This book describes antibiotic resistance amongst pathogenic bacteria. It starts with an overview of the erosion of the efficacy of antibiotics by resistance and the decrease in the rate of replacement of redundant compounds. The origins of antibiotic resistance are then described. It is proposed that there is a large bacterial resistome which is a collection of all resistance genes and their precursors in both pathogenic and non-pathogenic bacteria. Ongoing resistance surveillance programs are also discussed, together with the perspective of a clinical microbiologist. The book then turns to specific themes such as the most serious area of resistance in pathogens, namely in Gram-negative organisms. The role of combinations of antibiotics in combating resistance emergence is discussed, particularly in the tuberculosis field, and then the importance of non-multiplying and persistent bacteria which are phenotypically resistant to antibiotics and prolong the duration of therapy of antibiotics which leads to poor compliance and resistance emergence. The role of anti-microbial compounds in textiles is covered, with its potential to exacerbate the spread of resistance. Then, efflux pumps are discussed. The final chapter describes the compounds which are in late stage clinical development, illustrating the paucity of the antibiotic pipeline, especially for Gram-negative bacteria.

Coronaviruses were recognized as a group of enveloped, RNA viruses in 1968 and accepted by the International Committee on the Taxonomy of Viruses as a separate family, the Coronaviridae, in 1975. By 1978, it had become evident that the coronavirus genomic RNA was infectious (i. e. , positive strand), and by 1983, at least the framework of the coronavirus replication strategy had been per ceived. Subsequently, with the application of recombinant DNA techniques, there have been remarkable advances in our understanding of the molecular biology of coronaviruses, and a mass of structural data concerning coronavirus genomes, mRNAs, and pro teins now exists. More recently, attention has been focused on the role of essential and accessory gene products in the coronavirus replication cyde and a molecular analysis of the structure-function relation ships of coronavirus proteins. Nevertheless, there are still large gaps in our knowledge, for instance, in areas such as the genesis of coronavirus subgenomic mRNAs or the function of the coronavirus RNA-dependent RNA polymerase. The diseases caused by coronaviruses have been known for much longer than the agents themselves. Possibly the first coronavirus-related disease to be recorded was feline infectious peritonitis, as early as 1912. The diseases associ ated with infectious bronchitis virus, transmissible gastroenteritis virus, and murine hepatitis virus were all well known before 1950.

The recent developments in modern vaccinology are mainly based on: (i) cloning of microbial genes into recombinant vectors containing genetic information for expression of desired neutralizing immunogens; (ii) alternatives of attenuated vectors with deleted genes permitting the insertion of several foreign genes expressing antigens exposed to the host immune system during the abortive replication of such vectors; (iii) combined vaccines with the aim to protect against many diseases with a limited number of administrations; (iv) evidence demonstrating the ability of animals to respond serologically to DNA injections considered as a potential method of vaccination; (v) the possibility to manipulate the immune system with new and improved immunomodulators enhancing the immune response; and (vi) new microcarrier systems for particular immunogens or immunomodulators delivery, either in a single dose or sustained release, and presentation to the immune system for a relevant response. New vaccines being developed are mainly based on viral, bacterial or other vectors modified with genetic engineering technology, to possess and express desired antigens for vaccination against single or multiple infections. Existing combined vaccines like diphtheria, tetanus, pertussis (DTP) are also experimented with new additional components like recombinant hepatitis B virus surface antigen, inactivated poliovirus, and Haemophilus inJluenzae type b immunogens, in order to produce multivalent vaccines. Such types of vaccines permitting the reduction of multiple medical visits is of particular interest to pediatric immuni zation programs, and would benefit especially the developing countries assuring better vaccine compliance with immunization schedules.

