Bacterial Virulence Factors And Rho Gtpases

Pathogenic bacteria for human and animals have developed sophisticated weapons, termed virulence factors, to ensure their replication and persistence into their hosts. The authors in this volume show a synthesis on how the various host cellular Rho GTPases activities are manipulated by bacteria to fulfil their virulence.

Mass immunization is the blitzkrieg of vaccination practice. It serves to rapidly protect populations, both because of the high coverage achieved and because of the herd immunity thereby induced. However, as in war, mass immunization campaigns must be conducted intelligently, with careful strategy and strong attention to logistics of supply and deployment. If conducted badly, mass immunization may fail or even be counter-productive. In this volume, some of the most successful practitioners of mass im- nization tell us about its art and science. David Heymann and Bruce Aylward of WHO begin the book with a theoretical and practical overview of mass immunization. Michael Lane, who participated in the successful effort to eradicate smallpox relates how this was done using mass vaccination and other strategies. Application of mass immunization by the US military is c- ered by John Grabenstein and Remington Nevin, who have a large experience in these matters. Karen Noakes and David Salisbury recount the striking s- cesses of mass immunization in the United Kingdom. The global control of the clostridia that produce diphtheria toxin is described by Charles Vitek. Hepa- tis A is decreasing dramatically under the impact of large-scale vaccination, as Francis André illustrates. The French experience with Hepatitis B vac- nation has been mixed, and François Denis and Daniel Levy-Bruhl explain the circumstances. In?uenza vaccination is an annual example of large-scale campaigns, the complexity of which is recounted by Benjamin Schwartz and Pascale Wortley.

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.

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.

The Comprehensive Sourcebook of Bacterial Protein Toxins 4th 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.

Most studies of bacterial or fungal infectious diseases focus separately on the pathogenic microbe, the host response, or the characterization of therapeutic compounds. Compartmentalization of pathogenesis-related research into an analysis of the “pathogen”, the “host,” or the “antimicrobial compound” has largely been dictated by the lack of model systems in which all of these approaches can be used simultaneously, as well as by the traditional view that microbiology, immunology, and chemical biology and pharmacology are separate disciplines. An increasing number of workers from different fields have turned to insects, fish, worms and other model hosts as facile, ethically expedient, relatively simple, and inexpensive hosts to model a variety of human infectious diseases and to study host responses and innate immunity. Because many of these hosts are genetically tractable, they can be used in conjunction with an appropriate pathogen to facilitate the discovery of novel features of the host innate immune response. This book provides a series of reports from the 1st International Conference on Model Hosts. This first of its kind meeting focused on invertebrate, vertebrate and amoeboid systems used for the study of host-pathogen interactions, virulence and immunity, as well as on the relevance of these pathogenesis systems and mammalian models. Importantly, a common, fundamental set of molecular mechanisms is employed by a significant number of microbial pathogens against a widely divergent array of metazoan hosts. Moreover, the evolutionarily conserved immune responses of these model hosts have contributed important insights to our understanding of the innate immune response of mammals. This book provides a series of reports from the 1st International Conference on Model Hosts. This first of its kind meeting focused on invertebrate, vertebrate and amoeboid systems used for the study of host-pathogen interactions, virulence and immunity, as well as on the relevance of these pathogenesis systems and mammalian models. Importantly, a common, fundamental set of molecular mechanisms is employed by a significant number of microbial pathogens against a widely divergent array of metazoan hosts. Moreover, the evolutionarily conserved immune responses of these model hosts have contributed important insights to our understanding of the innate immune response of mammals.

This volume describes the mechanisms which bacteria have created to secure their survival, proliferation and dissemination by subverting the actin cytoskeleton of host cells. Bacteria have developed a veritable arsenal of toxins, effector proteins and virulence factors that allow them to modify the properties of the intracellular actin cytoskeleton for their own purposes. Bacterial factors either modify actin directly as the main component of this part of the cytoskeleton or functionally subvert regulatory or signalling proteins terminating at the actin cytoskeleton. In short, this volume provides an overview of the various tricks bacteria have evolved to “act on actin” in order to hijack this essential host cell component for their own needs. As such, it will be of interest to scientists from many fields, as well as clinicians whose work involves infectious diseases.

Rho GTPases control many aspects of cell physiology. This includes polarity, endo/exocytosis, adhesion, motility, transcriptional activation, cell cycle progression or apoptosis. In view of such pleiotropic activities, Rho-controlled signaling has proven to be of medical relevance, especially in tumorigenesis, disease-associated bone remodeling and infectiology. This book is divided into three parts. Part 1 gives an evolutionary perspective of the Rho family, its atypical members, and an overview of how Rho activity is regulated. Part 2 addresses two important aspects of multicellularity controlled by Rho-dependent pathways, namely, cell-cell interactions and mechanotransduction. It also describes how post-translational modifications control Rho activity and how this is exploited by pathogenic bacteria. Part 3 explores several examples of the variety of pathophysiological processes controlled by Rho signaling, and gives a successful example of translational research, from the inhibition of Rho activation to the development of new molecules against osteoporosis. This updated review on the biology of Rho GTPases is an essential read for molecular and cell biologists. It is also an invaluable guide to post-graduate and medical students who wish to deepen their knowledge in cell biology. Contents: An Historical and Evolutionary PerspectiveAtypical Rho GTPases in Health and DiseaseRegulators of Rho SignalingRho GTPases in Cadherin-Based Cell-Cell InteractionsRho Signaling in MechanotransductionPost-Translational modifications of Rho GTPasesRhoA Mutations in Cancer: Oncogenes or Tumor-SuppressorsModulation of Osteoclast Differentiation and Function by Rho GTPasesRhoGEFs as Therapeutic TargetsEndothelial-Specific Rho GTPase Signaling During Leukocyte Extravasation Readership: Molecular and cell biologists, post-graduate and medical students interested in cell biology. Keywords: Rho GTPases;Signaling Oathways;F-actin;Cytoskeleton;Adhesion;Migration;CancerReview: Key Features: Different integration levels for a better understanding of biological and pathological implications of Rho signalingChapters cover updated and original Rho-controlled aspects of cell biologyContributors are leaders in their fields of research