"Clostridium difficile" has been recognized as the cause of a broad spectrum of enteric disease ranging from mild antibiotic-associated diarrhea to pseudomembranous colitis. This volume gives new insights into the microbiology, diagnostics and epidemiology of "Clostridium difficile" and describes recent strategies in treatment of diseases caused by this agent. Main parts of the volume are devoted to "Clostridium difficile" toxins A and B which are the major virulence factors. The molecular biology, biochemistry, pharmacology and cell biology of these toxins which are the prototypes of a new family of large clostridial cytotoxins is described in great detail. "Clostridium difficile" toxins act as glucosyltransferases to inactivate small GTP-binding proteins of the Rho family which are involved in regulation of the actin cytoskeleton, cell adhesion and various signaling processes.

Prokaryotic Toxins - Antitoxins gives the first overview of an exciting and rapidly expanding research field. Toxin - antitoxin (TA) genes were discovered on plasmids 30 years ago. Since then it has become evident that TA genes are highly abundant in bacterial and archaeal chromosomes. TA genes code for an antitoxin that combine with and neutralize a cognate toxin. When activated, the toxins inhibit protein synthesis and cell growth and thereby induce dormancy and multidrug tolerance (persistence). Remarkably, in some species, the TA gene families have undergone dramatic expansions. For example, the highly persistent major human pathogen Mycobacterium tuberculosis has "100 TA loci. The large expansion of TA genes by some organisms is a biological mystery. However, recent observations indicate that TA genes contribute cumulatively to the persistence of bacteria. This medically important phenomenon may thus for the first time become experimentally tractable at the molecular level.

This first volume in a two-volume work enhances readers' understanding of antimicrobial resistance mechanisms in selected bacterial species that cause diseases in major food producing animals. It provides an overview of the current legislation and policies seeking to regulate the authorisation, manufacturing, distribution and use of veterinary antimicrobials in practice in a way that helps to contain the spread of antimicrobial resistance. The focus is put on Europe, without neglecting the global context. Moreover, attention is paid to various uses of antimicrobials in livestock, considering both their risks and benefits, from the distant past to the present. Growth promotion, prophylaxis, metaphylaxis, diagnostics and treatment are discussed not only with regard to food production and animal health, but also considering the One Health concept, which combines public and animal health with environmental aspects. A summary of various systems for monitoring the use of antimicrobials is provided, as well as an overview of the diseases that European veterinarians most often treat with antimicrobials. In closing, the book addresses the complexity of recent measures that are of key importance for antimicrobial stewardship, e.g. biosecurity, vaccination and other preventive tools including the newest technologies like smart farming. The complete two-volume work provides an extensive review of various aspects related to the use of antimicrobials in veterinary medicine, especially considering major food producing species, their most common infectious diseases and causative pathogens, and mainly focusing on the situation in Europe, without ignoring the global context. While Volume I discusses more general aspects of antibiotic use such as regulatory, laboratory and practical issues from different perspectives, Volume II more specifically discusses medical aspects and the use of antimicrobials in cattle, pigs, poultry and horses, as well as pharmacokinetics and pharmacodynamics, two of the most important factors determining the success of treatment. In both volumes, each chapter confronts the reader with open questions to stimulate further discussions and future research on the topics covered.

Microbial cell wall structures play a significant role in maintaining cells' shape, as protecting layers against harmful agents, in cell adhesion and in positive and negative biological activities with host cells. All prokaryotes, whether they are bacteria or archaea, rely on their surface polymers for these multiple functions. Their surfaces serve as the indispensable primary interfaces between the cell and its surroundings, often mediating or catalyzing important interactions.

"Prokaryotic Cell Wall Compounds" summarizes the current state of knowledge on the prokaryotic cell wall. Topics concerning bacterial and archaeal polymeric cell wall structures, biological activities, growth and inhibition, cell wall interactions and the applications of cell wall components, especially in the field of nanobiotechnology, are presented.

This book focuses on host-pathogen interactions at the metabolic level. It explores the metabolic requirements of the infectious agents, the microbial metabolic pathways that are dedicated to circumvent host immune mechanisms as well as the molecular mechanisms by which pathogens hijack host cell metabolism for their own benefit. Finally, it provides insights on the possible clinical and immunotherapeutic applications, as well as on the available experimental and analytical methods. The contributions break new ground in understanding the metabolic crosstalk between host and pathogen.

Mammalian reovirus had been the major focus for molecular understanding of the Reoviridae and has served as a model system for the other members of the family. Indeed, most of our initial understanding of molecular biology and processes involved in virus replication and pathogenesis for the members of the family was generated from reovirus studies. With this platform two other members of the family causing disease in human and/or animals have gained in prominence and the molecular interactions from a structural level through to host-virus interactions as well as the function of the structural and non-structural proteins in the virus life cycle has been investigated in detail.

