The genus Pseudomonas represents a large group of medically and envi ronmentally important bacteria. Interest in these bacteria is reflected in the extensive number of publications devoted to original research, re views, and books on this subject. In this volume selected areas of Pseu domonas research are presented in depth by persons who have been active in their fields over many years. The extensive reviews presented are an effort to provide a balanced perspective in a number of areas not readily available in the current literature. In the style of the previous Biotechnology Handbooks most of these topics have not been reviewed at all, and several are also presented from a new direction. For example, in addition to structural and compositional aspects, the chapter on lipids provides shifts in lipid parameters that result from environmental changes. This information will be invaluable to a cross section of Pseu domonas researchers in pathogenesis and bioremediation. The chapters presented include basic aspects of plasmid biology and carbohydrate metabolism and regulation. A major emphasis is placed on the Pseudomonas aeruginosa cell surface. Chapters cover lipo polysaccharide, capsular polysaccharide and alginate, the outer mem brane, transport systems, and the flagellum. Uptake of iron is also neces sarily an important portion of the chapter on iron metabolism."

To the uninitiated, the genus Clostridium is likely more to be associated with disease than biotechnology. In this volume, we have sought to remedy this misconception by compiling aseries of chapters which, together, provide a practically-oriented handbook of the biotechnologie potential of the genus. Clostridium is a broad grouping of organisms that together undertake a myriad of biocatalytic reactions. In the first two chapters, the reader is introduced to this diversity, both taxonomically and physiologically. In the following chapter, the current state of genetic analysis of members of the genus is reviewed. The remaining chapters concentrate on specific, exploit able aspects of individual Clostridium species-highlighting their range of unique capabilities (of potential or recognized industrial value), particu larly in the areas of biotransformation, enzymology, and the production of chemical fuels. Fittingly, the final chapter demonstrates that even the most toxic of the clostridia can be of therapeutic value. The contributors to this volume reflect the trans national interest in Clostridium, and we are indebted to each of them for making this volume possible. We particularly wish to acknowledge the contributions, both to this volume and to microbiology in general, of Dr. Elizabeth Cato, who, sadly, died shortly be fore publication ofthis volume. Finally, we would like to join the authors in recommending closer and wider consideration of the attributes and capabilities of this genus."

2. The Translational Machinery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Translation Initiation in Prokaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Translation Initiation in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 14 Translation Elongation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Translation Termination in Prokaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Translation Termination in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Error Correction in Translation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 A Structural Basis of Error Correction in Translation . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Ribosome Editing: A Failsafe Error Correction Mechanism . . . . . . . . . . . . . . . . 22 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3. Errors During Elongation Can Cause Translational 29 Frameshifting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spontaneous Frameshifting Versus Programmed Frameshifting . . . . . . . . . . 30 Spontaneous Frameshifts Can Be Induced at Specific Codons . . . . . . . . . . . . 31 4. Programmed +1 Frameshifting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 The pifE Gene of E. coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Using the pifE System to Study General Frameshifting in E. coli . . . . . . . . 46 Ty Retrotransposons in Yeast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Frameshifting in Retrotransposon Ty1 Occurs by tRNA Slippage . . . . . . . 48 Frameshifting in Retrotransposon Ty3 Occurs by Out-of-Frame Binding of tRNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 The Rat Ornithine Decarboxylase Antizyme Gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 5. Programmed -1 Frameshifting in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Programmed -1 Frameshifting in Eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 -1 Frameshifting Occurs on a "Slippery Heptamer" . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 The Simultaneous-Slippage Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 of -1 Frameshifting by a Downstream Pseudoknot . . . . . . . . . . 77 Stimulation Does the Pseudoknot Only Block Passage of the Ribosome? . . . . . . . . . .

Hantaviruses are found world-wide and are associated with two severe disease syndromes, hemorrhagic fever and hantavirus pulmonary syndrome. The recent studies in this volume provide a basis for understanding the high human pathogenicity of theses viruses and their continued maintenance and transmission within rodent populations.

