Infectious fungal diseases continue to take their toll in terms of human suffering and enormous economic losses. Invasive infections by opportunistic fungal pathogens are a major cause of morbidity and mortality in immuno-compromised individuals. At the same time, plant pathogenic fungi have devastating effects on crop production and human health. New strategies for antifungal control are required to meet the challenges posed by these agents, and such approaches can only be developed through the identification of novel biochemical and molecular targets. However, in contrast to bacterial pathogens, fungi display a wealth of lifestyles and modes of infection. This diversity makes it extremely difficult to identify individual, evolutionarily conserved virulence determinants and represents a major stumbling block in the search for common antifungal targets. In order to activate the infection programme, all fungal pathogens must undergo appropriate developmental transitions that involve cellular differentiation and the introduction of a new morphogenetic programme. How growth, cell cycle progression and morphogenesis are co-ordinately regulated during development has been an active area of research in fungal model systems such as budding and fission yeast. By contrast, we have only limited knowledge of how these developmental processes shape fungal pathogenicity, or of the role of the cell cycle and morphogenesis regulators as true virulence factors. This book combines state-of-the-art expertise from diverse pathogen model systems to update our current understanding of the regulation of fungal morphogenesis as a key determinant of pathogenicity in fungi.

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This Brief describes the concept and realization of gene therapy for HIV from the unique historic perspective and insight of two pioneers of the clinical applications of stem cell gene therapy for HIV. Gerhard Bauer applied ribozyme-anti-HIV and other vectors to manufacture clinical grade, HIV-resistant hematopoietic stem cells for the first patients that received stem cell gene therapy for HIV, including the first child in the world and the first fully marrow-ablated HIV infected patient. Joseph Anderson developed the most recent and most potent combination anti-HIV lentiviral vectors and pluripotent stem cell applications for HIV gene therapy and tested these in the appropriate in vitro and vivo models, paving the way for novel HIV gene therapy approaches to possibly cure patients. In Gene Therapy for HIV, Bauer and Anderson discuss the unique aspects of this therapy, including its limitations and proper safety precautions and outline a path for a possible functional cure for HIV using stem cell gene therapy based on a cure already achieved with a bone marrow stem cell transplantation performed in Germany using donor stem cells with a naturally arising CCR5 mutation. In addition, the Brief provides a thorough and methodical explanation of the basics of gene therapy, gene therapy vector development, in vitro and in vivo models for HIV gene therapy and clinical applications of HIV gene therapy, including Good Manufacturing Practices.

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.

Microbial endocrinology represents a newly emerging interdisciplinary field that is formed by the intersection of the fields of neurobiology and microbiology. This book will introduce a new perspective to the current understanding not only of the factors that mediate the ability of microbes to cause disease, but also to the mechanisms that maintain normal homeostasis. The discovery that microbes can directly respond to neuroendocrine hormones, as evidenced by increased growth and production of virulence-associated factors, provides for a new framework with which to investigate how microorganisms interface not only with vertebrates, but also with invertebrates and even plants. The reader will learn that the neuroendocrine hormones that one most commonly associates with mammals are actually found throughout the plant, insect and microbial communities to an extent that will undoubtedly surprise many, and most importantly, how interactions between microbes and neuroendocrine hormones can influence the pathophysiology of infectious disease.

The objective of this" CTMI" volume is to provide readers with a foundation for understanding what ADARs are and how they act to affect gene expression and function. It is becoming increasingly apparent that ADARs may possess roles not only as enzymes that deaminate adenosine to produce inosine in RNA substrates with double-stranded character, but also as proteins independent of their catalytic property. Because A-to-I editing may affect base-pairing and RNA structure, processes including translation, splicing, RNA replication, and miR and siRNA silencing may be affected. Future studies of ADARs no doubt will provide us with additional surprises and new insights into the modulation of biological processes by the ADAR family of proteins. "

Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.