This book reviews our current understanding of Reoviridae entry, disassembly/assembly and egress in addition to updating high resolution structures of virus proteins and capsids from three different genera of the family.

This book examines the current state of probiotic research and in particular focuses on the future potential of this important and exciting area. Probiotics and Prebiotics contains state-of-the-art commentaries on all aspects of the intestinal microflora and probiotics and provides an authoritative review of important aspects of probiotic research. Written by leading experts in the field, each chapter affords a critical insight to a particular topic, reviews current research, discusses future direction and stimulates discussion. Topics covered include the genomics of probiotic microorganisms, the developing technologies for analysis of gut microorganisms, evaluation and future potential of prebiotic substances, and the potential for disease prevention in the host by probiotic organisms. This book is an essential text for all microbiologists, health professionals, biotechnologists, pharmaceutical companies, and dairy and food scientists.

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.

It has been estimated that there are more microbial cells inhabiting the human body than there are eukaryotic cells of which it is made up. This normal microflora usually co-exists relatively peacefully with the host and does not cause infection. The mechanisms by which this co-existence is achieved are still not properly understood and the interaction between the normal microflora and the host is far from simple. For a variety of reasons, however, this interaction can be disturbed and often results in the microflora becoming pathogens. The study of the diseases then caused is important both in terms of treatment and in terms of contributing to our understanding of the mechanisms by which the normal microflora usually interacts with the host. This title brings together an international list of contributors, all of whom have active research interests in the normal microflora. Each of the chapters reviews current knowledge about a specific group or organism within the microflora and the diseases they can cause. Microflora of the skin, respiratory tract, oral cavity, gastrointestinal system and genital tract are all discussed and the impact of molecular methods on our understanding of the normal microflora is emphasised throughout the book. Medical microbiologists, dental specialists, infectious disease specialists, nutritionists and gastroenterologists will all find this book of immense interest and value, as will epidemiologists, dermatologists and general microbiologists.

This is the most comprehensive, up-to-date reference on this post-translational modification of proteins, which is intimately linked with DNA repair, maintenance of genomic stability, transcriptional regulation, cell death and a variety of other cellular phenomena as well as with a variety of pathophysiological conditions, including ischemia-reperfusion damage, Parkinson 's disease, Type I diabetes mellitus, hemorrhagic and septic shock and other inflammatory conditions. Richly illustrated, it offers 19 chapters written by international experts.

This book will assemble the views of many of the world's experts in the field of viruses and diabetes. It will look critically at some unanswered questions, in the field. Among these, How do viruses destroy or modify the pancreatic islet? Which viruses are involved? What is the role of virus-induced cytokines> Could vaccines prevent virus-induced diabetes? Until recent technological advances, progress in the understanding of the relationship between viruses and diabetes has been hampered. New technologies are helping shed new light on these mysteries. This will be the first comprehensive volume on this topic.

Although virology and immunology are now considered separate disciplines, history shows that these areas ofinvestigation always overlapped and one cannot really exist without the other. This trend has become particularly significant and fruitful in the past few years in the area of herpesvirus research. The genomes of the most important herpesviruses have been sequenced, a significant portion of their genes have been identified, and many secrets of regulation of gene expr- sion have been unraveled. Now this progress sets the stage for a true revolution in herpesvirus research: analysis of interactions between the host and the virus. Because herpesviruses can induce, suppress, and fool the immune system, the most productive herpesvirologists are also expert immunologists, and the current results ofthis interdisciplinary effort are truly remarkable. Because herpesviruses cause many important human diseases, the devel- ment of vaccines against these agents is a very significant goal. This effort is also very challenging because of the complexity of herpesviruses and the lack of sufficient information about immune responses. The remarkable ability of herpesviruses to escape immune responses is - other feature that brings immunology and virology together. Herpesviruses - code many proteins that interact with and down-regulate some key elements of the immune system. Thisproperty of herpesviruses represents amajor challenge in developing strategies against these viruses. On the positive side, these viral proteins also provide novel tools for analyzing specific immune reactions and molecular mechanisms.

