Download or read book Molecular Mechanisms of Plasmodium Red Blood Cell Invasion written by Brian Michael Malpede and published by . This book was released on 2015 with total page 147 pages. Available in PDF, EPUB and Kindle. Book excerpt: The malaria parasite Plasmodium utilizes specialized proteins for adherence to cellular receptors in its mosquito vector and human host. Adherence is critical for parasite development, host cell traversal and invasion, and protection from vector and host immune mechanisms. These vital roles have identified several adhesins as vaccine candidates. A deficiency in current adhesin-based vaccines is induction of antibodies targeting non-conserved, non-functional, and decoy epitopes due to the use of full length proteins or binding domains. To alleviate the elicitation of non-inhibitory antibodies, conserved functional regions of proteins must be identified and exploited. Structural biology provides the tools necessary to achieve this goal, and has succeeded in defining biologically functional receptor binding and oligomerization interfaces for a number of promising malaria vaccine candidates. A critical step in the Plasmodium life cycle is adhesion to and invasion of erythrocytes by the merozoite during blood stage growth. The invasion process requires the formation of a tight junction between parasite adhesive proteins and red cell receptors. Formation of this junction allows the merozoite to engage and enter the red cell to form the parasitophorous vacuole. The Erythrocyte-binding-like (EBL) family of cellular adhesion proteins is implicated in the formation of this essential tight junction. Receptor binding by the EBL family of invasion ligands has been localized to a specific portion of each EBL protein designated Region II (RII). This region is composed of the Duffy- binding-like (DBL) domain, unique to Plasmodium species. The two Plasmodium species responsible for the majority of malaria disease in humans are P. falciparum and P. vivax. There are four identified EBL members in P. falciparum that contain two tandem DBL domains in RII. This organization contrasts the single DBL domain in RII of the only characterized EBL member of P. vivax, Duffy-binding Protein (PvDBP). Using a combination of structural, biophysical, and cellular interaction methods we examined the binding mode for these two Plasmodium EBL family members to define the molecular and mechanistic basis of unique red cell invasion routes. Specifically, we sought to enhance our understanding of the molecular and mechanistic details of invasion by Plasmodium EBL ligands with the ultimate goal of identifying novel targets for rational vaccination efforts. We examined receptor interactions of a P. falciparum EBL member, Erythrocyte-binding-antigen 140 (PfEBA-140) and P. vivax DBP to provide insight into invasion by both species of parasite. Our work identified unique interfaces on the DBL domain that provide specific recognition of each ligand's unique red blood cell receptor. Additionally, studies examining oligomeric state identified distinct mechanistic parameters for the two EBL ligands, and contrasted with the mechanism observed for another P. falciparum member, PfEBA-175.
Download or read book Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
Download or read book Malaria written by Irwin W. Sherman and published by Amer Society for Microbiology. This book was released on 1998-01 with total page 575 pages. Available in PDF, EPUB and Kindle. Book excerpt: Every 30 seconds a death is caused by Malaria. This book brings together recent advances in our understanding of the basic biology, genetics and pathogenesis of malaria, to facilitate the rapid generation of new insights and interventions. Each chapter is written by a leading expert(s), and serves as both a useful introduction to the area and a helpful set of references. Malaria: Parasite Biology, Pathogenesis and Protection is a useful entry point for graduate and medical students, scientists and individuals engaged in a subspecialty of Malaria research, as well as those who are simply interested in getting a grasp on the present status of this ever burgeoning public health problem.
