Unraveling Carbohydrate-mediated Host-pathogen Interactions PDF Download

Author: Jing Shang
Publisher:
ISBN:
Category :
Languages : en
Pages : 135

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Book Description
Infectious diseases present a significant challenge to public health, and there is an urgent need to develop new strategies to address bacterial and viral pathogenesis. As the initial interaction between pathogen and the host cell is often mediated by a carbohydrate recognition event, a straightforward and effective strategy to prevent infection is to block host-pathogen protein-carbohydrate binding. By mimicking carbohydrate ligands present on the host mucosa, human milk glycans have been proven to function as soluble inhibitors capable of preventing a variety of pathogens from binding to the host. These glycans hold great promise to be employed as anti-infective prophylactics to combat infectious disease in both pediatric and adult populations. However, among the hundreds of carbohydrate structures found in human milk, it is challenging to establish the inhibitory relationship between discrete glycan entities and specific pathogens. To address this problem and accelerate the development of anti-infective glycans, we apply high-throughput and label-free biosensing platforms for characterizing the anti-viral activities of human milk glycans against norovirus and HIV. Surface plasmon resonance (SPR) and silicon photonic microring resonators are two types of label-free biosensors capable of quantifying binding events in real-time. However, the lack of efficient biofunctionalization strategies limits the application of these devices in characterizing carbohydrate-mediated interactions. In this study, reliable and versatile conjugation methods were developed to functionalize biosensors with carbohydrates. These methods utilize a homobifunctional linker, divinylsulfone (DVS), to conjugate natural sugars or carbohydrates modified with nucleophilic linkers ( -NH2, -SH) onto the sensor surface. Compared to previous immobilization strategies, our DVS-based method greatly simplifies the process for carbohydrate immobilization and demonstrates high stability for biosensing. Next, the carbohydrate-functionalized biosensors were applied to study human milk glycan-norovirus interactions. We identified glycans that bind to two strains of norovirus and confirmed the activity of specific glycans against norovirus-host receptor interactions. Finally, the inhibitory mechanism of human milk glycosaminoglycans (GAGs) against HIV infection was investigated by SPR. The biosensing platforms and the binding studies in this dissertation advance our understanding of the anti-infective mechanism of human milk glycans and promote the application of glycan-based agents to prevent norovirus and HIV infection.

Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309096014
Category : Medical
Languages : en
Pages : 306

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Book Description
Infectious diseases have existed longer than us, as long as us, or are relatively newer than us. It may be the case that a disease has existed for many, many years but has only recently begun affecting humans. At the turn of the century the number of deaths caused by infections in the United States had been falling steadily but since the '80s has seen an increase. In the past 30 years alone 37 new pathogens have been identified as human disease threats and 12% of known human pathogens have been classified as either emerging or remerging. Whatever the story, there is currently a "war" on infectious diseases. This war is simply the systematic search for the microbial "cause" of each disease, followed by the development of antimicrobial therapies. The "war" on infectious diseases, however, must be revisited in order to develop a more realistic and detailed picture of the dynamic interactions among and between host organisms and their diverse populations of microbes. Only a fraction of these microbes are pathogens. Thus, in order to explore the crafting of a new metaphor for host-microbe relationships, and to consider how such a new perspective might inform and prioritize biomedical research, the Forum on Microbial Threats of the Institute of Medicine (IOM) convened the workshop, Ending the War Metaphor: The Changing Agenda for Unraveling the Host-Microbe Relationship on March 16-17, 2005. Workshop participants examined knowledge and approaches to learning about the bacterial inhabitants of the human gut, the best known host-microbe system, as well as findings from studies of microbial communities associated with other mammals, fish, plants, soil, and insects. The perspective adopted by this workshop is one that recognizes the breadth and diversity of host-microbe relationships beyond those relative few that result in overt disease. Included in this summary are the reports and papers of individuals participating in the Forum as well as the views of the editors.

