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This is an insiders account of 50 years of genetic studies of the soil-inhabiting microbes that produce most of the antibiotics used to treat infections, as well as anti-cancer, anti-parasitic and immunosuppressant drugs. The book begins by describing how these microbes the actinomycetes were discovered in the latter part of the nineteenth century, but remained a Cinderella group until, in the 1940s, they shot to prominence with the discovery of streptomycin, the first effective treatment for tuberculosis and only the second antibiotic, after penicillin, to become a medical marvel. There followed a massive effort over several decades to find further treatments for infectious diseases and cancer, tempered by the rise of antibiotic resistance consequent on antibiotic misuse and over-use. The book goes on to describe the discovery of gene exchange in the actinomycetes in the context of the rise of microbial genetics in the mid-20th century, leading to determination of the complete DNA sequence of a model member of the group at the turn of the millennium. There follow chapters in which the intricate molecular machinery that adapts the organisms metabolism and development to life in the soil, including antibiotic production, is illuminated by the DNA blueprint. Then come an up-to-the minute account of the use of genetic engineering to make novel, hybrid, antibiotics, and a topical description of techniques to learn the roles of the thousands of genes in a genome sequence, throwing a powerful light on the biology of the organisms and their harnessing for increasing antibiotic productivity. In the final chapter we return to the mycobacteria that cause tuberculosis and leprosy, the first actinomycetes to be discovered, and how methodology, in part derived from the study of the streptomycetes, is being applied to understand and control these still deadly pathogens.
This is an insiders account of 50 years of genetic studies of the soil-inhabiting microbes that produce most of the antibiotics used to treat infections, as well as anti-cancer, anti-parasitic and immunosuppressant drugs. The book begins by describing how these microbes the actinomycetes were discovered in the latter part of the nineteenth century, but remained a Cinderella group until, in the 1940s, they shot to prominence with the discovery of streptomycin, the first effective treatment for tuberculosis and only the second antibiotic, after penicillin, to become a medical marvel. There followed a massive effort over several decades to find further treatments for infectious diseases and cancer, tempered by the rise of antibiotic resistance consequent on antibiotic misuse and over-use. The book goes on to describe the discovery of gene exchange in the actinomycetes in the context of the rise of microbial genetics in the mid-20th century, leading to determination of the complete DNA sequence of a model member of the group at the turn of the millennium. There follow chapters in which the intricate molecular machinery that adapts the organisms metabolism and development to life in the soil, including antibiotic production, is illuminated by the DNA blueprint. Then come an up-to-the minute account of the use of genetic engineering to make novel, hybrid, antibiotics, and a topical description of techniques to learn the roles of the thousands of genes in a genome sequence, throwing a powerful light on the biology of the organisms and their harnessing for increasing antibiotic productivity. In the final chapter we return to the mycobacteria that cause tuberculosis and leprosy, the first actinomycetes to be discovered, and how methodology, in part derived from the study of the streptomycetes, is being applied to understand and control these still deadly pathogens.
This book presents an introductory overview of Actinobacteria with three main divisions: taxonomic principles, bioprospecting, and agriculture and industrial utility, which covers isolation, cultivation methods, and identification of Actinobacteria and production and biotechnological potential of antibacterial compounds and enzymes from Actinobacteria. Moreover, this book also provides a comprehensive account on plant growth-promoting (PGP) and pollutant degrading ability of Actinobacteria and the exploitation of Actinobacteria as ecofriendly nanofactories for biosynthesis of nanoparticles, such as gold and silver. This book will be beneficial for the graduate students, teachers, researchers, biotechnologists, and other professionals, who are interested to fortify and expand their knowledge about Actinobacteria in the field of Microbiology, Biotechnology, Biomedical Science, Plant Science, Agriculture, Plant pathology, Environmental Science, etc.
With contributions from some of the leading scientists in the field, this volume documents recent research and development in streptomycetes genomics, physiology and metabolism. With a focus on biotechnology and genomics, the book provides an excellent source of up-to-date information. Topics include: genome architecture, conjugative genetic elements, differentiation, protein secretion, central carbon metabolic pathways, regulation of nitrogen assimilation, phosphate control of metabolism, gamma-butyrolactones and their role in antibiotic regulation, clavulanic acid and clavams, genome-guided.