Virus Variability and Impact on Epidemiology and Control of Diseases E. Kurstak and A. Hossain I. INTRODUCTION An important number of virus infections and their epidemic developments demonstrate that ineffec tiveness of prevention measures is often due to the mutation rate and variability of viruses (Kurstak et al., 1984, 1987). The new human immunodeficiency retroviruses and old influenza viruses are only one among several examples of virus variation that prevent, or make very difficult. the production of reliable vaccines. It could be stated that the most important factor limiting the effectiveness of vaccines against virus infections is apparently virus variation. Not much is, how ever, known about the factors influencing and responsible for the dramatically diverse patterns of virus variability. II. MUTATION RATE AND VARIABILITY OF HUMAN AND ANIMAL VIRUSES Mutation is undoubtedly the primary source of variation, and several reports in the literature suggest that extreme variability of some viruses may be a consequence of an unusually high mutation rate (Holland et al., 1982; Domingo et al., 1985; Smith and Inglis, 1987). The mutation rate of a virus is defined as the probability that during a single replication of the virus genome a particular nucleotide position is altered through substitution, deletion, insertion. or recombination. Different techniques have been utilized to measure virus mutation rates, and these have been noted in the extent of application to different viruses."

Recently, there has been an upsurge in microbial infections. Extensive and inappropriate usage of antimicrobial drugs in treating infections has led to the evolution of a resistant strain of microorganisms and irreversible immunosuppression in humans. Medical institutions and hospitals require solutions to combat these contagions in order to avoid future epidemics. Strategies to Overcome Superbug Invasions: Emerging Research and Opportunities highlights current research and potential strategies to prevent the emergence and re-emergence of drug-resistant pathogenic microbial strains. The content within this publication examines biosensing, global initiatives, nanomaterials, and alternative therapies. It is designed for microbiologists, biotechnologists, pharmacists, pharmacologists, virologists, formulation scientists, infectious disease specialists, government officials, policymakers, healthcare practitioners, doctors, nurses, hospital directors, researchers, surgeons, and academicians who are seeking research on innovative solutions for multi-drug-resistant infections.

-Integration of Systems Biology with Bioprocess Engineering: L-Threonine Production by Systems Metabolic Engineering of Escherichia Coli, By Sang Yup Lee and Jin Hwan Park; -Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum, By Christoph Wittmann; -Systems Biology of Industrial Microorganisms, Marta Papini, Margarita Salazar, and Jens Nielsen; -De Novo Metabolic Engineering and the Promise of Synthetic DNA, By Daniel Klein-Marcuschamer, Vikramaditya G. Yadav, Adel Ghaderi, and Gregory N. Stephanopoulos; -Systems Biology of Recombinant Protein Production in Bacillus megaterium, Rebekka Biedendieck, Boyke Bunk, Tobias Furich, Ezequiel Franco-Lara, Martina Jahn, and Dieter Jahn; -Extending Synthetic Routes for Oligosaccharides by Enzyme, Substrate and Reaction Engineering; By Jurgen Seibel, Hans-Joachim Jordening, and Klaus Buchholz; -Regeneration of Nicotinamide Coenzymes: Principles and Applications for the Synthesis of Chiral Compounds; By Andrea Weckbecker, Harald Groger, and Werner Hummel;

Course covers topics in infectious diseases in children and is intended for Pediatric Infectious disease trainees, trainers, and all those who manage children with infections.

The oral cavity supports a rich and diverse microbial population. Oral health is dependent on the maintenance of stable microbial communities; disease occurs when this balance is disturbed and more pathogenic species outgrow the commensals. Health and disease in the mouth are active processes in which the ecology of communities, not of single organisms, is paramount. In this book, expert contributors from around the world provide an update on recent developments in the burgeoning field of oral microbial ecology. The chapters are arranged into five sections: microbial populations in oral biofilms, the structure of oral biofilms, communication and sensing within biofilms, health to disease, and new approaches for oral biofilm control.

Biologically active compounds isolated from microorganisms continue to be vital to the development of new drugs and agricultural chemicals. This book was prepared by current and past members of the laboratory of Dr. Satoshi Omura of the Kitasato Institute in Japan. Dr. Omura and his colleagues have discovered and studied a number of important antibiotics, and in their work they have pioneered new methods for screening microbes for interesting and important compounds. This book presents strategies and methods for identifying novel molecules with several types of biological activity. In addition, the book discusses the identification of microbial compounds of agrochemical importance, presents information on chemical screening methods, and concludes with chapters on microbial strain selection, fermentation technology, and genetic engineering of antibiotic-producing microorganisms. This book will be of great interest to scientists working in the very active and competitive fields of antibiotic and agrochemical discovery.