The intestinal protozoan Giardia was first described over 300 years ago in 1681 by Leeuwenhoek, from his own stools. In his description of Giardia, he noted the size, movement, and morphology of the organism, and associated its presence with the diarrheic nature of his stools and his dietary habits. This truly remarkable account contains the first description of Giardia in morphologic, pathogenic, and epidemiologic terms. Our knowledge of the organisms in the genus Giardia has advanced tremendously in the past two decades. With the advent of new tech nologies, including techniques in electron microscopy, biochemistry, immunochemistry, tissue culture, and physiology, a tidal wave of information has appeared on the organization and function of this parasitic protozoan and its interaction with its host. The purpose of this book is to celebrate the tricentennial discovery of Giardia by Leeuwenhoek by presenting the above-mentioned advances in our knowledge of Giardia and giardiasis. In the first section of this book, the dominant theme is the biology of the organism and the correlation of structure-function relationships."

Methane and its oxidation product, methanol, have occupied an important position in the chemical industry for many years: the former as a feedstock, the latter as a primary chemical from which many products are produced. More recently, the role played by methane as a potent "greenhouse" gas has aroused considerable attention from environmentalists and clima tologists alike. This role for C compounds has, of course, been quite 1 incidental to the myriad of microorganisms on this planet that have adapted their life-styles to take advantage of these readily available am bient sources. Methane, a renewable energy source that will always be with us, is actually a difficult molecule to activate; so any microorganism that can effect this may point the way to catalytic chemists looking for con trollable methane oxidation. Methanol, formed as a breakdown product of plant material, is also ubiquitous and has also encouraged the growth of prokaryotes and eukaryotes alike. In an attempt to give a balanced view of how microorganisms have been able to exploit these simple carbon sources, we have asked a number ofleading scientists (modesty forbids our own inclusion here) to contribute chapters on their specialist areas of the subject.

Vaccination is one of the most efficient and cost effective methods of promoting human health and has been in clinical use for at least 200 years. Nevertheless, infectious diseases continue to constitute a constant threat to the well being of humanity. Common pathogens, once believed to be under control, acquire increased virulence and resistance to drugs, while exotic microorganisms emerged from hidden reservoirs to cause yet incurable diseases in humans. These changes, together with epidemic outbreaks related to political and socio-economic instabilities, increase the needs for the development of new, advanced vaccines. In this volume, devoted to the proceedings of the 39th OHOLO Conference, we present some of the recent strategies for the design and production of novel vaccines. The advent of recombinant DNA technology has stimulated the production of several subunit vaccines. In spite of the obvious advantages to this approach, the limited immuno genicity of many subunit candidates has hindered their development. Strategies to enhance the immunogenicity of subunit vaccines is therefore critical. Several approaches toward this goal, including design of novel adjuvants and delivery systems as well as design of advantageous carriers, are presented here. Among the carriers evaluated here are polypep tides (flagellin, HBV core antigen, J3-galactosidase), attenuated virions (Vaccinia, Sindbis), and nonpathogenic licensed bacteria (Salmonella)."

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.

Henipaviruses form a new genus of emerging paramyxoviruses that are the deadliest human pathogens within the Paramyxoviridae family. This volume deals with the many facets of henipavirus biology, and covers our current understanding regarding the ecology, molecular virology, and pathogenesis of henipavirus infections. It is an international effort written by a multidisciplinary panel of experts at the front lines of research into this lethal emerging group of paramyxoviruses. The first section introduces the epidemiology and ecology of Nipah and Hendra viruses in their respective endemic areas, including a first-hand account of the discovery of Nipah virus during its initial outbreak in Malaysia; the next section documents the molecular virology of henipaviruses, and the substantial advances made towards understanding the unique features of henipavirus entry and tropism; and this is followed by accounts of the clinical and pathologic features of henipavirus infections in their human and naturally infected animal hosts. The next sections on pathogenesis provide a comprehensive reference on how henipaviruses counteract the innate immune system, and the relevant pathogenic features in animal challenge models developed to test potential therapeutic strategies. The final sections describe our current and future capabilities for diagnosis and control, including an account of potentially effective immunization strategies that are currently being tested. This book will not only serve as a useful reference for the henipavirus field; it will be useful to basic and animal virologists, ecologists, epidemiologists, physicians, and others interested in emerging infectious viral diseases, as it showcases the multidisciplinary efforts required to understand the genesis, spread and hopefully, control, of a group of lethal emerging zoonotic pathogens.

