Comprehensive review of the major bacterial pathogens of animals, focusing on the current understanding of how they cause disease Pathogenesis of Bacterial Infections in Animals, Fifth Edition is a specialist reference that provides a comprehensive review of bacterial pathogens in animals and their complex interplay with disease processes, offering a complete understanding of how bacteria cause disease in animals. It covers the many recent advances in the field including the newest taxonomies. In this revised and long anticipated fifth edition, additional introductory chapters have been added to set the material in context, and more figures added to integrate and improve understanding and comprehension throughout the text. A companion website presents the figures from the book in PowerPoint and references. This detailed reference includes novel approaches to controlling bacterial pathogens in the light of growing concerns about antimicrobial resistance, with more than 70 expert authors sharing their wisdom on the topic. While molecular pathogenesis is a major aspect in almost every chapter, the authors have been careful to place pathogens in their broader context. Pathogenesis of Bacterial Infections in Animals, Fifth Edition also contains information on: Themes in bacterial pathogenesis, covering the basic elements of pathogenesis, concepts of virulence, host-pathogen interactions and communication, and pathogenesis in the post-genomic era Evolution of bacterial pathogens, covering what they are and how they emerge, along with sources of genetic diversity, population structure, and genome plasticity Understanding of pathogenesis through pathogenomics and bioinformatics, including how mutations generate pathogen diversity, and an overview of genome sequencing technologies Subversion of the immune response by bacterial pathogens, covering subversion of both innate responses and adaptive immunity Pathogenesis of Bacterial Infections in Animals, Fifth Edition is an essential resource for graduate students in veterinary medicine and animal science, and for veterinary microbiologists, pathologists, infectious disease experts, and others interested in bacterial disease. It is the only book to cover this topic to this depth through the wealth of insight of dozens of qualified and practicing professionals. About the Author John F. Prescott is University Professor Emeritus at the University of Guelph, in Guelph, Ontario, Canada.
The respiratory system is well defended against inhaled bacteria by a dynamic system of interacting layers, including mucociliary clearance, host defense factors including antimicrobial peptides in the epithelial lining fluid, proinflammatory responses of the respiratory epithelium, resident alveolar macrophages, and recruited neutrophils and monocytes. Nevertheless, these manifold defenses are susceptible to failure as a result of stress, glucocorticoids, viral infections, abrupt exposure to cold air, and poor air quality. When some of these defenses fail, the lung can be colonized by bacterial pathogens that are equipped to evade the remaining defenses, resulting in the development of pneumonia. This review considers the mechanisms by which these predisposing factors compromise the defenses of the lung, with a focus on the development of bacterial pneumonia in cattle and supplemented with advances based on mouse models and the study of human disease. Deepening our understanding of how the respiratory defenses fail is expected to lead to interventions that restore these dynamic immune responses and prevent disease.
This article reviews the roles that laterally transferred genes (LTG) play in the virulence of bacterial pathogens. The features of LTG that allow them to be recognized in bacterial genomes are described, and the mechanisms by which LTG are transferred between and within bacteria are reviewed. Genes on plasmids, integrative and conjugative elements, prophages, and pathogenicity islands are highlighted. Virulence genes that are frequently laterally transferred include genes for bacterial adherence to host cells, type 3 secretion systems, toxins, iron acquisition, and antimicrobial resistance. The specific roles of LTG in pathogenesis are illustrated by specific reference to Escherichia coli, Salmonella, pyogenic streptococci, and Clostridium perfringens.
Many gram-positive bacteria covalently tether their surface adhesins to the cell wall peptidoglycan. We find that surface proteins of Staphylococcus aureus are linked to the cell wall by sortase, an enzyme that cleaves polypeptides at a conserved LPXTG motif. S. aureus mutants lacking sortase fail to process and display surface proteins and are defective in the establishment of infections. Thus, the cell wall envelope of gram-positive bacteria represents a surface organelle responsible for interactions with the host environment during the pathogenesis of bacterial infections.
