Pathogenic Escherichia coli: Molecular and Cellular Microbiology | Book
Caister Academic Press
Stefano Morabito EU Reference Laboratory for E. coli, Veterinary Public Health and Food Safety Department, Istituto Superiore di Sanità, Rome, Italy
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In recent years we have accumulated a great deal of knowledge on the features associated with virulence of pathogenic E. coli. A large number of virulence genes have been identified and their products characterised. Great strides have been made in our understanding of the pathogenic mechanisms and the bacterium-host interaction. However, much remains elusive in our understanding of pathogenicity at a cellular and sub-cellular level. This is largely due to E. coli genome's plasticity: it generates great variability and facilitates the rapid emergence of new pathogenic variants. Elucidating the mechanisms underlying the evolution of these pathogens and their interactions with the host are key stages for disease prevention.
This book reviews the most important recent findings of the studies on pathogenic E. coli providing a timely overview of the field. Topics covered include: epidemiology of the disease in humans and animals and the biological mechanisms that shaped the pathogenic types of E. coli; shiga toxins; subtilase cytotoxin; cell cycle modulating toxins; the heat stable and heat labile enterotoxins; haemolysins; structural, molecular and functional characteristics of A/E lesions; colonization factor antigens of ETEC; enteroaggregative adhesion; host cell invasion; and the development of vaccinal strategies to confront the burden of disease. Chapters are written from a molecular and cellular biology standpoint but also include discussions of the findings with a wider perspective including considerations on public health and the impact on animal productions. Essential reading for everyone working on these and related pathogens.
"... an excellent textbook. It is current, comprehensive, and a great resource ... comprehensive, informative, and well referenced ... a worthwhile investment for those interested in the molecular and cellular microbiology of pathogenic E. coli." from Rodney A. Moxley (Lincoln NE, USA) writing in Vet Med Today JAVMA (2014) 245: 658.
"current, comprehensive, and a great resource" (JAVMA)
"No abstract is available for the Foreword. The first two paragraphs are presented instead: Theodor Escherich described, at the end of the XIX century, a bacterium isolated from stool samples of healthy infants that he named Bacterium coli commune. This happened a decade after Robert Koch proved the association between microbes and disease. At that time Bacterium coli commune, later named Escherichia coli after the man who discovered it, was considered basically a commensal bacterial species and it took other fifty years for it to be associated with a human infection. Today E. coli is known as one of the bacterial species with the widest adaptability to an amazing variety of niches either within organisms or outside in the environment. As a matter of fact it colonizes the gastrointestinal tract of humans and warm-blooded animals during the first phases of the life establishing mutual beneficial relationships with the host and playing an important role in maintaining the equilibrium between the numerous bacterial species constituting the gut microflora. At the same time, E. coli is one of the most diffuse bacterial species in the environment, being present in almost all the niches including water and soil.
Diarrheagenic Escherichia coli Infections in Humans
Rosangela Tozzoli and Flemming Scheutz
Escherichia coli is the predominant component of the mammals' gastrointestinal tract microbiota. It is usually a harmless commensal. Nevertheless, some strains have evolved the capability to cause disease in humans and are subdivided in groups depending on which part of the body they affect and of their particular pathogenic mechanism. Clinical syndromes resulting from infection with pathogenic E. coli strains include: (i) urinary tract infection, (ii) sepsis/meningitis, and (iii) enteric/diarrheal disease. Strains causing the first two clinical syndromes are altogether termed Extraintestinal Pathogenic E. coli (ExPEC), whereas the strains inducing gastroenteric disease are known as Diarrheagenic E. coli (DEC). DEC are subdivided in different pathotypes based on their adhesion/colonization mechanism and the toxins produced, which are: Enteropathogenic E. coli (EPEC), Enterotoxigenic E. coli (ETEC), Enteroinvasive E. coli (EIEC), Enteroaggregative E. coli (EAggEC), Diffusely Adherent E. coli (DAEC), and Shiga toxin-producing E. coli (STEC), which are also referred to as Verocytotoxin-producing E. coli (VTEC). This chapter focuses on the human infections caused by DEC, providing general knowledge on the virulence traits and pathogenic mechanisms, the symptoms induced, known incidence and routes of transmission of DEC belonging to the different pathotypes.