Author: Simon Wong
Publisher: Springer Science & Business Media
ISBN: 9780306478444
Category : Medical
Languages : en
Pages : 336

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Book Description
This book is unique in providing pertinent information on the various established roles carbohydrate play in the immune system and how the innate and adaptive immune systems respond to this type of microbial antigens. The editors selected only topics that have established basic and clinical relevance to this field. The topics from basic research are organised like a textbook, in order to guide the readers through complex sets of events that lead to clearance of or to immune responses toward carbohydrate antigens. The book is clear, concise and contains fully annotated summaries of the key basic and practical information on carbohydrate immunology from current literature. These topics are written by investigators from various disciplines (chemistry, medicine, biochemistry, glycobiology and immunology), creating a fine balance in the point of views presented in the book. It explores the challenges and rewards of understanding the importance of carbohydrates and glycoconjugates in health and disease, applying new knowledge from carbohydrate immunology in improving or developing novel sugar-based therapeutics, and vaccines and medicines. This book is most suitable for glycobiologists and immunologists, but many researchers whose interests, background and expertise are in any of the fifteen topics presented in this book will also find it appealing. It is also a valuable resource for postgraduate students, clinicians or anyone else who is curious about the role of carbohydrates in immunology, and would like to see the topics combined under one cover and in relation to each other.

Author: Delphine Vincent
Publisher: Frontiers Media SA
ISBN: 2889450872
Category :
Languages : en
Pages : 190

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Book Description
Secretomics describes the global study of proteins that are secreted by a cell, a tissue or an organism, and has recently emerged as a field for which interest is rapidly growing. The term secretome was first coined at the turn of the millennium and was defined to comprise not only the native secreted proteins released into the extracellular space but also the components of machineries for protein secretion. Two secretory pathways have been described in fungi: i) the canonical pathway through which proteins bearing a N-terminal peptide signal can traverse the endoplasmic reticulum and Golgi apparatus, and ii) the unconventional pathway for proteins lacking a peptide signal. Protein secretion systems are more diverse in bacteria, in which types I to VII pathways as well as Sec or two-arginine (Tat) pathways have been described. In oomycete species, effectors are mostly small proteins containing an N-terminal signal peptide for secretion and additional C-terminal motifs such as RXLRs and CRNs for host targeting. It has recently been shown that oomycetes exploit non-conventional secretion mechanisms to transfer certain proteins to the extracellular environment. Other non-classical secretion systems involved in plant-fugal interaction include extracellular vesicles (EVs, Figure 1 from Samuel et al 2016 Front. Plant Sci. 6:766.). The versatility of oomycetes, fungi and bacteria allows them to associate with plants in many ways depending on whether they are biotroph, hemibiotroph, necrotroph, or saprotroph. When interacting with a live organism, a microbe will invade its plant host and manipulate its metabolisms either detrimentally if it is a pathogen or beneficially if it is a symbiote. Deciphering secretomes became a crucial biological question when an increasing body of evidence indicated that secreted proteins were the main effectors initiating interactions, whether of pathogenic or symbiotic nature, between microbes and their plant hosts. Secretomics may help to contribute to the global food security and to the ecosystem sustainability by addressing issues in i) plant biosecurity, with the design of crops resistant to pathogens, ii) crop yield enhancement, for example driven by arbuscular mycorrhizal fungi helping plant hosts utilise phosphate from the soil hence increase biomass, and iii) renewable energy, through the identification of microbial enzymes able to augment the bio-conversion of plant lignocellulosic materials for the production of second generation biofuels that do not compete with food production. To this day, more than a hundred secretomics studies have been published on all taxa and the number of publications is increasing steadily. Secretory pathways have been described in various species of microbes and/or their plant hosts, yet the functions of proteins secreted outside the cell remain to be fully grasped. This Research Topic aims at discussing how secretomics can assist the scientists in gaining knowledge about the mechanisms underpinning plant-microbe interactions.