Over the last few years, bacterial adhesion has become a more and more important and active scientific area, but the field lacks communication and scientific exchange between medical and microbiology researchers who work with the relevant biological systems, and biochemists, structural biologists and physicists, who know and understand the physical methods best suited to investigate the phenomenon at the molecular level. The field consequently would benefit from a cross-disciplinary conference enabling such communication. This book tries to bridge the gap between the disciplines.

Experts in microbiology and autoimmunity examine the association between microorganisms and the development of specific categories of autoimmune diseases. The opening chapters explore the bacterial induction of diseases considered autoimmune in nature. Subsequent chapters describe the role of viruses in the induction of these diseases and of diseases with an autoimmune component. Specific topics include: the role of streptococcal infection in rheumatic fever and the role of Klebsiella in the development of ankylosing spondylitis.

It is now just 20 years since Gomatos and his co-workers at the Rocke feller University showed that the nucleic acid in reovirus particles is double-stranded RNA (dsRNA). This discovery created great excitement, for dsRNA was at that time under intense investigation as the replicative form of viral genomes consisting of single-stranded RNA. An equally interesting and important finding followed soon after: it was found that the reovirus genome consists, not of a single nucleic acid molecule, but of 10 discrete "segments," each with its specific sequence content and each transcribed into its own messenger RNA. It is clear now that these segments are genes. Not surprisingly, the availability of a viral genome 10 unlinked genes has permitted some unique lines of in consisting of vestigation in molecular biology. Mammalian and avian reoviruses proved to be but the first of several viruses recognized as sharing Similarity in size and morphology and ge nomes consisting of 10, II, or 12 separate genes. These viruses are dis tributed throughout living organisms; among the natural hosts of mem bers of this virus family are vertebrates, Insects, and plants. Members of the Reoviridae family differ widely in the virulence that they exhibit toward their hosts . . For example, the first discovered mam malian reovirus literally is, as the name signifies, a "respiratory enteric orphan" virus, that is, a virus unassociated with disease."

No other area of biology has grown as fast and become as relevant over the last decade as virology. It is with no little amount of amaze ment, that the more we learn about fundamental biological questions and mechanisms of diseases, the more obvious it becomes that viruses perme ate all facets of our lives. While on one hand viruses are known to cause acute and chronic, mild and fatal, focal and generalized diseases, on the other hand, they are used as tools for gaining an understanding of the structure and function of higher organisms, and as vehicles for carrying protective or curative therapies. The wide scope of approaches to different biological and medical virological questions was well rep resented by the speakers that participated in this year's Symposium. While the epidemic by the human immunodeficiency virus type 1 continues to spread without hope for much relief in sight, intriguing questions and answers in the area of diagnostics, clinical manifestations and therapeutical approaches to viral infections are unveiled daily. Let us hope, that with the increasing awareness by our society of the role played by viruses, not only as causative agents of diseases, but also as models for better understanding basic biological principles, more efforts and resources are placed into their study. Luis M. de la Maza Irvine, California Ellena M."

Vector transmission of pathogens affecting human, animal, and plant health continues to plague mankind both in industrialized and Third World coun tries. The diseases caused by these pathogens cost billions of dollars an nually in medical expenses and lost productivity. Some cause widespread of food-and fiber-producing plants and animals, whereas others destruction present direct and immediate threats to human life and further development in Third World countries. During the past 15 years or so, we have witnessed an explosive increase in interest in how vectors acquire, carry, and subsequently inoculate dis ease agents to human, animal, and plant hosts. This interest transcends the boundaries of anyone discipline and involves researchers from such varied fields as human and veterinary medicine, entomology, plant pa thology, virology, physiology, microbiology, parasitology, biochemistry, molecular biology, genetic engineering, ultrastructure, biophysics, bio systematics, biogeography, ecology, behavioral sciences, and others. Ac companying and perhaps generating this renewed interest is the realization that fundamental knowledge of pathogen-vector-host interrelationships is a first and necessary step in our quest for efficient, safe methods of disease control."