Authoritative investigators active in the discovery, development, and application of biological anti-infective agents concisely review their use and potential in preventing and treating human disease. Focusing on biotherapeutic entities that have been tested in controlled studies, the prominent experts illuminate the scientific underpinnings of their therapeutic power, assess their possible risks in the treatment of infectious diseases, and outline the research needed to better define their effectiveness. In addition, they also consider how biotherapeutic agents may be genetically engineered for maximum intestinal and vaginal production of bioactive substances in vivo. Biotherapeutic Agents and Infectious Diseases brings together all the evidence needed to understand and capitalize on the considerable promise of this significant new class of biotherapeutic entities.

There is a high demand for antimicrobials for the treatment of new and emerging microbial diseases. In particular, microbes developing multidrug resistance have created a pressing need to search for a new generation of antimicrobial agents, which are effective, safe and can be used for the cure of multidrug-resistant microbial infections. Nano-antimicrobials offer effective solutions for these challenges; the details of these new technologies are presented here.

The book includes chapters by an international team of experts. Chemical, physical, electrochemical, photochemical and mechanical methods of synthesis are covered. Moreover, biological synthesis using microbes, an option that is both eco-friendly and economically viable, is presented. The antimicrobial potential of different nanoparticles is also covered, bioactivity mechanisms are elaborated on, and several applications are reviewed in separate sections. Lastly, the toxicology of nano-antimicrobials is briefly assessed."

Years ago when we were asked to write a book on the present-day knowledge of the molecular biology of poliovirus, we did not expect that such an apparently simple task could involve so much time and effort. Our writing was hampered by the fact that both of us are full time "workers," so that this monograph is mainly a spare time expedience. The main attention of this book focuses on a detailed review of the molecular biology of poliovirus and especially on the advances of the last decade; medical and environmental aspects are only briefly mentioned. Observations from older studies are considered in view of more recent information. Some of the older ob servations provided fundamental insights and paved the way for present day research; too often such data has been neglected or independently rediscovered. Today, poliovirus research has again attracted considerable interest. High points gained within the last few years were the elucidation of the complete nucleotide sequences of the RNAs of the three poliovinls serotypes and the corresponding vaccine strains, the demonstration of genome evolution during transmission of poliovirus in an epidemic, further characterization of the antigenic sites on the virus particle and of the antigenic drift, characterization of alternate conforma tional states of the virion capsid, the development of monoclonal antibodies against some of the virus proteins, observations on the role of the plasma membrane, cytoskeleton, and cytoplasmic membranes as mediators in the virus induced redirection of the synthetic machinery of the host cell, and characteriza"

The ability to remember an antigenic encounter for several decades, even for a life time, is one of the fundamental properties of the immune system. This phenomenon known as "immunological memory," is the foundation upon which the concept if vaccination rests. Therefore, understanding the mechanisms by which immunological memory is regulated is of paramount importance. Recent advances in immunology, particularly in the field of innate immunity, suggest that the innate immune system plays fundamental roles in influencing immunological memory. Indeed, emerging evidence suggests that events that occur early, within hours if not minutes of pathogen or vaccine entry profoundly shape the quantity, quality and duration of immunological memory. The present volume assembles a collection of essays from leading experts that span the entire spectrum research from understanding the molecular mechanisms of innate immune recognition, to dendritic cell function, to the generation and maintenance of antigen-specific B and T-cell responses.

"Corynebacterium diphtheriae" is the classical etiological agent of diphtheria and the type strain of the genus "Corynebacterium." While diphtheria of the respiratory tract became rare with the introduction of vaccination programs in industrialized countries, even today several thousand cases per year are reported to the World Health Organization. This shows that diphtheria is not completely eradicated and that reservoirs exist. The book summarizes the latest advances made in understanding "C. diphtheriae" and the closely related species "Corynebacterium ulcerans" and" Corynebacterium pseudotuberculosis." Topics addressed are genomics of toxigenic corynebacteria, host-pathogen-interaction, detection, surveillance and treatment as well as application aspects.

