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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.
Bacterial pathogenicity factors are functionally diverse. They may facilitate the adhesion and colonization of bacteria, influence the host immune response, assist spreading of the bacterium by e.g. evading recognition by immune cells, or allow bacteria to dwell within protected niches inside the eukaryotic cell. Exotoxins can be single polypeptides or heteromeric protein complexes that act on different parts of the cells. At the cell surface, they may insert into the membrane to cause damage; bind to receptors to initiate their uptake; or facilitate the interaction with other cell types. For example, bacterial superantigens specifically bind to major histocompatibility complex (MHC) II molecules on the surface of antigen presenting cells and the T cell receptor, while cytolysins cause pore formation. For intracellular activity, exotoxins need to be translocated across the eukaryotic membrane. Gram-negative bacteria can directly inject effector proteins in a receptor-independent manner by use of specialized needle apparatus such as bacterial type II, III, or type IV secretion systems. Other methods of translocation include the phagocytic uptake of bacteria followed by toxin secretion, or receptor-mediated endocytosis which allows the targeting of distinct cell types. Receptor-based uptake is initiated by the binding of heteromeric toxin complexes to the cell surface and completed by the translocation of the effector protein(s) across the endosomal membrane. In the cytosol, toxins interact with specific eukaryotic target proteins to cause post-translational modifications that often result in the manipulation of cellular signalling cascades and inflammatory responses. It has become evident that the actions of some bacterial toxins may exceed their originally assumed cytotoxic function. For example, pore-forming toxins do not only cause cytolysis, but may also induce autophagy, pyroptosis, or activation of the MAPK pathways, resulting in adjustment of the host immune response to infection and modification of inflammatory responses both locally and systemically. Other recently elucidated examples of the immunomodulatory function of cell death-inducing exotoxins include TcdB of Clostridium difficile which activates the inflammasome through modification of cellular Rho GTPases, or the Staphyloccocus d-toxin which activates mast cells. The goal of this research topic was to gather current knowledge on the interaction of bacterial exotoxins and effector proteins with the host immune system. The following 16 research and review articles in this special issue describe mechanisms of immune modification and evasion and provide an overview over the complexity of bacterial toxin interaction with different cells of the immune system.
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.
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.
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
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.
Bacterial Pathogens and their Virulence Factors contains a detailed description of 32 major bacterial pathogens that affect human health and their associated virulence determinants. Chapter 1 gives an overview of the different types and classes of general virulence factors involved in host cell adherence and invasion, dissemination within the host, host cell damage, and evasion of host defense systems, as well as mechanisms by which these virulence factors are regulated. Chapters 2 through 33 give concise descriptions of the disease states associated with the 32 bacterial genera and their major pathogenic species, along with an in-depth description of the individual virulence factors that have been found to be functionally involved in pathogenicity. A detailed bibliography derived from primary literature and review articles accompanies each of these chapters, allowing the reader to delve more deeply into individual pathogens and their virulence determinants. Chapter 34 discusses the exciting possibilities and initial successes of using detailed information on a pathogen’s virulence toolkit to design new therapeutics aimed at specific virulence traits.