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.

TwentyyearshavegonebysinceJackSokatch?rstpublishedhisoutsta- ingTheBiologyofPseudomonasbackin1986.Thiswasfollowedbytwobooks published by the ASM that contained the presentations of the Pseudomonas meetings held in Chicago in 1989 and Trieste in 1991. The earlier volume of these two was edited by Simon Silver, Al Chakrabarty, Barbara Iglewski, and Sam Kaplan, and the later one by Enrica Galli, Simon Silver, and Bernard Witholt. The time was ripe for a series of books on Pseudomonas because of its importance in human and plant pathogenesis, bio?lms, soil and rhizosphere colonization, etc. Efforts were devoted to produce the ?rst three volumes of the series on the biology of Pseudomonas after a meeting with Kluwer staff members in August 2002 during the XI IUMS conference in Paris (France). In less than a year a group of outstanding scientists in the ?eld, after devoting much of their valuable time, managed to complete their chapters for the three volumes of the series. To ensure the high standard of each chapter, renowned scientists participated in the reviewing process. The three books collected part of the "explosion" of new vital information on the genus Pseudomonas.

This book is a compilation of the research which was presented during the NATO-Advanced Research Workshop (ARW) entitled "Advances in Bacterial Paracrystalline Surface Layers" held in London, Ontario, Canada during September 27 to 30, 1992. The organizing committee consisted of the two Workshop directors, S. F. Kaval and T. J. Beveridge, and H. Konig, U. B. Sleytr and T. J. Trust; their summary statements about the significance and success of the NATO-ARWare in Chapter 37 of this book. This was the third international workshop on bacterial S-layers and it demonstrated unequivocally how rapidly research is progressing. The Workshop was made possible by financial support from the North Atlantic Treaty Organization (NATO), the Medical Research Council of Canada (MRC), the Natural Seiences and Engineering Research Council of Canada (NSERC), and the Canadian Bacterial Diseases Network (CBDN) which is a Canadian National Centre of Excellence (NCE). We are very grateful for the support from all of these agencies since their financial aid made it possible to bring to London, Canada a truly international group of S-layer experts. We encouraged the attendance and participation of graduate fellows and research associates, and their presentations students, postdoctoral was an intense three constitute the "Poster" section of this book. The NATO-ARW day workshop held at a delightful secluded location (Spencer Hall) so that the delegates had both formal and informal occasions to interact and evolve new ideas."

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.

The world needs clean and renewable energy and hydrogen represents an almost ideal resource. Hydrogen is the simplest and most abundant molecule in the universe, yet one that is a challenge to produce from renewable resources. Biohydrogen, or hydrogen produced from renewable resources such as water or organic wastes by biological means, is a goal worthy of increased global attention and resources. The purpose of BioHydrogen '97 was to bring together leaders in the biological p- duction of hydrogen from the United States, Japan, Europe, and elsewhere to exchange scientific and technical information and catalyze further cooperative programs. Parti- pants came from at least different countries representing academia, industry, and g- ernment. Especially important participants were young research scientists and engineers: the next generation of contributors. The conference consisted of plenary presentations, topical sessions, posters, and mini-workshop discussions on key areas of biohydrogen. It was designed to maximize - formation exchange, personal interaction among participants, and formulate new inter- tional initiatives. BioHydrogen '97 was an outgrowth of an international workshop convened by the Research Institute of Innovative Technology for the Earth (RITE) and was held in Tokyo, Japan, November 24-25, 1994. The RITE workshop was highly successful but largely l- ited to traditional biochemical and biological studies and not engineering research topics.