Dirk Haller und Gabriele Hörmannsperger geben einen Überblick über die zentrale Rolle des Darms und seiner Bewohner für die Gesundheit und vermitteln zusätzlich einen ersten Eindruck von den komplexen und dynamischen Interaktionen zwischen D+armbakterien und Wirt. Denn Forschungsergebnisse der letzten Jahre weisen darauf hin, dass die lange unbeachteten Darmbakterien (intestinale Mikrobiota) eine unerwartet zentrale Rolle für die Aufrechterhaltung der Gesundheit einnehmen. Die Forschung beschäftigt sich aktuell intensiv damit, die Grundlagen für ein funktionierendes und gesundheitsförderndes mikrobielles Ökosystem zu identifizieren. Dieses Wissen kann zukünftig für die Entwicklung gezielter Maßnahmen zur Prävention und Therapie Mikrobiota-assoziierter Erkrankungen eingesetzt werden.

Clinical Mycology offers a comprehensive review of this discipline. Organized by types of fungi, this volume covers microbiologic, epidemiologic and demographic aspects of fungal infections as well as diagnostic, clinical, therapeutic, and preventive approaches. Special patient populations are also detailed.

This book gives a very timely account of recent - partly unpublished - research on the development of gram-positive bacteria as vaccine delivery vehicles for mucosal immunization. The practical and theoretical considerations are discussed and the basic concepts behind the different approaches are compared by giving specific examples of the use of different non-pathogenic bacteria as vaccine vehicles. Thus, a common framework of concepts for a new generation of mucosal vaccines is provided.

Since the subject of arenaviruses was visited by "Current " "Topics in Microbiology and Immunology" 14 years ago, enormous advances have been made in this area. The receptor for several arenaviruses, alpha-dystroglycan, was identified, the replication strategy of these viruses was decoded, and application of a reverse genetics system for studying viral gene function and viral biology is well underway.
In addition to reviewing these advances, Volume I includes discussion of arenaviral molecular phylogeny, reservoirs in rodents and clinical diseases caused by both new world and old world arenaviruses.

A comprehensive review of all known immune mechanisms for medically important fungal pathogens from the organ perspectives of the human body. This authoritative guide is organized by organ system, as one particular fungus can have several different effects.

This book is about mechanisms of intracellular parasitism of Legionella, Listeria and Mycobacterium. The presented data illustrate the hypothesis that one of the ways by which intracellularly multiplying bacteria influence the bactericidal response of phagocytes is by altering signaling cascades in eukaryotes. To achieve this goal bacteria are capable to produce enzymes and other biologically active compounds which misdirect signaling pathways for the benefit of the parasites. The book is composed of two main parts. The first provides general information on signaling cascades in eukaryotic cells. Analysis of Legionella, Listeria and Mycobacterium products possessing regulatory activity toward metabolism of host cells, essentially by affecting signal transduction in eukaryotes, is performed in the second section.

Parasitic diseases still affect millions of people every year, especially in the tropics, causing considerable morbidity or death. Such infections within livestock are probably an even bigger problem, leading to poorer productivity, condemna tion of infected meat and considerable economic loss. Para sitological research has, however, helped the situation in some cases and the development of novel drugs, vaccines and diagnostics has improved our chances of controlling these diseases. Research into parasitic infections is, therefore, often goal orientated. However, the study of parasites and host/parasite relationships still remains one of the most exciting and in teresting aspects of biology. Scientists, from undergraduate students to research professors, frequently ponder over how endoparasitic organisms can survive within the most alien of environments - inside another organism. The nutritional, reproductive and survival strategies which have evolved within each group of parasites have allowed the development of highly specific host-parasite relationships and allow the successful transmission of the parasite from one host to an other. A considerable amount of research is therefore direc ted at improving our understanding of various aspects of parasite biology."