Beyond being the most important natural compound source, actinomycetes are the origin of up to two-thirds of all clinically used antibiotics. Currently, new antimicrobials are urgently needed, as infections caused by antibiotic-resistant pathogens are on the rise. In the identification of new antibiotics, many scientists are currently investigating biosynthetic aspects of antibiotic production in actinomycetes. Since the emergence of next-generation sequencing technologies, the field of antibiotics research has experienced a remarkable revival. These bacteria have the potential to produce more antibiotics than previously thought possible. Some antibiotics are produced in standard media, while others require the presence of a specific signaling molecule in the medium. Others, however, are only produced when the native regulation of the biosynthesis gene cluster is overruled. This book covers topics in the field of antibiotic-producing actinomycetes. The following tops are addressed: - Approaches to access novel antibiotic producers for novel natural compounds - Omics and genome mining approaches for the discovery of novel natural compounds - Analyses and genetic engineering of antibiotic biosynthesis - Regulation of the secondary metabolism in actinomycetes
We often think of scientists as dispassionate and detached, nobly laboring without any expectation of reward. But scientific research is much more complicated and messy than this ideal, and scientists can be torn by jealousy, impelled by a need for recognition, and subject to human vulnerability and fallibility. In Prize Fight , Emeritus Chair at SUNY School of Medicine Morton Meyers pulls back the curtain to reveal the dark side of scientific discovery. From allegations of stolen authorship to fabricated results and elaborate hoaxes, he shows us how too often brilliant minds are reduced to petty jealousies and promising careers cut short by disputes over authorship or fudged data. Prize Fight is a dramatic look at some of the most notable discoveries in science in recent years, from the discovery of insulin, which led to decades of infighting and even violence, to why the 2003 Nobel Prize in Medicine exposed how often scientific objectivity is imperiled.
Actinobacteria have an extensive bioactive secondary metabolism and produce a huge amount of naturally derived antibiotics, as well as many anticancer, anthelmintic, and antifungal compounds. These bacteria are of major importance for biotechnology, medicine, and agriculture. In this book, we present the experience of worldwide specialists in the field of Actinobacteria, exploring their current knowledge and future prospects.
Streptomyces is the most important bacterial genus for bioactive compound production. These soil bacteria are characterized by a complex differentiation cycle. Streptomyces is extremely important in biotechnology, producing approximately two thirds of all antibiotics, as well as many compounds of medical and agricultural interest. Drug discovery from streptomycetes became challenging once the most common compounds were discovered, and the system was basically abandoned by industry. Simultaneously, antibiotic resistance is increasing dramatically, and new antibiotics are required. Screening from nature is being resumed (exploring new environments, looking for elicitors, metagenome, etc.). Secondary metabolism is conditioned by differentiation; although the relationship between both has long remained elusive, differentiation as a trigger for antibiotic production remains basically unexplored. Most cultures used in screening campaigns for new bioactive molecules have been performed empirically, and workflow was extremely productive during the so-called golden age of antibiotics; however, currently there is a bottleneck. Streptomyces is still the most important natural source of antibiotics, and it also harbors many cryptic secondary metabolite pathways not expressed under laboratory conditions. In this chapter, we review strategies based on differentiation, one of the keys improving secondary metabolite production and activating cryptic pathways to face the challenges of drug discovery.
Antimicrobial agents are essential for the treatment of life-threatening infections and for managing the burden of minor infections in the community. In addition, they play a key role in organ and bone marrow transplantation, cancer chemotherapy, artificial joint and heart valve surgery. Unlike other classes of medicines, they are vulnerable to resistance from mutations in target microorganisms, and their adverse effects may extend to other patients (increased risk of cross-infection). As a consequence, there is a constant requirement for new agents, as well as practices that ensure the continued effective prescribing of licensed agents. Public awareness and concerns about drug resistant organisms has led to widespread publicity and political action in the UK, Europe and worldwide. The control of drug resistance and the implementation of good prescribing practice are now legal requirements in the UK as a result of the UK Health Act (2008). These fundamental changes underscore the need for a thorough understanding of the advantages and risks associated with specific antibiotic choices. This sixth edition of Antimicrobial Chemotherapy continues to be a valuable resource for undergraduates and graduates requiring a thorough grounding in the scientific basis and clinical application of these drugs. This new edition is updated to include the most recently licensed agents, notably in the treatment of viral infections including HIV/AIDS, and contains new guidance on prescribing practice and infection control practices that limit the development and spread of resistant organisms.