Twenty-eight contributions topics and authors spanning the disciplines of microbiology, biochemistry, molecular biology, and medicine present what is known in an area that has important implications for aspects of biomedical research. Investigations of the mechanisms of action of the ADP-ribosylatin

In recent years remarkable progress has been accomplished with respect to our knowledge about bacterial protein toxins. This refers especially to structural aspects of protein toxins but also holds true for genetics, molecular biology and biochemical mechanisms underlying the action of toxins. This volume covers the very current and exciting aspects of up-to-date bacterial toxicology and comprehensively reviews the most important bacterial protein toxins such as the intracellular acting toxins which exhibit enzyme activity, as well as those toxins that interact with cell plasma membranes by damaging the membranes (pore formation) or stimulating cell receptors (superantigens). This is the most current reference work on these important bacterial protein toxins, which are presented from the point of view of different disciplines such as pharmacology, microbiology, cell biology and protein chemistry.

ADP-ribosylating toxins have been the focus of intensive research for more than 30 years. Researchers from diverse fields of science have taken an interest in these bacterial toxins; they are studied, for example, by microbiologists, biochemists, cell biologists, and pharmacologists. There are two principal reasons for the broad and still growing interest in ADP ribosylating toxins. First, insights into the structure and functions of the toxins might be the key to prevention and treatment of diseases caused by the toxin-producing infectious micro organisms. Second, the ADP-ribosylating toxins provide potent and often unique pharmacological tools for the study of the physiological functions of their target proteins. The latter is especially the case with cholera and pertussis toxins, which both modify the IX-subunits of heterotrimeric G-proteins involved in signal transduction pathways. These toxins have proved invaluable in extending our basic understanding of the regulation of hormone-controlled signal transduction. This volume provides a review and an update of recent studies on the basic properties of bacterial ADP-ribosylating tbxins and/or exoenzymes. Our current knowledge of the cel lular entry mechanisms of ADP-ribosylating toxins is reviewed by MADSHUS and STENMARK. WILSON and COLLIER then deal with recent insights into the enzyme mechanism and active site structure of diphtheria toxin and Pseudomonas aeruginosa exotoxin A, which modify elongation factor 2. Toxins which ADP-ribosylate heterotrimeric G-proteins involved in trans membrane signal transduction are the subject of the next two chapters.

This book describes the major achievements and discoveries relevant to bacterial protein toxins since the turn of the new century illustrated by the discovery of more than fifty novel toxins (many of them identified through genome screening). The establishment of the three-dimensional crystal structure of more than 20 toxins during the same period offers deeper knowledge of structure-activity relationships and provides a framework to understand how toxins recognize receptors, penetrate membranes and interact with and modify intracellular substrates. - Edited by two of the most highly regarded experts in the field from the Institut Pasteur, France - 14 brand new chapters dedicated to coverage of historical and general aspects of toxinology - Includes the major toxins of both basic and clinical interest are described in depth - Details applied aspects of toxins such as therapy, vaccinology, and toolkits in cell biology - Evolutionary and functional aspects of bacterial toxins evaluated and summarized - Toxin applications in cell biology presented - Therapy (cancer therapy, dystonias) discussed - Vaccines (native and genetically engineered vaccines) featured - Toxins discussed as biological weapons, comprising chapters on anthrax, diphtheria, ricin etc.

The Comprehensive Sourcebook of Bacterial Protein Toxins, Fourth Edition, contains chapters written by internationally known and well-respected specialists. This book contains chapters devoted to individual toxins, as well as chapters that consider the different applications of these toxins. Considerable progress has been made in understanding the structure, function, interaction and trafficking into cells, as well as mechanism of action of toxins. Bacterial toxins are involved in the pathogenesis of many bacteria, some of which are responsible for severe diseases in human and animals, but can also be used as tools in cell biology to dissect cellular processes or used as therapeutic agents. Novel recombinant toxins are already proposed in the treatment of some diseases, as well as new vaccines. Alternatively, certain toxins are also considered as biological weapons or bioterrorism threats. Given the multifaceted aspects of toxin research and the multidisciplinary approaches adopted, toxins are of great interest in many scientific areas from microbiology, virology, cell biology to biochemistry and protein structure. This new edition is written with a multidisciplinary audience in mind and contains 5 new chapters that reflect the latest research in this area. Other chapters have been combined, deleted and fully revised as necessary to deliver relevant and valuable content. - Descriptions of relevant toxins as well as representative toxins of the main bacterial toxin families to allow for a better comparison between them - Focused chapters on toxin applications and common properties or general features of toxins

Bridging the gap between laboratory observations and industrial practices, this work presents detailed information on recombinant micro-organisms and their applications in industry and agriculture. All recombinant microbes, bacteria, yeasts and fungi are covered.

Molecular Action of Toxins and Viruses investigates the molecular action of bacterial toxins and viruses and its striking similarity to the mechanisms by which many neural and hormonal stimuli control normal cell functions. Topics covered include the biological activity of diphteria toxin; the role of cholera toxin in the regulation of hormone-sensitive adenylate cyclase; toxic lectins and related proteins; and bacterial cytolysins (membrane-damaging toxins). Comprised of nine chapters, this volume begins with a discussion on the biosynthesis and biological activity of diphtheria toxin, toxin-resistant mutant cells, and the entry of toxin into cells and fragment A in the cytoplasm of living cells. The reader is then systematically introduced to the use of cholera toxin as a probe to study the regulation and interaction of adenylate cyclase components; the toxic action of lectins and related proteins such as abrin, ricin, and modeccin; and the ability of bacterial cytolysins to damage cell membranes. The remaining chapters focus on the mechanism of action of colicin E2, colicin E3, and cloacin DF13; similarities in the action of different bacterial toxins; the role of cell membranes in infection with bacterial viruses and colicins; and the life cycle and infection mechanisms of bacteriophage T4. The book concludes with an analysis of the involvement of protein kinases in viral transformation. This monograph will be of interest to students, practitioners, and researchers in fields ranging from molecular biology and biochemistry to cell biology, bacteriology, and physiology.

This is a survey of well characterized and recently discovered bacterial protein toxins. Leading investigators of the respective toxins review the various molecular mechanisms of action, ranging from toxin-induced ADP-ribosylation up to membrane perforation by pore-forming toxins. Thy also describe the consequences on host physiology before focusing on potential applications as cell biological and pharmacological tools for research and medical applications. Detailed descriptions of the methodology include the engineering and use of modified and chimeric toxins for better performance. A solid introduction to toxin structure and functions, as well as a valuable source of methodology for researchers in molecular biology, pharmacology and experimental medicine.

Considering the current interest in cellular regulation and intracellular signalling systems, it is surprising that the contribution of ADP-ribosylation reactions to the modulation of a variety of specific cell processes, in parallel with other post-translational modifications such as phosphorylation, has not been generally recognized. While it is not feasible to cover all aspects of ADP-ribosylation, the thirty-one articles contained in this volume provide a valuable overview of recent progress in the field within the context of cell control mechanisms. For the convenience of the reader, the various topics have been grouped into several sections: (a) poly(ADP-ribosyl)ation; (b) mono-ADP-ribosylation; (c) toxin mono-ADP-ribosylation; (d) inhibitors and activators; (e) protein modification with ADP-ribose and its analogues; and (f) non-modification forms of ADP-ribose. The contents of the individual chapters reflect the ideas of the contributors, many of whom have spent their careers attempting to resolve the biological functions of ADP-ribosylation. We hope that this publication will serve as a useful reference for those investigators that are new to the area as well as those who are actively studying ADP-ribosylation.