As yet, flow cytometry is not used so widely in microbiology as in some other disciplines. This volume presents contributions flow cytometry to study a from research microbiologists who use diverse set of problems. It illustrates the power of the technique, and may persuade others of its usefulness. Most of the con tributors gathered in Cardiff on 23 October 1991, at a meeting organized for the Royal Microscopical Society by Dr. Richard Allman, but the content of their chapters is not limited by the discourse of that meeting, and for balance other experts were invited to write for this book. Flow Cytometry in Microbiology thus represents the first collection of articles specifically devoted to the applications of a technique which promises so much to those investigating the microbial world. Cardiff, 1992 David Lloyd Contents List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Flow Cytometry: A Technique Waiting for Microbiologists David Lloyd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 The Physical and Biological Basis for Flow Cytometry of Escherichia coli Erik Boye and Harald B. Steen . . . . . . . . . . . . . . . . . . . . . . 11 3 Flow Cytometric Analysis of Heterogeneous Bacterial Populations Richard Allman, Richard Manchee and David Lloyd. . . . 27 4 On the Determination of the Size of Microbial Cells Using Flow Cytometry Hazel M. Davey, Chris L. Davey and Douglas B. Kell . . 49 5 Uses of Membrane Potential Sensitive Dyes with Bacteria David Mason, Richard Allman and David Lloyd . . . . . . .

Living in biofilms is the common way of life of microorganisms, transiently immobilized in their matrix of extracellular polymeric substances (EPS), interacting in many ways and using the matrix as an external digestion and protection system. This is how they have organized their life in the environment, in the medical context and in technical systems - and has helped make them the oldest, most successful and ubiquitous form of life. In this book, hot spots in current biofilm research are presented in critical and sometimes provocative chapters. This serves a twofold purpose: to provide an overview and to inspire further discussions. Above all, the book seeks to stimulate lateral thinking.

1 Fleas are wingless insects with a laterally compressed body of about 1.5-4 mm length. Like all insects they possess six legs and three body segments. Taxonomically they belong to the order Siphonaptera (Eckert et al. 2000) (Table 1). This family contains several species and subspecies. Fleas represent one of the most important ectoparasites (Mehl- horn 2000; Mehlhorn et al. 2001b). At the moment there are more than 2000 described species and subspecies throughout the world (Borror et al. 1981). These species belong to the families Pulicidae, including Pulex spp., Ctenocephalides spp., Spilopsyllus spp. and Archaeopsyllus spp., or the familia Ceratophyllidae with the genuses Ceratophyllus or Nosopsyllus to mention only some of the most important veterinary and human representatives. Fleas have a history of about 60 million years and were already found on prehistoric mammals. While becoming parasitic the original exterior of the two-wing insects, also designated as the order Diptera, has changed by losing the wings in the adults, whereas the larval form still has similarity with the larva of the order Diptera (Strenger 1973). About 95% of the -2000 different flea species parasitize on mammals, 5% live on birds. Table 1. Taxonomy of fleas Systematic Taxonomy Phylum Arthropoda Tracheata (=Antennata) Subphylum Classis Insecta (Hexapoda) Ordo Siphonapterida Familia Pulicidae Familia CeratophyUidae Genus Ctenocephalides. Genus Ceratophyllus. Nosopsyllus Pulex.

The genome of retroviruses contains three major coding regions for virion proteins, gag, pol and env. Gag encompasses information for nonglycosylated viral proteins that form the matrix, the capsid and the nucleoprotein structures. From pol derive reverse transcriptase and integrase, and env codes for the surface glycoproteins of the virion which consist of a transmembrane and a surface domain, linked by disulfide bonds. A viral protease is derived eitherfrom the gagorfrom the pol coding region, depending on the virus. Simple retroviruses contain only this elementary gag, pol, and env coding information. Once integrated, they are able to multiply efficiently, using the cellular transcriptional and replication machineries without intervention of viral transacting factors. Most oncogenic retroviruses belong in this category. Complex retroviruses, on the other hand, encode additional nonstructural proteins from multiply spliced messages. These proteins play important regulatory roles in the life cycle of the virus. They function as transacting factors that, in concert with cellular regulatory proteins, control viral gene expression and function and are essential components in the replication of complex retroviruses. To this category belong the lentiviruses, the spumaviruses and a group of oncogenic retroviruses that includes human T cell leukemia virus (HTLV) and bovine leukosis virus(BLV).