Author: C.I. Kado
Publisher: Springer Science & Business Media
ISBN: 9401107467
Category : Science
Languages : en
Pages : 676

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Book Description
The growing body of information on bacteria pathogenic for humans, mammals and plants generated within the past ten years has shown the interesting conservation of newly identified genes that playa direct role in the pathogenic mechanism. In addition to these genes, there are also genes that confer host specificities and other traits important in pathogenesis on these pathogens. In this volume, we have organized the subject areas to best fit the concept on the way bacterial pathogens recognize, interact and invade the host, on the regulation of genes involved in virulence, on the genes involved in the elaboration of toxins and other pathogenic components such as iron sequestering proteins, and on the mechanisms of circumventing the host defense systems. These areas are divided into Sections. Section I covers the first step when the pathogen seeks its host, and Sections II through VI cover subsequent steps leading to pathogenesis while avoiding host defenses. We conclude this work with a chapter summarizing information on examples of virulence mechanisms that are highly conserved.

Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309264324
Category : Medical
Languages : en
Pages : 633

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Book Description
Beginning with the germ theory of disease in the 19th century and extending through most of the 20th century, microbes were believed to live their lives as solitary, unicellular, disease-causing organisms . This perception stemmed from the focus of most investigators on organisms that could be grown in the laboratory as cellular monocultures, often dispersed in liquid, and under ambient conditions of temperature, lighting, and humidity. Most such inquiries were designed to identify microbial pathogens by satisfying Koch's postulates.3 This pathogen-centric approach to the study of microorganisms produced a metaphorical "war" against these microbial invaders waged with antibiotic therapies, while simultaneously obscuring the dynamic relationships that exist among and between host organisms and their associated microorganisms-only a tiny fraction of which act as pathogens. Despite their obvious importance, very little is actually known about the processes and factors that influence the assembly, function, and stability of microbial communities. Gaining this knowledge will require a seismic shift away from the study of individual microbes in isolation to inquiries into the nature of diverse and often complex microbial communities, the forces that shape them, and their relationships with other communities and organisms, including their multicellular hosts. On March 6 and 7, 2012, the Institute of Medicine's (IOM's) Forum on Microbial Threats hosted a public workshop to explore the emerging science of the "social biology" of microbial communities. Workshop presentations and discussions embraced a wide spectrum of topics, experimental systems, and theoretical perspectives representative of the current, multifaceted exploration of the microbial frontier. Participants discussed ecological, evolutionary, and genetic factors contributing to the assembly, function, and stability of microbial communities; how microbial communities adapt and respond to environmental stimuli; theoretical and experimental approaches to advance this nascent field; and potential applications of knowledge gained from the study of microbial communities for the improvement of human, animal, plant, and ecosystem health and toward a deeper understanding of microbial diversity and evolution. The Social Biology of Microbial Communities: Workshop Summary further explains the happenings of the workshop.

Author: René Roy
Publisher: ACS Symposium
ISBN: 9780841239838
Category : Science
Languages : en
Pages : 0

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Book Description
This book is the first of its kind entirely dedicated to carbohydrate vaccines written by renowned scientists with expertise in carbohydrate chemistry and immunochemistry. It covers the synthesis of carbohydrate antigens related to bacteria and parasites such as: Heamophilus influenza, Streptococcus pnemoniae, Shigella flexneri, Candida albicans, Mycobacterium tuberculosis, and Chlamydia. The first three chapters are of wide interest as they cover fundamental concerns in new vaccine developments. The first one presents the immune system and how carbohydrate antigens are processed before protective antibodies are produced. It also illustrates antigen presentation in the context of major histocompatibility complexes (MHCs). The second chapter describes regulatory issues when carbohydrate vaccines are involved while the third one discuss several techniques used in conjugation chemistry and the implication of certain chemical linkages that may induce unexpected anti-linker antibodies. This section will be particularly appealing for those involved in drug-conjugate design, pro-drug developments, and drug vectorization. The book concludes with one chapter that illustrates the principle through which peptide antigens can functionally mimic carbohydrate epitopes, thus, unraveling the potential for peptide surrogates as replacement for complex carbohydrate structures. This book is unique in that it covers all aspects related to carbohydrate vaccines including the success story with the first semi-synthetic bacterial polysaccharide vaccine against Heamophilus influenza type b responsible for pneumonia and meningitis, liable for more than 600,000 infant deaths worldwide in developing countries. The book also presents regulatory issues and will thus be vital for government agencies approving candidate vaccines. It widely covers synthetic methodologies for the attachment of carbohydrate antigens to peptides and immunogenic protein carriers. Vaccines against bacterial antigens, cancer, and parasites are also discussed by worldwide experts in this field in details. No other book contains such a wide panel of different expertise. It will also be useful to students and researchers involved with the immunology of forreings antigens and how the under appreciated carbohydrate antigens are processed by the immune system.

