Bacterial Pathogenesis: Molecular and Cellular Mechanisms | Book
Caister Academic Press
Camille Locht and Michel Simonet Center for Infection and Immunity of Lille, University of Lille Nord de France, Institut Pasteur de Lille, France
x + 370 (plus colour plates)
January 2012Buy hardbackAvailable now!
GB £180 or US $360
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One of the greatest public health achievements during the twentieth century was the dramatic reduction in the incidence of infectious diseases due to the development of improved hygiene, vaccines and antimicrobial agents. However, new infectious diseases are emerging and bacteria-induced illnesses, such as tuberculosis, whooping cough and typhoid fever, are still a major cause of global mortality. In recent decades the development of molecular biology and genetic tools has led to extensive studies on the molecular and cellular aspects of the virulence properties of pathogenic bacteria.
In this book, a group of distinguished scientists from eight different countries and three continents, under the expert guidance of the editors Camille Locht and Michel Simonet, overview the molecular and cellular mechanisms of bacterial pathogenesis. The fifteen chapters are organized into five sections: approaches to the study of bacterial pathogenesis; bacterial adhesion to the cell surface and extracellular matrix of host tissues; poisoning the host by toxins; cellular invasion by bacterial pathogens; and bacterial evasion of host defences. The authors comprehensively describe the most relevant and up-to-date information on pathogenic features across the bacterial world. Aimed at the entire scientific community from students to senior scientists and physicians, the book is relevant to a broad range of people interested in the mechanisms of bacterial infectious diseases and is a recommended text for all microbiology laboratories.
"a valuable book for both graduate students and mature scientists working in the field of bacterial pathogenesis. The authors are all highly accomplished scientists and have carefully shared their work in a logical and comprehensive manner ... useful to those in many areas of research" from Rebecca T. Horvat (University of Kansas, USA) writing in Doodys
"The book is aimed primarily at advanced students and experienced scientists looking for concise overview articles and extensive reference lists." from Andreas Peschel (Tuebingen, Germany) writing in Biospektrum (2012) 18: 342-343.
"useful to those in many areas of research" (Doodys); "concise overview articles" (Biospektrum)
Approaches to the Study of Bacterial Pathogenesis
Models for Studying Bacterial Pathogenesis
Richard W. Titball and Olivia L. Champion
Research into mechanisms of virulence underpins work to devise improved control measures for infectious diseases. However, the ability of a pathogen to cause disease is implicitly dependent not only on the bacterial species but also on the host. Without the availability of a suitable experimental host, studies on mechanisms of virulence either cannot proceed or cannot be interpreted in an appropriate contextual manner. This chapter considers the advantages and disadvantages of different hosts, including mammals, zebra fish, plants, Caenorhabditis elegans, insects such as Drosophila melanogaster and Galleria mellonella, and cell culture systems for investigating mechanisms of virulence of pathogens which cause disease in humans. The potential for gaining additional information and using fewer animals in experiments involving mammals is reviewed, with a particular emphasis on the potential for new imaging techniques to provide additional information. Much of this information will of course be of relevance to pathogens which are associated with diseases in non-human hosts.
Strategies for Identifying Bacterial Pathogenicity Genes
Raphael H. Valdivia
The identification of factors that enhance the virulence of bacteria is a critical step in understanding the molecular basis for their pathogenesis. Over the last several years, molecular and genetic strategies have been developed to identify bacterial virulence determinants. These approaches, combined with rapidly advancing genome technologies, have allowed investigators to map the pathogen's transcriptional responses to the host environment and to define the relative contribution of individual genes to the infectious process. This chapter highlights some of the many approaches currently under use. Genes that enhance the ability of bacteria to infect, to evade host immune responses, and to disseminate are commonly referred to as virulence genes. These genes may encode factors ranging from toxins and adhesins, with readily recognized roles in disease causation, to enzymes that enhance the pathogen's metabolic properties within the host's nutrient-limiting environment. Identifying virulence genes and determining the function of their encoded products is central to our understanding of microbial pathogenesis.
Genetic Determinants of Bacterial Pathogenicity
Gavin K. Paterson and Duncan J. Maskell
Determinants of bacterial pathogenicity are encoded by different types of genetic elements. Of particular note are large loci including pathogenicity islands, bacteriophages, integrative and conjugative elements, plasmids and integrons. Gene loss can also play a significant role in determining bacterial pathogenicity and should not be disregarded. Here we discuss these main genetic determinants of bacterial pathogenicity and how they influence the behaviour of important human and veterinary pathogens. The chapter illustrates the vast diversity and adaptability of bacterial pathogens, features that will ensure their continued medical and veterinary importance for quite some time to come.