The International Symposium on Frontiers in Microbiology has been de dicated to Prof. P. De Somer, whom I succeeded shortly after his death on 17 June 1985 as Rector of this now more than 560-year old University. When Prof. De Somer became the head of the University he started to remodel it, giving our old Alma Mater a more transparent administrative structure, strengthening its scientific and cultural autonomy, and establishing close links with the most prestigious national and foreign institutions. This made De Somer to one of the greatest, if not the greatest, of rectors in the history of Belgian Universities. He was a great leader, a perfect organizer, a clever negotiator, and a brilliant orator. In his speeches one immediately sensed his intuitive cognition and witty evaluation of the values of life. He knew perfectly well how to persuade the unwilling and to disenchant the illusionist. Sometimes a visionary himself, he would not pursue his ideas unless there was a chance of success. As innovative Prof. P. De Somer was in providing to this University a new face, or should I say facelifting, as international is his reputation as the founder, and, since its inception, only director, of the Rega Institute. Built now more than 30 years ago, the Rega Institute has re mained one of the world's leading centers in microbiological research."

Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.

Antiviral chemotherapy has come of age, and, after an initial slow pro gress, the development of new antiviral agents has proceeded at a more rapid pace and the perspectives for their clinical use have increased considerably. Now, 25 years after the first antiviral assay (idoxuridine) was introduced in the clinic, it is fitting to commemorate the beginning of the antivirals' era. In its introductory chapter B.E. Juel-Jensen touches on what may be con sidered as five of the most fundamental requirements of an antiviral drug: efficacy, relative non-toxicity, easy solubility, ready availability and rea sonable cost. Surely, the antiviral drugs that have so far been used in the clinic could still be improved upon as one or more of these five essential demands are concerned. How is all began is narrated by W.H. Prusoff. The first antiviral drugs to be used in humans were methisazone and idoxuridine, the former, which is now of archival interest, in the prevention of smallpox, the latter, which was approved for clinical use in the United States in 1962, for the topical treatment of herpetic keratitis. In terms of potency, also because of solubility reasons, idoxuridine has been superseded by trifluridine in the topical treatment of herpes simplex epithelial keratitis. H.E. Kaufman did not find trifluridine or acyclovir ef fective in the treatment of deep stromal keratitis or iritis and he reckons that other antiviral drugs (i.e. bromovinyldeoxyuridine) would not be effec tive either."

Nanoparticles for Gene Delivery into Stem Cells and Embryos, by Pallavi Pushp, Rajdeep Kaur, Hoon Taek Lee, Mukesh Kumar Gupta. Engineering of Polysaccharides via Nanotechnology, by Joydeep Dutta. Hydroxyapatite-Packed Chitosan-PMMA Nanocomposite: A Promising Material for Construction of Synthetic Bone, by Arundhati Bhowmick, Subhash Banerjee, Ratnesh Kumar, Patit Paban Kundu. Biodegradable Polymers for Potential Delivery Systems for Therapeutics, by Sanjeev K. Pandey, Chandana Haldar, Dinesh K. Patel, Pralay Maiti. Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics, by S. Maya, M. Sabitha, Shantikumar V. Nair, R. Jayakumar. Proteins and Carbohydrates as Polymeric Nanodrug Delivery Systems: Formulation, Properties and Toxicological Evaluation, by Dhanya Narayanan, J. Gopikrishna, Shantikumar V. Nair, Deepthy Menon. Biopolymeric Micro and Nanoparticles: Preparation, Characterization and Industrial Applications, by Anil Kumar Anal, Alisha Tuladhar. Applications of Glyconanoparticles as "Sweet" Glycobiological Therapeutics and Diagnostics, by Naresh Kottari, Yoann M. Chabre, Rishi Sharma, Rene Roy.