Download or read book Molecular Mechanisms of Parasite Invasion written by Barbara A. Burleigh and published by Springer Science & Business Media. This book was released on 2008-12-05 with total page 255 pages. Available in PDF, EPUB and Kindle. Book excerpt: All of the parasitic organisms highlighted in this new book represent medically important human pathogens that contribute significantly to the global burden of disease. As such there is intense interest in understanding the molecular basis of infection by these pathogens—not only with regard to their clinical relevance but also the fascinating biology they reveal. For most of the parasites discussed here the ability to penetrate biological barriers and/or to establish intracellular residence is critical to survival of the pathogen in the mammalian hosts. For other parasites, a tissue invasive phenotype is a key virulence determinant. In the ensuing 18 chapters, select members of this diverse set of protozoan parasites, as well as some examples of the extremely reduced fungal parasites classified as Microsporidia, are discussed within the context of the fascinating molecular strategies employed by these organisms to migrate across biological barriers and to establish residence within target host cells.
Download or read book Malaria written by Mats Wahlgren and published by CRC Press. This book was released on 2003-09-02 with total page 576 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria causes more death and disease than any other parasitic pathogen known today. This multiauthored text covers the important areas of malaria research, particularly focusing on those sectors which are of clinical importance for the understanding of the disease, the parasite, and its vector. The chapter authors are all leading experts within their own particular fields. The biology and molecular biology of the parasite, the clinical spectrum of the disease, the pathogenesis of malaria, and the immunology and emergence of malaria vaccines are some examples of the scientific spheres that are discussed. The book is suitable as a text for graduate students and clinicians as well as researchers at universities and companies involved in treating or studying infectious diseases.
Download or read book Encyclopedia of Malaria written by and published by Springer. This book was released on 2018-07-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Encyclopedia of Malaria represents a vast databank of information about the study of malaria. It provides an overview of the historical, rapid and significant developments that have occurred in malaria research, including the 2002 genome sequencing of Plasmodium falciparum and its mosquito vector, Anopheles gambiae. This work provides a concise source of up-to-date research findings in the form of definitions and essays and present comprehensive coverage of topics from history to findings to diagnosis and treatment, written by recognized malaria researchers with practical experience. It appeals to a diverse audience, including malaria researchers, teachers, investigators and public health professionals.
Download or read book Molecular Mechanisms of Protein Export by the Malaria Parasite Plasmodium Falciparum written by Bianca Bana and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Rodent Malaria written by R. Killick-Kendrick and published by Elsevier. This book was released on 2012-12-02 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rodent Malaria reviews significant findings concerning malaria parasites of rodents, including their taxonomy, zoogeography, and evolution, along with life cycles and morphology; genetics and biochemistry; and concomitant infections. This volume is organized into eight chapters and begins by sketching out the history of the discovery of rodent as well as aspects of parasitology, immunology, and chemotherapy. These concepts are investigated two decades following Ignace Vincke's major discovery and Meir Yoeli's successful establishment of the method of cyclical transmission of the parasite. The following chapters focus on the taxonomy and systematics of the subgenus Vinckeia, with reference to the concepts of species and subspecies of animals and the degree to which they apply to malaria parasites, in particular to those of rodents. The discussion then shifts to how the rodent malaria parasites provide a unique insight into the subcellular organization of Plasmodium species, the use of rodent malaria as an experimental model to study immunological responses, and infectious agents that interact with malaria parasites. The book concludes with a chapter on malaria chemotherapy, with emphasis on the value of rodent malaria in antimalarial drug screening and the use of antimalarial drugs as biological probes. This book will be of interest to protozoologists and physicians as well as those from other disciplines including biochemistry, immunology, pharmacology, cell biology, and genetics.