Author: Thisbe K. Lindhorst
Publisher: Springer Science & Business Media
ISBN: 3642013031
Category : Science
Languages : en
Pages : 194

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Book Description
bacterial carbohydrate recognition are conveyed, covering Gram-positive as well as Gram-negative bacteria, in Chapter 4 Streptococci and Staphylococci, and in Chapter 5, carbohydrate binding specificities of Helicobacter pylori. In Chapter 6, "Bitter sweetness of complexity," the collected reflections on mic- bial adhesion are expanded by a perspective on a broader impact of glycosylation on cellular adhesion, motility and regulatory processes, paralleling the complexity of N-glycan structures on cell surfaces. It highlights particularly how structural details of N-glycans have been causally related to pathological scenarios, with a focus on ?(1,6)-N-acetylglucosaminyltransferase. In the final chapter, biofilm formation is reviewed, covering knowledge about structure and biosynthesis of polysaccharide intercellular adhesins (PIAs) which are central to biofilm formation. This comprehensive chapter explains all PIA-related principles of medical device-associated infections. It is our hope, that this collection of expert articles, ranging from structural ch- istry and structural biology to biochemistry and medicine, will be a stimulation and motivation for our colleagues in the life sciences. At the same time, we hope that these reflections on microbial adhesion will awake interest in and promote und- standing of the complex processes associated with the glycocalyx and the multif- eted interactions between the host cell and its "guest," as well as the biological consequences resulting from this mutual interplay.

Author: Dinesh Chandra
Publisher: Academic Press
ISBN: 0323985327
Category : Science
Languages : en
Pages : 316

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Book Description
Unravelling Plant-Microbe Synergy focuses on agriculturally important microorganisms (AIM’s) that are indigenous to soil and roots of the plant. These microbes contributing to nutrient balance, growth regulators, suppressing pathogens, alleviate stress response, orchestrating immune response and improving crop performance as they are offering sustainable and alternative solutions to the use of chemicals in agriculture. As plant microbe synergy is an enthralling subject, is multidisciplinary in nature, and concerns scientists involved in applied, and environmental microbiology and plant health and plant protection, Unravelling Plant-Microbe Synergy is an ideal resource that emphasizes the current trends of, and probable future of, microbes mediated amelioration of abiotic and biotic stress, agriculture sustainability, induced systemic tolerance and plant health protection. Unravelling Plant-Microbe Synergy discloses the microbial interaction for stress management and provides a better understanding to know the recent mechanisms to cope these environmental stresses. Unravelling Plant-Microbe Synergy bridges the gap in recent advances in the microbes interaction and rhizosphere engineering. Emphasizes the plant microbes interactions, induced systemic tolerance, stress responsive genes and diversity of microorganisms Illustrates the current impact of climate change on plant productivity along with mitigation strategies Provides a two-way interactive approach to both plants and microbes, and includes multi-omics approaches

Author: Ajit Varki
Publisher: CSHL Press
ISBN: 9780879696818
Category : Medical
Languages : en
Pages : 694

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Book Description
Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.