Bacterial Adhesion to the Cell Surface and Extracellular Matrix of Host Tissues
Fimbrial Adhesins: Adhesive Molecules on a 'Stalk'
Hae Joo Kang, Edward N. Baker and Thomas Proft
As an important step for the successful and continuous colonization of the host, bacterial pathogens express a variety of specific adhesins on their cell surface, which allows them to interact with receptors on host cells. However, this close interaction might also be detrimental for the bacteria, as it could trigger infiltration and activation of immune cells and eventually lead to phagocytosis. Another obstacle for colonization is electrostatic repulsion due to the negative surface charge on both the bacteria and the host cell. Many bacteria have overcome this problem by expressing adhesins at the tip of a long fibril structure that extends from the bacterial cell surface. These structures are known as fimbriae or pili. Despite their diversity in structure and biogenesis, pili/fimbriae typically consist of a long fiber formed by homopolymerised subunits or pilins, and accessory pilins that often function as adhesins. Some pili are also involved in cell aggregation, biofilm formation, DNA uptake, phage transduction and gliding motility.
Nonpilus (Non-Fimbrial) Adhesins
Amanda J. Sheets and Joseph W. St. Geme III
Adherence to a biological surface allows bacteria to persist and spread within the host and represents an essential early step in the pathogenesis of most bacterial diseases. Bacteria produce a variety of pilus and non-pilus adhesive structures that mediate specific adherence to host tissues. Among non-pilus adhesive structures, most can be classified according to the mechanism of secretion or the mechanism of anchoring to the bacterial surface. The majority of non-pilus adhesins are proteins, but other structures such as lipopolysaccharide and lipoteichoic acid also have adhesive function. This chapter summarizes the classes of bacterial non-pilus adhesins and highlights the roles of prototype adhesins in the context of disease pathogenesis. Elucidation of conserved mechanisms of secretion and anchoring of adhesins may facilitate the development of novel therapeutic agents that combat infectious diseases by effectively disrupting adherence and initial interactions with the host.
Biofims: the Secret Story of Microbial Communities
Christophe S. Bernard, Caroline Giraud, Jennifer Spagnolo, and Sophie de Bentzmann
This chapter is dedicated to a particular phase of the bacterial cell cycle known as the biofilm, in which single-celled individuals gather together to form a sedentary but dynamic community with a complex structure, displaying spatial and functional heterogeneity. In response to the perception of environmental signals by sensing systems, appropriate responses are triggered, leading to biofilm formation. This process involves various molecular systems (described in detail here for Gram-negative and Gram-positive bacteria) enabling bacteria to identify appropriate surfaces on which to anchor themselves, to stick to those surfaces and to each other, to construct multicellular communities several hundreds of micrometers thick and to detach from the community. These molecular systems are used antagonistically or synergistically, depending on the microenvironment confronting the bacterium. The biofilm microbial community is a unique, highly competitive and crowded environment facilitating microevolutionary processes and horizontal gene transfer between distantly related microorganisms. It is governed by social rules, based on the production and use of "public" goods, with actors and recipients. Biofilms constitute a unique shield against external aggressions, including drug treatment and immune reactions. Biofilm-associated infections in humans have therefore generated major problems for the diagnosis and treatment of disease. Improvements in our understanding of biofilms have led to innovative research aiming to interfere with the process of biofilm formation.
Poisoning the Host by Toxins
Toxins Damaging Cellular Membranes: Paradigms and Molecular Features
Joseph E. Alouf
The repertoire of the bacterial cytolytic pore-forming protein toxins (PTFs) comprises ca. 86 identified members produced by both Gram-positive and -negative bacteria. The essential functional feature of these cytolysins is their capacity to provoke the formation of hydrophilic pores in the cytoplasmic membranes of target eukaryotic cells. This process results from the binding of the proteins on the cell surface, followed by their oligomerization, which leads to the insertion of the oligomers into the membrane and formation of protein-lined channels. This insertion provokes the impairment of the osmotic balance of the cell and subsequent cytolysis. The classification and molecular aspects of a number of important PTFs are described, as well as the pathophysiological features of some of these cytolysins and their relation to human diseases.
Toxins Acting on Intracellular Targets: Only Foes or Also Friends?
Teresa Frisan, Riccardo Guidi, Lina Guerra
Bacteria possess an arsenal of virulence factors that allow them to colonize, invade and replicate within hostile niches, such as immunocompetent individuals. Bacterial toxins are among the most sophisticated virulence factors. They are highly specific for their target. Specificity is defined at the level of the target cell (presence of the receptor) and at the level of the substrate, since most of them are enzymes and require specific protein-protein interactions to exert their toxic activity. Some of them are also very powerful, and are among the most toxic compounds known to date. To gain access to their targets within the host cell, these molecules have exploited all the possible cellular routes of internalization: from direct translocation through the plasma membrane, to retrograde transport through the Golgi complex and the endoplasmic reticulum. Identification of their mode of action, their receptors and internalization routes has been instrumental to understand the role of toxins in the pathogenesis of bacteria-induced diseases, and has allowed production of prophylactic vaccines. Last but not least, bacterial toxins have been and are still used as tools in biomedical research to characterize basic cellular processes.