Although there are a number of excellent current reviews on one or another aspect of cytomegalovirus, the last comprehensive treatment of this subject was that of Krech et al. (197la). In view of the amazing advances in the virological, epidemiologic, and clinical knowledge of cytomegaloviruses, an up-to-date book is needed. Such a work should cover many areas of expertise and a voluminous technical literature. Each area might have been reviewed and analyzed by workers more expert than myself. However, I have embarked on the entire venture alone in order to attain unity and continuity in this book, characteristics that are not easily achieved in the more popular multiauthored works. I have tried to review the Iiterature and provide a critical summary for each area discussed. To do this, I provide as much of the primary data of the relevant works as needed and not just the qualitative conclusions. Inevitably, the flow of the narrative may be interrupted by dry facts and figures. However, such information is essential to make this a meaningful reference work. But for those not interested in such details, I have provided at what I hope are crucial points critiques and summaries. This book is not an exhaustive review of all the literature. This is probably no Ionger possible or even desirable. By selection, however, one runs the risk of having missed or ignored important papers. I am keenly aware of this, and I wish to apologize for such oversight, if that is possible.

Viral infections of the nervous system are important because they are associated with high morbidity and mortality. A variety of pathogenetic mechanisms are involved in these infections and an understanding of the pathogenesis is essential in understanding the diagnostic and clinical management aspects of the disease. Specialized investigations are often necessary for definitive diagnosis, although a presumptive diagnosis should often be suspected on the basis of the clinical features. Many of the chapters in this book are written by neurologists who are experts in basic science research of their topic in addition to active clinical practice in their specialty.

Although adenoviruses have been established for quite some time as one of the most pliable tools to study the molecular biology of mammalian cells, rapid progress continues to be made with this virus system. The adenoviral genome introduced into the nucleus of cells as a Trojan Horse, as it were, is now facili- tating investigators to uncover details of cellular mechanisms. In this volume twelve chapters have been collected that summarize important current research on different mechanisms in adenovirus- infected and -transformed cells. It has become increasingly apparent that some of these mechanisms do not only pertain to highly specialized strategies of the viral genome and its expres- sion or replication, but may simultaneously shed light on events indigenous to the cell. "Adenovirus DNA: The Viral Genome and its Expression" high- lights the first publication of the entire annotated sequence of 35. 937 nucleotide pairs of adenovirus type 2 DNA by the Cold Spring Harbor and Uppsala groups (chapter 1). Goran Akusjarvi, Ulf Pettersson (Uppsala University) and Rich Roberts (Cold Spring Harbor) present a survey on the structure and function of the adenovirus-2 genome (chapter 2). A considerable amount of in- formation has been collected on the biochemical mechanisms in- vol ved in adenov irus DNA repl ication in human cells. Al though highly specialized in the way of initiating DNA replication, adenov irus DNA repl ication represents probably one of the best studied systems in work on eukaryotic DNA replication.

The application of enzymes or whole cells (fermentatively active or resting; microbial, plant, or animal) to carry out selective transformations of commercial importance is the central theme of industrial biocatalysis. Traditionally, biocatalysis has been in the domain of the life scientist or biochemical engineer. However, recent advances in this field have enabled biocatalytic processes to compete head on with, and in some cases out perform, conventional chemical processing. Chemo-biocatalytic systems are being developed thereby combining the most attractive features of bio catalysts, namely high specificity, with those of chemical catalysts, such as high reactivities and wide substrate specificities. Hence, synthetic chemists and chemical engineers are now beginning to use biocatalysts as highly selective reagents in chemical synthesis and processing. This book is about biocatalysts and their past, present, and potential applications in the food, pharmaceutical, and chemical industries. The con cept of the book did not emanate from a meeting. Rather, it is a compila tion of selected examples where biocatalysis either has already made a significant impact in the aforementioned industries, or has the potential to make a substantial contribution. I have been fortunate to have assembled contributions from world-class researchers in the field of biocatalysis. Their timely contributions are sincerely appreciated."

This book covers the state-of-the-art research on molecular biology assays and molecular techniques enabled or enhanced by microfluidic platforms. Topics covered include microfluidic methods for cellular separations and single cell studies, droplet-based approaches to study protein expression and forensics, and microfluidic in situ hybridization for RNA analysis. Key molecular biology studies using model organisms are reviewed in detail. This is an ideal book for students and researchers in the microfluidics and molecular biology fields as well as engineers working in the biotechnology industry. This book also: Reviews exhaustively the latest techniques for single-cell genetic, epigenetic, metabolomic, and proteomic analysis Illustrates microfluidic approaches for inverse metabolic engineering, as well as analysis of circulating exosomes Broadens readers' understanding of microfluidics convection-based PCR technology, microfluidic RNA-seq, and microfluidics for robust mobile diagnostics