The time seems ripe for a critical compendium of that segment of the biological universe we call viruses. Virology, as a science, having passed only recently through its descriptive phase of naming and num bering, has probably reached that stage at which relatively few new-truly new-viruses will be discovered. Triggered by the intellectual probes and techniques of molecular biology, genetics, bio chemical cytology, and high resolution microscopy and spec troscopy, the field has experienced a genuine information explosion. Few serious attempts have been made to chronicle these events. This comprehensive series, which will comprise some 6000 pages in a total of about 18 volumes, represents a commitment by a large group of active investigators to analyze, digest, and expostulate on the great mass of data relating to viruses, much of which is now amorphous and disjointed, and scattered throughout a wide literature. In this way, we hope to place the entire field in perspective, and to develop an invalua ble reference and sourcebook for researchers and students at all levels. This series is designed as a continuum that can be entered anywhere, but which also provides a logical progression of developing facts and integrated concepts.

The papers contained in this book were presented at a NATO Advanced Research Workshop (ARW) held at Cape Sounion, Athens, Greece, 19-24 May, 1991. The twenty-eight more comprehensive papers represent the key subjects of the ARW covered by invited speakers. The thirty-four short papers pre sented in a research format are contributions of those invited to participate in the ARW. There was a total of 70 participants from 21 countries. The objectives of the ARW were as follows: to review current knowledge of biological control of plant diseases and plant parasitic nematodes, with emphasis on mechanisms at the molecular, cellular, organismal, and ecosystem level; to examine and expand on current concepts and synthesize new concepts; to identify and prioritize limitations in the use of biological control for plant diseases and nematodes and the scientific research needed to overcome these limitations; and to develop strategies for biological control through management of resident agents or introduction of natural or modified agents."

Biotechnology is a word that was originally coined to describe the new processes which could be derived from our ability to manipulate, in vitro, the genetic material common to all organisms. I t has now become a generic term encompassing all "applications" of living systems, including the more traditional fermentation and agricultural industries. Recombinant DNA technology has opened up new opportunities for the exploitation of microorganisms and animal and plant cells as producers or modifiers of chemical and biological products. This series of handbooks deals exclusively with microorganisms which are at the forefront of the new technologies and brings together in each of its volumes the background information necessary to appreciate the historical development of the organisms making up a particular genus, the degree to which molecular biology has opened up new opportunities, and the place they occupy in today's biotechnology industry. Our aim was to make this primarily a practical approach, with emphasis on methodology, combining for the first time information which has largely been spread across a wide literature base or only touched upon briefly in review articles. Each handbook should provide the reader with a source text, from which the importance of the genus to his or her work can be identified, and a practical guide to the handling and exploitation of the organisms included.

In this translation of the Italian second edition, the authors provide a comprehensive account of the current knowledge on antibiotics. They concisely describe how various scientific disciplines are involved in antibiotics research, development, and use. Their work also discusses the industrial and clinical development of new antibiotics, as well as the questions and controversies related to the function of antibiotics in nature. Antibiotics is richly illustrated with clear chemical structures, drawings, diagrams, and synoptical tables.

The literature in microbial ecology is growing rapidly. Journals in many countries dealing with microbiology, ecology, environmental sciences, and environmental technology are publishing an ever-increasing number of papers, and these reports are providing microbial ecologists with a wealth of information. This body of data is now so large and the research is published in so many journals and mono graphs that maintaining an overview of the development of the field grows more difficult. The role of Advances in Microbial Ecology thus becomes more obvious with time. The articles in the present volume encompass an array of topics appropriate to the development of the discipline of microbial ecology. Both terrestrial and aquatic ecosystems are subjects of attention, and a variety of microbiological groups come under review. Furthermore, methodological problems and ap proaches are not overlooked. The ecology of protozoa, constraints on their populations, and their role in nutrient cycling and energy flow are considered by J. D. Stout. A unique micro environment is discussed by B. Norkrans, the surface microlayer of aquatic eco systems, and Dr. Norkrans presents information on a field that has blossomed in the last few years. The subject of the review by H. S. Lowendorf is the genus Rhizobium, a group of bacteria whose importance has grown as the cost of fuel for production of nitrogen fertilizers and ultimately for protein production has increased.