One Health is an emerging concept that aims to bring together human, animal, and environmental health. Achieving harmonized approaches for disease detection and prevention is difficult because traditional boundaries of medical and veterinary practice must be crossed. In the 19th and early 20th centuries this was not the case then researchers like Louis Pasteur and Robert Koch and physicians like William Osler and Rudolph Virchow crossed the boundaries between animal and human health. More recently Calvin Schwabe revised the concept of One Medicine. This was critical for the advancement of the field of epidemiology, especially as applied to zoonotic diseases. The future of One Health is at a crossroads with a need to more clearly define its boundaries and demonstrate its benefits. Interestingly the greatest acceptance of One Health is seen in the developing world where it is having significant impacts on control of infectious diseases. "

Conceptually unsavoury, airway mucus is vital to homeostasis in the respiratory tract. In contrast, when abnormal, mucus contributes significantly to the pathophysiology of a number of severe bronchial diseases, including asthma, chronic bronchitis and cystic fibrosis. This volume provides wide ranging and in-depth coverage of the scientific and clinical aspects of airway mucus. It commences with introductory chapters which address the biochemical and molecular biological basis of airway mucus and continues with comprehensive coverage of the various physiological and rheological aspects of respiratory secretions. The clinical aspects of the topic are then considered, with chapters discussing the involvement of mucus secretions in bacterial infection and in hypersecretory diseases of the airway. The volume concludes with a discussion of the therapeutic aspects of the topic, both in terms of the possible approaches to the treatment of mucus hypersecretion and the interaction of these drugs with airway mucus. Written by leading experts in the field, each contribution provides a comprehensive review of its particular subject. Reflecting the latest advances in this important area of respiratory research, this volume will be of great interest to scientists and clinicians working in the field of airway secretions and related areas.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs). This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade. The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer's diseases, and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis and neuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

Scientists often look askance at their colleagues whose research appears too strongly focused on a single gene or gene product. We are supposed to be interested in the "big picture" and excessive zeal in pursuit of a single pixel might seem to border on an obsession that is likely to yield only details. However as this volume of Current Topics in Microbiology and Immunology demonstrates, this is certainly not the case for myc. Intense study of this en- matic proto-oncogene over the last twenty years has only broadened our view of its functions and led to insights into mechanisms relating to transcriptional regulation as well as to cell growth, proliferation, differentiation, apoptosis and organismal development. The myc gene originally came to light as a retroviral oncogene (v-myc) associated with a wide range of acute neoplasms. It was later shown to be a virally transduced cellular gene (c-myc) which is a member of family of on- genes (c-myc,N-myc,L-myc). These family members are themselves subject to a bewildering assortment of genetic rearrangements associated with many different types of tumors derived from many different types of cells. These rearrangements (including chromosomal translocation, viral integration, and gene ampli?cation) act to uncouple expression of the myc family genes from their normal physiological regulators. The chapter by LIU and LEVENS - scribes the key pathways leading to regulation of myc expression, showing that such regulation occurs at several different levels and through multiple mechanisms.

The discovery of wide-spread RNA-based regulation in bacteria has led to new evaluations of the importance of bacterial regulatory RNA in every aspect of bacterial physiology. In Bacteria Regulatory RNA: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study bacterial regulatory RNA. These include methods and techniques to identify regulatory RNAs, characterizing the function and expression of regulatory RNAs in bacterial cells, RNA structure prediction, and interactions between regulatory RNAs and proteins. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Bacteria Regulatory RNA: Methods and Protocols seeks to aid scientists in the further study of bacterial regulatory RNA.

The understanding how complement relates to glomerular diseases has evolved considerably during the last years. Substantial evidence has accumulated that explain how a defective or deregulated complement system results in kidney diseases. The combination and close interaction of basic research with clinical medicine has demonstrated an important role of complement effector and regulatory proteins in pathological settings of the kidney. A large panel of distinct human kidney diseases such as hemolytic uremic syndrome (HUS), membrano proliferative glomerulonephritis (MPGN), systemic lupus erythematosus (SLE) and in ischemic reperfusions injury and transplantation are caused by defective complement control. Genetic analyses have identified mutations in complement regulators that are associated with these diseases. Mutations have been identified in the fluid phase alternative pathway regulator Factor H and the membrane regulator Membrane Cofactor Protein MCP (CD46). The functional characterization of the mutant proteins allows to define the pathophysiological events on a molecular level. These new concepts and data on disease mechanisms already allowed to establish new diagnostic and novel promising therapeutic approaches for several human kidney diseases.