The recent rapid advances in our knowledge of immunological and virological mechanisms involved in the pathogenesis of viral heart disease makes it difficult for everybody working in this field to keep up with the latest developments. How ever, much of what we know is still circumstantial and only vaguely substained. Interdisciplinary understanding and cooperation thus seems necessary to get a better insight into the mechanisms by which viruses may initiate immunological organ-specific tissue injury and disease! This volume evolved out of an international symposium by the same title held on May 25. -28. , 1988 in Tegernsee, near Munich, of which a wide spectrum ofim munological, virological, diagnostical and clinical problems was covered. Both review articles and new experimental and clinical data are included in this volume to give the reader an up-to-date information about current concepts and future aspects. Chapter I serves as an excellent introduction to the epidemiology and natural history of dilated cardiomyopathy / viral heart disease. Although a definite viral etiology in myocarditis and dilated cardiomyopathy is often difficult to establish, epidemiological and serological data incriminate a viral etiology underlying many cases of "dilated cardiomyopathy". Chapters II and III describe the current think ing on virological and immunological mechanisms involved in the pathogenesis of viral heart disease. Among others virus topism, virus persistance, possible mecha nisms and genetic basis of post-infection autoimmunity, and the virus-interaction with the immune system are discussed.

During recent years there has been increasing interest in the value of a number of chemical and physical-chemical analytical methods for the detection and characterization of microorganisms. Furthermore, such methods are currently used in studies on microbial metabolic processes, on the role of microorganisms in the turnover of inorganic and organic compounds, and on the impact on environmental changes by microbial activity. Moreover, the introduction of some of these methods not only shortens the analytical time period compared to *'traditional" techniques, but also improves the analytical quality. Mass spectrometry (MS) combined with chromatographic inlet systems, particularly gas chromatography (GC), belongs to those methods which during recent years have established their value for the above-mentioned purposes. The present volume starts with basic chapters on the principles for MS and common inlet systems, particulary Gc. It discusses applications of these techniques to a number of microbiological disciplines, e.g., ecologi cal and medical microbiology. Emphasis is laid on organic compound classes vii viii / PREFACE of special relevance to microbiology, e.g., volatiles, lipids, amino acids, peptides and carbohydrates. Some compound classes of a more general biochemical rather than specific microbiological importance, e.g., steroids and nucleotides, are dealt with briefly. The editors wish to thank all those who have contributed to this book. We hope it will stimulate further research in this futuristic field and will be of practical value.

Borna disease was first described over 200 years ago, in what is now Southeastern Germany, as a fatal neurologic affliction of horses and was considered a curiosity for many decades. The causative agent was unknown, and the animal species infected in nature were limited to horses and sheep. Today, as described in this volume, the host range has extended to all warm-blooded animals, the genes and proteins of the virus have been identified, and many of the mechanisms responsible for behavioral disturbances are understood. Serologic studies suggest that BDV or related agents are likely to play a role in human neuropsychiatric diseases.

For decades this virus system has served--and continues to do so--to pioneer investigations on the molecular biology, biochemistry and genetics of mammalian cell systems. This three volume work presents an up-to-date account of recent basic research in one of the most important experimental systems for biochemical, cell biological, genetic, virological and epidemiological investigations in mammalian molecular biology. In this, the second of three volumes, the attention is turned to such topics as DNA replication, recombination and integration, and post-transcriptional control. The chapters have been written by an international group of leading experts in their respective fields of interest.