Pathogenic Escherichia coli in Domestic Mammals and Birds
Jacques G. Mainil and John M. Fairbrother
Escherichia coli is an important cause of disease worldwide and occurs in most mammalian species, including humans, and in birds. E. coli was first described in 1885 by a German pediatrician, Theodor Escherich, in the faeces of a child suffering from diarrhoea. In 1893, a Danish veterinarian postulated that the E. coli species comprises different strains, some being pathogens, others not. Today, pathogenic E. coli are classified into categories or pathotypes based on the production of virulence factors and on the clinical manifestations that they cause. The most important categories in animals are those colonising the intestine and causing diarrhoea in calves, pigs, and most other animal species, those colonising the intestine and causing a toxaemia, or oedema disease, in pigs, and those residing in the intestine of healthy animals but capable of invading the host in certain conditions and causing septicaemia in young animals of most species, localised or systemic infections in poultry, or urinary tract infections, especially in dogs. The purpose of this chapter is to give an overview of the most relevant pathotypes causing infections in domestic mammals and birds, with emphasis on their history, virulence-associated properties, economic importance, diagnostic procedures, public health hazard, and vaccine potential.
Genomic Plasticity and the Emergence of New Pathogenic E. coli
Shana R. Leopold, Ulrich Dobrindt, Helge Karch and Alexander Mellmann
Changes at the genomic level of E. coli occur by both on a small scale (e.g. point mutations, insertions, deletions) as well as through lateral gene transfer and homologous recombination of larger fragments. The ability of the E. coli chromosome to incorporate new sequence from various sources, including mobile elements, plasmids, and other exogenous DNA, gives rise to diversity of virulence and adaptative gene content throughout the species. This plasticity of the genome enables E. coli to rapidly adapt, exploiting new niches and forming new pathotypes. Intra-host genome alterations have also been documented, providing models of real time pathogen evolution. We are now learning more about this genomic flexibility as whole genome sequencing becomes more readily available.
Shiga Toxin-encoding Phages: Multifunctional Gene Ferries
Maite Muniesa and Herbert Schmidt
Shiga toxin encoding-bacteriophages (Stx-phages) constitute a heterogeneous group of temperate lambdoid phages that harbor Shiga toxin (stx) genes. The (stx genes are located in the late region of the prophage genome and expression of Stx is under phage control. In their lysogenic state, Stx-phages are incorporated in the bacterial genome at different chromosomal insertion sites. The presence of more than one Stx-phage in the same bacterial genome has implications in the expression of Stx and in the virulence of the respective host strain. Induction of Stx-phages is stimulated by activation of the lytic cycle, either by inducing agents or spontaneously, and this triggers increased production of Stx. Free Stx-phages are found in many environments, therefore being considered as vehicles that mobilize (stx by infection and lysogenization of bacteria in vivo and in vitro. This may lead to the emergence of new bacterial pathogens. Stx-phages can acquire and mobilize foreign genes, including virulence genes present in the chromosome of Escherichia coli strains. The role of Stx-phages in horizontal gene transfer, and their impact on bacterial virulence, have been intensively studied, but their biological impact is not yet completely understood.
Samuel Juillot and Winfried Römer
Shiga toxins are virulence factors produced by Shigella dysenteriae and certain Escherichia coli strains called STEC. The toxins affect target cells already by binding to the plasma membrane through induction of signalling cascades that mainly lead to apoptosis. Furthermore, they inhibit protein biosynthesis by inactivating the 60S subunit of ribosomes. In order to reach their cytoplasmic target, Shiga toxins are endocytosed and transported through the retrograde trafficking pathway towards the endoplasmic reticulum (ER), from where the catalytically active subunit is retro-translocated to the cytosol with the help of ER chaperons and translocon components. Even though Shiga toxins are still a threat to human health, the receptor-binding subunit of Shiga toxins represents a powerful tool to study the mechanisms of intracellular transport and may be exploited as biomedical tool in immunotherapy and tumour imaging.
Escherichia coli Subtilase Cytotoxin: Structure, Function and Role in Disease
Adrienne W. Paton, Hui Wang, Valeria Michelacci, Stefano Morabito and James C. Paton
Subtilase cytotoxin (SubAB) is a recently discovered AB5 toxin family produced by certain strains of pathogenic Escherichia coli, particularly Shiga toxigenic E. coli (STEC) strains that lack the locus of enterocyte effacement (LEE). Its A subunit is a serine protease belonging to the Peptidase_S8 (subtilase) family, while the pentameric B subunit binds to cell surface receptor glycans terminating in the sialic acid N-glycolylneuraminic acid. Receptor binding triggers internalization of the holotoxin and retrograde trafficking to the endoplasmic reticulum (ER), where the A subunit cleaves its only known substrate, the essential Hsp70 family chaperone BiP (GRP78). BiP is a highly conserved master regulator of ER function, which is essential for survival of eukaryotes from simple yeasts to higher organisms such as mammals. Thus, SubAB-mediated BiP cleavage has devastating consequences for the cell, triggering a severe and unresolved ER stress response, ultimately leading to apoptosis. Interestingly, intraperitoneal injection of SubAB is lethal for mice and induces pathological features overlapping those seen in the haemolytic uraemic syndrome, a life-threatening complication of Shiga toxigenic E. coli infection in humans. However, an unequivocal role for SubAB in human disease pathogenesis is yet to be established and carefully designed molecular epidemiological investigations are required to resolve this issue.
