Staphylococcus aureus is now acknowledged as being the most important bacterial pathogen of humans. It usually produces localized disease but can be rapidly invasive, spreading through the tissues, invading bone, and seeding the bloodstream to produce a fulminant picture of septic shock, disseminated intravascular coagulation, and rapid death. Moreover, most strains of staph infections are becoming resistant to most antibiotics, thus posing a significant problem for hospitals and health care facilities. This book, a volume in the Infectious Agents and Pathogenesis series, presents chapters by the major researchers in the field.

This book contemplates the structure, dynamics and physics of virus particles: From the moment they come into existence by self-assembly from viral components produced in the infected cell, through their extracellular stage, until they recognise and infect a new host cell and cease to exist by losing their physical integrity to start a new infectious cycle. (Bio)physical techniques used to study the structure of virus particles and components, and some applications of structure-based studies of viruses are also contemplated. This book is aimed first at M.Sc. students, Ph.D. students and postdoctoral researchers with a university degree in biology, chemistry, physics or related scientific disciplines who share an interest or are actually working on viruses. We have aimed also at providing an updated account of many important concepts, techniques, studies and applications in structural and physical virology for established scientists working on viruses, irrespective of their physical, chemical or biological background and their field of expertise. We have not attempted to provide a collection of for-experts-only reviews focused mainly on the latest research in specific topics; we have not generally assumed that the reader knows all of the jargon and all but the most recent and advanced results in each topic dealt with in this book. In short, we have attempted to write a book basic enough to be useful to M.Sc and Ph.D. students, as well as advanced and current enough to be useful to senior scientists with an interest in Structural and/or Physical Virology.

1 The Genetics of Paramyxoviruses.- I. Introduction: The Genome Strategy of the Paramyxoviruses.- II. Genome Organization.- A. Genome Structure and function.- B. Coding Potential.- III. Genetic Interactions.- A. Absence of Genetic Recombination.- B. Complementation Analysis with Conditional Lethal Mutants.- C. Other Mutants.- IV. Analysis of Gene function.- A. Transport and Glycosylation of the G Glycoprotein of Respiratory Syncytial Virus.- B. Membrane Interactions of the F1 Polypeptide of SV5.- C. Gene-Specific Hypermutation in Measles Virus.- V Prospects.- VI. References.- 2 The Molecular Biology of the Paramyxovirus Genus.- I. Introduction.- A. History.- B. General Properties.- II. Virus Structure.- A. Morphology.- B. Virion Envelope and Envelope-Associated Proteins.- C. Internal Virion and Nonstructural Proteins.- III. Viral Replication.- A. Adsorption, Penetration, and Uncoating.- B. Molecular Organization of the Genome.- C. Transcription.- D. Genome Replication.- IV References.- 3 The Molecular Biology of the Morbilliviruses.- I. Introduction.- II. Genome Structure and Replication Strategy.- III. Genetic Relationships among the Morbilliviruses.- A. Nucleocapsid Protein Gene.- B. The Phosphoprotein Gene.- C. Matrix Protein Gene.- D. Fusion Protein Gene.- E. The Hemagglutinin Protein Gene.- F. The L Protein Gene.- IV. Function of the 5? and 3? Untranslated Regions.- V. Diagnosis Using Molecular Techniques.- VI. Morbillivirus Vaccines.- VII. Conclusions.- VIII. References.- 4 The Molecular Biology of Human Respiratory Syncytial Virus (RSV) of the Genus Pneumovirus.- I. Introduction.- II. Structures of the RSV Virion, RNAs, and Proteins.- A. Virion Structure.- B. Overview: Identification of Genomic RNA (vRNA), mRNAs, and Proteins.- C. Genetic Map of Strain A2.- D. Structures of the mRNAs.- E. Sequence Diversity among RSV Strains: Antigenic Subgroups.- F. Structures of the RSV Proteins.- III. RSV Replication.- A. Attachment, Penetration, and Growth Cycle.- B. vRNA Transcription.- C. vRNA Replication.- D. Virion Morphogenesis.- IV. Evolutionary Relationships.- A. RSV Antigenic Subgroups.- B. Relationships with Other Paramyxoviruses.- V. Conclusions.- VI. References.- 5 Evolutionary Relationships of Paramyxovirus Nucleocapsid-Associated Proteins.- I. Introduction.- A. Paramyxovirus Nucleocapsid Structure.- B. Functions of Nucleocapsid-Associated Proteins.- II. Sequence Analyses of Nucleocapsid Proteins.- A. NP Proteins.- B. L Proteins.- C. P Proteins.- III. Conclusions.- IV. References.- 6 The Nonstructural Proteins of Paramyxoviruses.- I. Introduction.- II. Paramyxovirus C Proteins.- A. Identification in Infected Cells.- B. The P and C Proteins are Encoded in Overlapping Reading Frames.- C. Multiple Initiation Codons on One mRNA.- D. Initiation Codon Consensus Sequences and the Scanning Hypothesis.- E. Subcellular Localization and Possible Function of Sendai Virus C Proteins.- F. When is a Nonstructural Protein a Structural Protein?.- G. Identification of C Proteins of Parinfluenza Virus 3, Measles Virus, and CDV.- III. Paramyxovirus Cysteine-Rich Proteins.- A. Identification of the Polypeptide and Its Gene in SV5.- B. Assignment of Coding Regions.- C. Strategy by Which P and V are Encoded.- D. Mechanism for the Addition of Extra Nucleotides to mRNAs.- E. Conservation of the Cysteine-Rich Region of Protein V in Paramyxoviruses.- F. Prediction of Cysteine-Rich Polypeptides and mRNAs with Extra Nucleotides in All Paramyxoviruses.- G. Identification of the Nonstructural Protein V and Its mRNAs in Other Paramyxoviruses.- H. Function of the Paramyxovirus Cysteine-Rich Protein V?.- IV. Paramyxovirus Small Hydrophobic (SH) Proteins.- A. Identification of the Polypeptide and Its Gene in SV5.- B. The SH Gene of Mumps Virus.- V Sendai Virus Nonstructural Polypeptide B: Intracellularly Phosphorylated Matrix Protein.- VI. Prospects.- VII. References.- 7 Paramyxovirus RNA Synthesis and P Gene Expression.- I. Paramyxovirus RNA Synthesis...

