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Phage Therapy: Past; Present and Future

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452514 Year: Pages: 392 DOI: 10.3389/978-2-88945-251-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2018-02-27 16:16:44
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Historically, the first observation of a transmissible lytic agent that is specifically active against a bacterium (Bacillus anthracis) was by a Russian microbiologist Nikolay Gamaleya in 1898. At that time, however, it was too early to make a connection to another discovery made by Dmitri Ivanovsky in 1892 and Martinus Beijerinck in 1898 on a non-bacterial pathogen infecting tobacco plants. Thus the viral world was discovered in two of the three domains of life, and our current understanding is that viruses represent the most abundant biological entities on the planet. The potential of bacteriophages for infection treatment have been recognized after the discoveries by Frederick Twort and Felix d’Hérelle in 1915 and 1917. Subsequent phage therapy developments, however, have been overshadowed by the remarkable success of antibiotics in infection control and treatment, and phage therapy research and development persisted mostly in the former Soviet Union countries, Russia and Georgia, as well as in France and Poland. The dramatic rise of antibiotic resistance and especially of multi-drug resistance among human and animal bacterial pathogens, however, challenged the position of antibiotics as a single most important pillar for infection control and treatment. Thus there is a renewed interest in phage therapy as a possible additive/alternative therapy, especially for the infections that resist routine antibiotic treatment. The basis for the revival of phage therapy is affected by a number of issues that need to be resolved before it can enter the arena, which is traditionally reserved for antibiotics. Probably the most important is the regulatory issue: How should phage therapy be regulated? Similarly to drugs? Then the co-evolving nature of phage-bacterial host relationship will be a major hurdle for the production of consistent phage formulae. Or should we resort to the phage products such as lysins and the corresponding engineered versions in order to have accurate and consistent delivery doses? We still have very limited knowledge about the pharmacodynamics of phage therapy. More data, obtained in animal models, are necessary to evaluate the phage therapy efficiency compared, for example, to antibiotics. Another aspect is the safety of phage therapy. How do phages interact with the immune system and to what costs, or benefits? What are the risks, in the course of phage therapy, of transduction of undesirable properties such as virulence or antibiotic resistance genes? How frequent is the development of bacterial host resistance during phage therapy? Understanding these and many other aspects of phage therapy, basic and applied, is the main subject of this Topic.

Plants; Stress & Proteins

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452675 Year: Pages: 323 DOI: 10.3389/978-2-88945-267-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Botany
Added to DOAB on : 2018-02-27 16:16:44
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Biotic and abiotic stress factors deliver a huge impact on plant life. Biotic stress factors such as damage through pathogens or herbivore attack, as well as abiotic stress factors like variation in temperature, rainfall and salinity, have placed the plant kingdom under constant challenges for survival. As a consequence, global agricultural and horticultural productivity has been disturbed to a large extent. Being sessile in nature, plants cannot escape from the stress, and instead adapt changes within their system to overcome the adverse conditions. These changes include physiological, developmental and biochemical alterations within the plant body which influences the genome, proteome and metabolome profiles of the plant. Since proteins are the ultimate players of cellular behavior, proteome level alterations during and recovery period of stress provide direct implications of plant responses towards stress factors. With current advancement of modern high-throughput technologies, much research has been carried out in this field. This e-book highlights the research and review articles that cover proteome level changes during the course or recovery period of various stress factors in plant life. Overall, the chapters in this e-book has provided a wealth of information on how plants deal with stress from a proteomics perspective.

Molecular Pathogenesis of Pneumococcus

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452781 Year: Pages: 110 DOI: 10.3389/978-2-88945-278-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Internal medicine
Added to DOAB on : 2018-02-27 16:16:44
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Streptococcus pneumoniae has been for decades the number one bacterial killer of children in the world. Although vaccination with pneumococcal vaccines [PCV7, PCV10, and PCV13 (children) or PPSV23 (adults)] has helped decrease the burden of pneumococcal disease (PD), mortality remains high. Therefore, pathogenesis studies are still key toward our understanding of PD and its control. The introduction of pneumococcal vaccines has also created a niche for vaccine-escape clones. Moreover, the rise of multi-drug resistant clones around the world has also posed a serious threat in recent years. The proposed special issue of Frontiers in Cellular and Infection Microbiology highlights many of the recent advances that have been made in pneumococcal pathogenesis, colonization and antibiotic resistance by groups in Latino America, Europe, and the USA.

NETosis 2: The Excitement Continues

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453795 Year: Pages: 362 DOI: 10.3389/978-2-88945-379-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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NETosis, a form of cell death that manifests by the release of decondensed chromatin to the extracellular space, provides valuable insights into mechanisms and consequences of cellular demise. Because extracellular chromatin can immobilize microbes, the extended nucleohistone network was called a neutrophil extracellular trap (NET), and the process of chromatin release was proposed to serve an innate immune defense function. Extracellular chromatin NETs were initially observed in studies of neutrophils and are most prominent in these types of granulocytes. Subsequent studies showed that other granulocytes and, in a limited way, other cells of the innate immune response may also release nuclear chromatin following certain kinds of stimulation. Variations of NETosis were noted with cells that remain temporarily motile after the release of chromatin. Numerous stimuli for NETosis were discovered, including bacterial breakdown products, inflammatory stimuli, particulate matter, certain crystals, immune complexes and activated thrombocytes. Fundamental explorations into the mechanisms of NETosis observed that neutrophil enzyme activity (PAD4, neutrophil elastase, proteinase 3 and myeloperoxidase) and signal transduction pathways contribute to the regulation of NETosis. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases, leading to extensive chromatin externalization. In addition, NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. NETs are decorated with proteases and may thus contribute to tissue destruction. However, the attachment of these enzymes to NET-associated supramolecular structures restricts systemic spread of the proteolytic activity. While the benefit of NETs in an infection appears obvious, NETs also participate as key protagonists in various pathologic states. Therefore, it is essential for NETs to be efficiently cleared; otherwise digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions, serve as antigen for nuclear autoantibodies and foster DNA immune complex-related inflammation. Neutrophil products and deiminated proteins comprise an important group of autoantigens in musculoskeletal disorders. Aberrant NET synthesis and/or clearance are often associated with inflammatory and autoimmune conditions. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. Intravital microscopy provides evidence for conditions that induce NETosis in vivo. Furthermore, NETs can easily be detected in synovial fluid and tissue sections of patients with arthritis and gout. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we enter the second decade of research on NETosis, it is useful and timely to review the mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their importance as inducers of autoimmune responses.

Novel Pharmacological Inhibitors for Bacterial Protein Toxins

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ISBN: 9783038424314 9783038424307 Year: Pages: VI, 118 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Public Health --- Biology
Added to DOAB on : 2017-06-13 09:39:34
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Many medically relevant bacteria cause severe human and animal diseases because they produce and release protein toxins that target mammalian cells. Because the toxin-induced cell damage is the reason for the clinical symptoms, the targeted pharmacological inhibition of the cytotoxic mode of action of bacterial toxins should prevent or cure the respective toxin-associated disease. Toxin inhibitors might be beneficial when the toxin acts in the absence of the producing bacteria (e.g., food poisoning), but also in combination with antibiotics in infectious diseases when the toxin-producing bacteria are present. The focus of this Special Issue of Toxins is on the development and characterization of novel inhibitors against bacterial toxins, e.g., toxin neutralizing antibodies, peptides or small compounds, as well as toxin pore blockers, which interfere with bacterial toxins and thereby protect cells from intoxication.

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