Download or read book Development of Novel Chemical Biology Tools to Probe Malaria Parasite Physiology and Aid in Antimalarial Drug Discovery written by James Robbins Abshire and published by . This book was released on 2015 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria remains a major burden to global public health. Antimalarial drugs are a mainstay in efforts to control and eventually eradicate this disease. However, increasing drug resistance threatens to reverse recent gains in malaria control, making the discovery of new antimalarials critical. Antimalarial discovery is especially challenging due to the unique biology of malaria parasites, the scarcity of tools for identifying new drug targets, and the poorly understood mechanisms of action of existing antimalarials. Therefore, this work describes the development of two chemical biology tools to address unmet needs in antimalarial drug discovery. A particular challenge in antimalarial development is a shortage of validated parasite drug targets. Potent antimalarials with demonstrated clinical efficacy, like the aminoquinolines and artemisinins, represent a promising basis for rational drug development. Unfortunately, the molecular targets of these drugs have not been identified. While both are thought to interact with parasite heme, linking in vitro heme binding with drug potency remains challenging because labile heme is difficult to quantify in live cells. This work presents a novel genetically-encoded heme biosensor and describes its application to quantify labile heme in live malaria parasites and test mechanisms of antimalarial action. Another challenge is posed by the widespread malaria parasite Plasmodium vivax, which, unlike P. falciparum, cannot be propagated in vitro, hindering research into parasite biology and drug target identification. P. vivax preferentially invades reticulocytes, which are impractical to obtain in continuous supply. The basis for this invasion tropism remains incompletely understood, mainly because current tools cannot directly link molecular binding events to invasion outcomes. This work presents novel methods for immobilizing synthetic receptors on the red blood cell surface. These receptors are used in proof-of-concept experiments to investigate requirements for efficient invasion via a well-characterized P. falciparum invasion pathway, suggesting this method can be used to elucidate molecular mechanisms underlying parasite invasion tropisms. Future receptor designs could promote the invasion of P. vivax into mature red blood cells and potentially facilitate practical in vitro culture. Taken together, these tools present new opportunities for drug discovery to aid efforts in malaria control and eventual eradication.
Download or read book Analysis of the Molecular Mechanisms Underlying Genomic Maintenance in the Malaria Parasite Plasmodium Falciparum written by Jeffrey S. Buguliskis and published by . This book was released on 2007 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Advances in Malaria Research written by Deepak Gaur and published by John Wiley & Sons. This book was released on 2016-12-27 with total page 611 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly reviews our current understanding of malarial biology Explores the subject with insights from post-genomic technologies Looks broadly at the disease, vectors of infection, and treatment and prevention strategies A timely publication with chapters written by global researchers leaders
Download or read book Complement Receptor 1 Is a Sialic Acid Independent Erythrocyte Receptor of Plasmodium Falciparum written by and published by . This book was released on 2010 with total page 24 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1-coated microspheres. Also, the invasion of neuraminidase treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a long standing and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine.
Download or read book Cellular and Molecular Mechanisms of Plasmodium Parasite Sensing and Immune Activation in Severe Malaria written by Emily Spaulding and published by . This book was released on 2015 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Molecular Mechanisms of Complement Evasion by Asexual Blood Stages and Infective Sporozoites of Plasmodium Falciparum written by Thiago Ferreira de Araujo Rosa and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Infectious Disease and Host Pathogen Evolution written by Krishna R. Dronamraju and published by Cambridge University Press. This book was released on 2004-04-05 with total page 394 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, originally published in 2004, is concerned with the links between human evolution and infectious disease. It has long been recognised that an important factor in human evolution has been the struggle against infectious disease and, more recently, it was revealed that complex genetic polymorphisms are the direct result of that struggle.
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 Malaria Immunology written by Peter Perlmann and published by Karger Medical and Scientific Publishers. This book was released on 2002-01-01 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite extensive efforts to control it, malaria is still one of the most devastating infectious diseases worldwide. This book, now in its second edition, provides a broad and up-to-date overview of the rapidly expanding field of malaria immunology and its importance in the control of this disease. The first section deals with the malaria parasite and its interactions with both the vertebrate host and the mosquitoes which transmit the disease. In the second part, the mechanisms of immunity and their regulation by environmental and genetic factors are discussed. Finally, this volume contains several chapters on malaria vaccine development, describing the application of the most recent vaccine technologies as well as ongoing and planned vaccine trials. Authored by well-recognized experts, this volume not only demonstrates the rapid progress being made in the search for vaccines against malaria, but also broadens our understanding of immunity to infection in general. It is therefore highly recommended reading for all scientists and professionals in the fields of immunology, infection and vaccine development.