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.

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

Megaplasmids are extrachromosomal genetic elements in the size range of 100 kb and larger. They are found in physiologically and phylogenetically diverse groups of bacteria and archaea. By definition, megaplasmids are not essential for the viability of their hosts under all growth conditions, but paradoxically many megaplasmids carry the genetic information for the defining and characteristic traits of the organism in which they reside.

Microbial Megaplasmids reviews our knowledge of the extensively studied representatives, such as the catabolic plasmids of the pseudomonads, the rhizobial Sym plasmids, the Ti plasmids of the genus Agrobacterium and the giant enterobacterial virulence plasmids. It also presents snapshots of more recently discovered megaplasmids. The contribution of megaplasmids to the biology of their hosts is described, highlighting the interactions between megaplasmid and chromosomal genes.

Praise for the Series:
"This serial... is well known to virologists. It is a valuable aid in maintaining an overview of various facets of the rapidly expanding fields of virology... Timely, informative, and useful to student, teacher, and research scientist."
--American Scientist
"A mandatory purchase for all types of comprehensive libraries, both public and university, as well as for those interested in or doing research in the field of virology."
--Military Medicine

Key Features
* Among the topics covered are:
* Virus-induced immunopathology
* Filoviruses
* Molecular characterization of pestiviruses
* Transactivation of cellular genes by hepatitus B virus proteins
* Principles of molecular organization, expression, and evolution of closteroviruses
* Primate T lymphotropic oncoretroviruses
* Replication of positive-stranded RNA viruses of plants and animals

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.

The enormous advances in molecular biology that have been witnessed in . Not recent years have had major impacts on many areas of the biological sciences least of these has been in the field of clinical bacteriology and infectious disease . Molecular Bacteriology: Protocols and ClinicalApplications aims to provide the reader with an insight into the role that molecular methodology has to play in modern medical bacteriology. The introductory chapter ofMolecular Bacteriology: ProtocolsandCli- cal Applications offers a personal overview by a Consultant Medical Microbio- gist of the impact and future potential offered by molecular methods. The next six chapters comprise detailed protocols for a range of such methods . We believe that the use of these protocols should allow the reader to establish the various methods described in his or her own laboratory. In selecting the methods to be included in this section, we have concentrated on those that, arguably, have greatest current relevance to reference clinical bacteriology laboratories; we have deliberately chosen not to give detailed protocols for certain methods, such as multilocus enzyme electrophoresis that, in our opinion, remain the preserve of specialist la- ratories and that are not currently suited for general use. We feel that the methods included in this section will find increasing use in diagnostic laboratories and that it is important that the concepts, advantages, and limitations of each are th- oughly understood by a wide range of workers in the field .

The discovery of Epstein-Barr virus (EBV) by Epstein, Achong, and Barr, reported in 1964 (Lancet 1:702-703), was stimulated by Denis Burkitt's rec- nition of a novel African childhood lymphoma and his postulation that an infectious agent was involved in the tumor's etiology (Nature194:232-234, 1962). Since then, molecular and cellular biological and computational technologies have progressed by leaps and bounds. The advent of recombinant DNA technology opened the possibilities of genetic research more than most would have realized. Not only have the molecular tools permitted the analyses of viral mechanisms, but, importantly, they have formed the basis for discerning viral presence and, subsequently, viral involvement in an increasing number of diseases. Though in every field of science the search for further knowledge is likely to be a limitless phenomenon, the distinct goal in EBV research, namely, to gain sufficient insight into the viral-host interaction to be able to intercept the pathogenic process, is beginning to be realized. Epstein-Barr virus research has effectively entered the postgenomic era that began with the sequencing of the first strains, cloned in the mid to late 1980s.

"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.

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.

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.

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 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.

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 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.

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 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.

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. "

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.

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.

Medical mycology refers to the study of fungi that produce disease in humans and other animals, and of the diseases they produce, their ecology, and their epidemiology. This new edition has been fully revised to provide microbiologists with the latest information on fungal infections, covering the entire spectrum of different types of infection, and therapeutic modalities. Beginning with a general overview explaining morphology, taxonomy, and diagnosis, the following sections cover the different categories of fungal infection including superficial cutaneous mycoses, subcutaneous mycoses, systemic mycoses and opportunistic mycoses. A complete section is dedicated to pseudofungal infections. The highly illustrated text concludes with a detailed appendices section and each chapter features key references for further reading. Key points Fully revised, fourth edition providing latest information on the diagnosis and management of fungal infections Covers the entire spectrum of mycoses Highly illustrated with clinical photographs and figures Previous edition (9788188039780) published in 2009

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.