In eukaryotic cells, the nuclear genome and its transcriptional apparatus is separated from the site of protein synthesis by the nuclear envelope. Thus, a constant flow of proteins and nucleic acids has to cross the nuclear envelope in both directions. This transport in and out of the nucleus is mediated by nuclear pore complexes (NPCs) and occurs in an energy and signal-dependent manner. Thus, nucleocytoplasmic translocation of macro molecules across the nuclear envelope appears to be a highly specific and regulated process. Viruses that replicate their genome in the cell nucleus are therefore forced to develop efficient ways to deal with the intracellulZlr host cell transport machinery. Historically, investigation of Polyomavirus replication allowed identification ofsequences that mediate nuclear import, which led subsequently to our detailed understanding of the cellular factors that are involved in nuclear import. Transport ofmacromolecules in the opposite direction, however, is less well understood. The investigation of retroviral gene expression in recent years pro vided the first insights into the cellular mechanisms that regulate nuclear export. In particular, the detailed dissection of the function of the human immunodeficiency virus type I (HIV-I) Rev trans-activator protein identified CRMI, as a hona fide nuclear export receptor. CRM I appears to be involved in the nucleocytoplasmic translocation of the vast majority of viral and cellular proteins that have subsequently been found to contain a Rev-type leucine-rich nuclear export signal (NES)."

This volume provides an overview of the latency strategies developed during the estimated 200 Myears long coevolution of Alpha-, Beta- and Gammaherpesvirinae and their host species. The main emphasis is on herpesviruses infecting humans. However, relevant cases if herpesviruses infecting animals are covered as well. Special emphasis is drawn on results on molecular mechanisms regulating latent promoters of herpesvirus genomes and signals and molecular pathways resulting in reactivation of latent viral genomes. To balance the volume, epigenetic mechanisms (DNA methylation, histone modification, chromatin structure) involved in cell type specific expression of growth-transformation-associated Gammaherpesvirus genes will also be discussed at length)

Since penicillin and salvarsan were discovered, a number of new drugs to combat infectious diseases have been developed, but at the same time, the number of multi-resistant microorganism strains is increasing. Thus, the design of new and effective antibacterial, antiviral and antifungal agents will be a major challenge in the next years. This book reviews the current state-of-the-art in antimicrobial research and discusses new strategies for the design and discovery of novel therapies. Topics covered include the use of genetic engineering, genome mining, manipulation of gene clusters, X-ray and neutron scattering as well as the antimicrobial effects of essential oils, antimicrobial agents of plant origin, beta-lactam antibiotics, antimicrobial peptides, and cell-wall-affecting antifungal antibiotics.

The OHOLO conferences are sponsored by the Israel Institute for Biological Research and take their name from the site of the ?rst meeting on the shores of Lake Kinnereth. The purpose of these meetings is, as it was at their inception over 50 years ago, "to foster interdisciplinary communication between scientists in Israel, and to provide added stimulus by the participation of invited scientists from abroad". The core of the organizers of the OHOLO conferences are scientists from the Israel Institute for Biological Research. From time to time a particular OHOLO conference cooperates with an international scienti?c organization. The present 46th OHOLO Conference marks the resumption of the OHOLO tradition after 8 years of interruption caused by events beyond our control. It is my belief that our uncomp- mising commitment to excellence in research and development in the various areas of science in Israel is essential to our survival in this troubled region. The OHOLO conference tradition is a re?ection of this conviction. The present 46th OHOLO Conference entitled: The Challenge of Highly Pathogenic Microorganisms - Mechanisms of Virulence and Novel Medical Countermeasures intends to address the unique virulence features and ho- pathogen interactions of microorganisms constituting emerging biothreat with emphasis on Y. pestis, B. anthracis, F. tularensis and Orthopox viruses. Accordingly we selected classical microbiological as well as genomic, proteomic & transcr- tomic approaches towards developments of novel prophylactic and post-exposure treatment, as well as updated strategies of diagnostics and bioforensics.

The books in this acclaimed series are the most detailed, up-to-date accounts of the field available. Volume 3 explores the oncogenic potential shared by retroviruses of different species, the widespread presence of retrovirues in nature, and the role of retroviruses in normal development and pathogenesis.

Epigenetic modification of cellular genomes is a fascinating means of regulating tissue- and cell type-specific gene expression in all developmental stages of the life of an organism. Carefully orchestrated processes, such as DNA methylation and a plenitude of specific histone modifications secure the faithful transmission of gene expression patterns to progeny cells. Upon chronic infection, the epigenetic cellular balance can become disrupted and, in the long run, through the epigenetic reprogramming of host cell genomes, contribute to the malignant conversion of formerly healthy cells, in many cases preceded by the establishment of an epigenetic field of cancerization. The present volume undertakes to highlight the interactions of infectious pathogens and their effector molecules with the epigenetic regulatory machinery of the cell. Clearly, the recent take-off of epigenetics research did not leave Research on Infectious Diseases and Infection-Associated Cancer untouched. This resulted in a great many of clinically relevant data on understanding the molecular mechanisms of chronic infectious disease. Infectious pathogen- and disease-specific epigenetic alterations are already being used for the early detection of malignant disease and for the prediction of chemotherapy resistance or response to treatment.