This book was released on 2012-02-07 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides up-to-date information on experimental and computational characterization of the structural and functional properties of viral proteins, which are widely involved in regulatory and signaling processes. With chapters by leading research groups, it features current information on the structural and functional roles of intrinsic disorders in viral proteomes. It systematically addresses the measles, HIV, influenza, potato virus, forest virus, bovine virus, hepatitis, and rotavirus as well as viral genomics. After analyzing the unique features of each class of viral proteins, future directions for research and disease management are presented.