Cellular Invasion by Bacterial Pathogens
Mechanisms of Bacterial Entry Into Host Cells
Kevin Moreau and Frank Lafont
Most invading bacteria enter the host cell by using either a triggered or a zippered mechanism. The former depends on membrane ruffles induced by injection of bacteria-derived effectors into the eukaryotic cell. A hallmark of the latter is a "sliding" of the bacteria into the cell through a clathrin-mediated structure, which is distinct from the pits in conventional clathrin-mediated endocytosis. Bacteria hijacking either of these mechanisms can also take advantage of signalling platforms activated within specialized membrane domains (lipid rafts). At the entry site, activated signalling pathways regulate the fate of the invading microorganism. Bacteria may then replicate in either cytoplasmic or vacuolar niches. Alternatively, the host immune system can deal with the infection and target the pathogen for elimination via several degradation pathways (notably including autophagy).
The Bacterial Life in a Vacuole
Ana Rita Furtado and Agathe Subtil
Several intracellular bacteria survive and multiply inside membrane-bounded compartments called vacuoles. While this lifestyle offers several advantages against host cell defenses, it also imposes important constraints. Pathogens have developed independent strategies to survive within their host, and as a consequence, each "vacuole" is unique to a given bacterium in its composition and behavior. However, common requirements and strategies emerge. We describe how intracellular pathogens interact with the host trafficking pathways to transform their vacuole into a favorable niche, and undermine the host defense mechanisms against intruders. This is mainly achieved through the action of bacterial proteins translocated out of the vacuoles into the host cytoplasm. An increasing number of these "effector" proteins are currently being identified, and the functions of a few of them start to be understood.
The Bacterial Life in the Cytosol
Serge Mostowy and Pascale Cossart
To live inside host cells and replicate, pathogenic bacteria can either establish a niche in a vacuolar compartment or escape to the cytosol. In this chapter, we review our understanding of pathogenic mechanisms to escape and live in the cytosol, and highlight recent studies of bacterial survival strategies to counteract intracytosolic host defences.
Bacterial Evasion of Host Defences
Bacterial Handling of Host Nutrients: the Iron Paradigm
Pathogenic bacteria must compete with their host for iron. The host lowers serum iron levels during inflammation and binds iron with high affinity to transferrin and lactoferrin, thereby limiting iron availability for the pathogens. Under such iron-limiting conditions, many pathogens, like their non-pathogenic relatives, secrete iron chelators, called siderophores, which mobilize even traces of iron for the bacteria. The host combats catecholate siderophores of various pathogens by avidly binding the chelator to the host protein siderocalin. Pathogenic bacteria can evade this host mechanism in one or more ways: secreting other siderophores that are not bound by siderocalin, utilizing heme as an iron source, and transporting ferrous iron. All these uptake systems are regulated by the general iron needs of bacteria and fine tuned according to the surrounding supply of iron-containing compounds. Iron limitation is also a signal for many pathogens to produce toxins and other virulence factors. When one iron supply system is disabled, virulence is often only mildly attenuated. Although it has long been known that iron is required for the infection process, no therapeutics directed at this have been marketed yet.
Bacterial Escape from the Complement System
Marta Biedzka-Sarek and Mikael Skurnik
Bacterial infections represent a global health problem. To establish infection bacteria need to defeat the action of the non-specific immune system machinery. Its essential component, activated immediately upon pathogen entry, is the complement system. Complement activation (through the classical, the lectin, and the alternative pathways) tags microbes for destruction by phagocytic cells, causes microbial lysis, and leads to generation of downstream proinflammatory responses. Moreover, vaccination or pre-exposure to a given microbe is not required for the complement system to eliminate the intruder. Many bacteria have, however, developed strategies to evade the complement system. Investigating these processes should further our understanding of host-bacterium interactions and contribute to prevention and treatment of bacterial infections.
Bacterial Resistance to Antimicrobial Peptides
John D. F. Hale
Host defence peptides (HDP) are small cationic, amphipathic molecules produced by all organisms as a first line of defence against microbial invasion and are commonly found at host-microbe interfaces, such as epithelial layers. Although initially identified to control microbial levels through direct antimicrobial activity, their role has been expanded to include the multitude of other functions including modulation of innate defence factors. While HDPs are active against a range of microbes, the best understood resistance mechanisms are in bacteria. Many pathogenic bacteria have evolved resistance mechanisms to ensure their own survival and an increased virulence following continual exposure to HDPs. Although individual species can affect resistance differently, they still fall under certain themes, such as repulsion, degradation, sequestration and expulsion, all of which are based the exploitation of the common features of HDPs, such as charge or their peptide nature. Despite this diverse range of resistance mechanisms, bacteria have yet to achieve full resistance to the large repertoire of HDPs.
Bacteria-Induced Host Cell Death
Scott D. Kobayashi, Kevin M. Rigby and Frank R. DeLeo
The interaction of bacteria with host cells largely dictates the outcome of infection. Whether following a breach in the epithelium or by dissemination from colonized tissues, bacteria interact directly with immune and non-immune host cells. Therefore, it is perhaps not surprising that bacteria implement multiple strategies to circumvent destruction or avoid detection by the host. One such strategy is the ability of bacteria to alter host cell apoptosis or cause other forms of cell death. Although some bacterial pathogens induce or delay cell death and thereby promote disease, bacteria-induced cell death can also be beneficial to the host. This topic is reviewed in the present chapter.
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(EAN: 9781904455912 Subjects: [microbiology] [bacteriology] [medical microbiology] [molecular microbiology] )