Cell Cycle Modulating Toxins Produced by Escherichia coli
István Tóth and Domonkos Sváb
Pathogenic bacteria deploy numerous virulence mechanisms including adhesion/colonization, invasion, overcoming of host defences, and subversion of host cellular functions via/through/by secreted toxins and effectors (Kaper et al., 2004; Pizarro-Cerdá, and Cossart, 2006). Bacterial toxins and effectors that modulate the eukaryotic cell cycle establish a toxin family, termed cyclomodulins (Nougayrède et al., 2005; Oswald et al., 2005). Cyclomodulins are an emerging functional family of toxins that perturb the eukaryotic cell cycle machinery with various mechanisms and determine whether the infected cell will grow and divide or die (Oswald et al., 2005). In E. coli, so far four kinds of cyclomodulins have been identified: the Rho GTPase-activating cytotoxic necrotising factor toxins (CNF) 1 to 3 (Lemonnier et al., 2007), cytolethal lethal distending toxins (CDTs) I to V (Tóth et al., 2009), the cycle-inhibiting factor (Cif; Marchès et al., 2003) and the recently discovered colibactin (Nougayrède et al., 2006). CDTs, Cif, and colibactin block mitosis, while CNFs promote DNA replication without cytokinesis. CDTs and colibactin are genotoxins, while Cif does not cut the double-stranded DNA. Cyclomodulins are encoded by mobile genetic elements including genomic islands (CNF, colibactin, CDT), plasmids (CNF, CDT) and bacteriophages (Cif, CDT). In this review, we summarise the cyclomodulins produced by E. coli.
The Heat Stable and Heat Labile Enterotoxins Produced by ETEC
Sascha Kopic, Ahmad Saleh and John P. Geibel
Enterotoxigenic E. coli (ETEC) produces two toxins: a heat-stable and a heat-labile enterotoxin. Both toxins differ strongly in their structure, their respective receptors and their intracellular mode of action. However, they target common molecular endpoints on the apical membrane of the enterocyte, leading to a intestinal hypersecretion of chloride and a concomitant inhibition of sodium absorption. This chapter will review toxin structure, their receptors and the intracellular processing and signaling involved in toxin exposure. Furthermore, basic principles of intestinal water and ion homeostasis are discussed.
Bernt Eric Uhlin, Jan Oscarsson and Sun Nyunt Wai
As is the case with several other bacterial species, there are strains of E. coli that produce haemolysins. The production may be detected by the use of red blood cells in solid growth media or in other lysis assays. Here we are summarizing findings about properties of three haemolysins/cytolysins: the α-haemolysin (HlyA), the EHEC-Hly and the ClyA (SheA, HlyE) proteins that are found in different E. coli.
Structural, Molecular and Functional Characteristics of Attaching and Effacing Lesions
Ht Law and Julian Andrew Guttman
Pathogenic E. coli infections are major causes of illness and mortality throughout the world. Although many different types of E. coli exist, a subset of these microbes called the attaching and effacing (A/E) pathogens remain extracellular, colonize the intestine, collapse localized microvilli on enterocytes and generate characteristic "lesions" that are hallmarks of the infections. These lesions generate morphological membrane protrusions beneath the attached bacteria that are easily recognizable by microscopy. In this chapter we will examine the structural and molecular components of A/E lesions, highlight recent advances in the field, demonstrate similarities of these structures to those generated by other microbes, and will propose functions for these lesions in the disease process.
Colonization Factor Antigens of ETEC
Felipe Del Canto and Alfredo G. Torres
Enterotoxigenic Escherichia coli (ETEC) cause toxin-mediated diarrhea, which requires that ETEC attaches to epithelial cells using a diverse repertoire of adhesins generically named as colonization factor antigens (CFs). Currently, 22 CFs variants have been identified, displaying different types of structures (fimbriae, fibers and non-fimbrial), which are assembled and displayed at the bacterial surface by three different mechanisms. To date, there is no an effective therapy to prevent ETEC-caused diarrhea and investigators have considered CFs as suitable potential basis of vaccine formulations. In this chapter, we describe the CFs carried by human ETEC strains, addressing structural and functional features as well as their distribution in clinical isolates as determined by epidemiological studies. Furthermore, three non-classical/non-fimbrial ETEC adhesins are described. The information presented here is an overview about human ETEC adherence mechanisms and about how basic and epidemiological research has advanced to obtain crucial data for the design of a therapy to effectively prevent ETEC-caused diarrhea.
Enteroaggregative Escherichia coli and Disease
Nadia Boisen, James P. Nataro and Karen A. Krogfelt
Enteroaggregative Escherichia coli (EAEC) are generally known as causing diarrhea, especially in developing countries and in travelers. Yet, recently it was shown that EAEC is also able to cause urinary tract infections. A recent European outbreak of Shiga toxin-producing EAEC drew the attention and increased the interest on this pathotype. Although the pathogenesis of EAEC is not fully understood, a number of putative virulence factors have been described. The characteristic Aggregative Adherence Fimbriae (AAF) are mucosal adhesins that also elicit inflammatory responses from infected surfaces. EAEC are seen to produce a number of virulence factors including serine protease autotransporter toxins that induce apoptosis of enterocytes. Epidemiologic evidence supports a model of EAEC pathogenesis comprising the concerted action of multiple virulence factors along with induction of inflamation.
Host Cell Invasion by Pathogenic E. coli
Adam J. Lewis, Elizabeth M. Ott, Travis J Wiles and Matthew A. Mulvey
Pathogenic strains of Escherichia coli are likely not the first bacteria that come to mind when most scientists and physicians contemplate invasive microorganisms. Yet, select members of this genetically diverse group of pathogens are adept at invading host cells and taking advantage of the numerous benefits afforded to bacteria within intracellular niches. These benefits include access to alternate nutrient sources and increased protection from the shear flow of bodily fluids and the damaging effects of host phagocytes, complement, antimicrobial peptides, antibodies, and, in some cases, antibiotics. To reap these rewards, bacterial pathogens must manipulate host cell machinery to promote their uptake, subsequently avoid destruction within lysosomal compartments, and ultimately return to the extracellular environment to perpetuate their genetic lineage. Here we cover four invasive pathotypes of E. coli: uropathogenic E. coli (UPEC), neonatal meningitis E. coli (NMEC), enteroinvasive E. coli (EIEC), and adherent-invasive E. coli (AIEC). The molecular mechanisms and consequences of host cell invasion by these important pathogens are discussed, with an emphasis on UPEC.
Vaccines Against Enteric E. coli Infections in Animals
Eric Cox, Vesna Melkebeek, Bert Devriendt, Bruno M. Goddeeris and Daisy Vanrompay
Several E. coli animal pathogens exist, which have an important economical impact, such as enterotoxigenic E. coli, avian pathogenic E. coli and mammary pathogenic E. coli. Furthermore, ruminants are carrier of enterohemorrhagic E. coli, which are not pathogenic for them, but can be transmitted to humans via direct contact and contamination of food or drinks, resulting in severe disease. Nevertheless, only few E. coli vaccines are available. This chapter summarizes the current status of vaccines for preventing intestinal E. coli infections in animals and will deal with vaccines against ETEC infections in pigs and ruminants and vaccines, which prevent EHEC colonization in cattle.
Perspective of Use of Vaccines for Preventing Enterotoxigenic Escherichia coli (ETEC) Diarrhoea in Humans
Enterotoxigenic Escherichia coli (ETEC) strains are the leading bacteria that cause diarrhea to young children living in the developing countries and children and adults traveling to these areas. ETEC strains produce adhesins that mediate bacteria initial attachment to host epithelial cells and subsequent colonization at host small intestines, and enterotoxins including heat-labile toxin (LT) and heat-stable toxin (STa) that disrupt fluid homeostasis in host epithelial cells to cause electrolyte-rich fluid hyper-secretion and diarrhea. As country-wide implementation of clean drinking water and effective sanitation systems, which can effectively limit ETEC infections, are still an out of reach goal in many developing countries, vaccination is the most practical prevention approach. Vaccines inducing host anti-adhesin immunity to block ETEC attachment and colonization and also antitoxin immunity to neutralize enterotoxicity are considered optimal against ETEC diarrhea. However, although a cholera vaccine (Dukoral®) that stimulates anti-CT immunity provides short-term cross protection against ETEC diarrhea for travelers, vaccines effectively protecting against ETEC are currently still lacking. Vaccines under development are whole-cell oral vaccines and intend to stimulate intestinal mucosal immunity, and newer experimental ETEC vaccine candidates are aimed to provide long lasting and more broad-based protection.
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(EAN: 9781908230379 Subjects: [microbiology] [bacteriology] [molecular microbiology] [genomics] )