Enteroinvasive E. coli (EIEC). EIEC are biochemically, genetically and pathogenically closely related to Shigella spp. Numerous studies have shown that Shigella and E. coli are taxonomically indistinguishable at the species level73,74, but, owing to the clinical significance of Shigella, a nomenclature distinction is still maintained. The four Shigella species that are responsible for human disease, S. dysenteriae, S. flexneri, Shigella sonnei and Shigella boydii, cause varying degrees of dysentery, which is characterized by fever, abdominal cramps and diarrhoea containing blood and mucous. EIEC might cause an invasive inflammatory colitis, and occasionally dysentery, but in most cases EIEC elicits watery diarrhoea that is indistinguishable from that due to infection by other E. coli pathogens2. EIEC are distinguished from Shigella by a few minor biochemical tests, but these pathotypes share essential virulence factors. EIEC infection is thought to represent an inflammatory colitis, although many patients seem to manifest secretory, small bowel syndrome. The early phase of EIEC/Shigella pathogenesis comprises epithelial cell penetration, followed by lysis of the endocytic vacuole, intracellular multiplication, directional movement through the cytoplasm and extension into adjacent epithelial cells (reviewed in Ref. 75). Movement within the cytoplasm is mediated by nucleation of cellular actin into a 'tail' that extends from one pole of the bacterium. In addition to invasion into and dissemination within epithelial cells, Shigella (and presumably EIEC) also induces apoptosis in infected macrophages76. Genes that are required to effect this complex pathogenetic scheme are present on a large virulence plasmid that is found in EIEC and all Shigella species. The sequence of the 213-kb virulence plasmid of S. flexneri (pWR100) indicates that this plasmid is a mosaic that includes genetic elements that were initially carried by four plasmids77. One-third of the plasmid is composed of insertion sequence (IS) elements, which are undoubtedly important in the evolution of the virulence plasmid. This plasmid encodes a type III secretion system (see below) and a 120-kDa outer-membrane protein called IcsA, which nucleates actin by the binding of N-WASP8,78. The growth of actin micofilaments at only one bacterial pole induces movement of the organism through the epithelial cell cytoplasm. This movement culminates in the formation of cellular protrusions that are engulfed by neighbouring cells, after which the process is repeated. Although EIEC are invasive, dissemination of the organism past the submucosa is rare.
Much of EIEC/Shigella pathogenesis seems to be the result of the multiple effects of its plasmid-borne type III secretion system. This type III secretion system secretes multiple proteins, such as IpaA, IpaB, IpaC and IpgD, which mediate epithelial signalling events, cytoskeletal rearrangements, cellular uptake, lysis of the endocytic vacuole and other actions (reviewed in Refs 79,80). The type III secretion system apparatus, which is encoded by mxi and spa genes, enables the insertion of a pore containing IpaB and IpaC proteins into host cell membranes. In addition to pore formation, IpaB has several functions, such as binding to the signalling protein CD44, thereby triggering cytoskeletal rearrangements and cell entry, and binding to the macrophage caspase 1, resulting in apoptosis and release of IL-1 from macrophages. IpaC induces actin polymerization, which leads to the formation of cell extensions by activating the GTPases Cdc42 and Rac. The actin polymerization activity resides in the carboxy terminus of IpaC, whereas the amino terminus of this protein is involved in lamellipodial extensions. Conversely, IpaA binds to vinculin and induces actin depolymerization, thereby helping to organize the extensions that are induced by IpaC into a structure that enables bacterial entry. The translocated effector protein IpgD is a potent inositol 4-phosphatase that helps to reorganize host-cell morphology by uncoupling the cellular plasma membrane from the actin cytoskeleton, which leads to membrane blebbing81. Although the extensively characterized type III secretion system is essential for the invasiveness characteristic of EIEC and Shigella species, additional virulence factors have been described, including the plasmid-encoded serine protease SepA, the chromosomally encoded aerobactin iron-acquisition system and other secreted proteases that are encoded by genes present on pathogenicity islands (see below).
Regulation of virulence factor expression by physical DNA rearrangements is uncommon in pathogenic E. coli but phase variation is seen with type 1 fimbriae. Transcription of the fim operon that encodes type 1 fimbriae is primarily under the control of an invertible element that contains the promoter responsible for transcription of the main structural subunit. Individual bacterial cells either express the fimbriae over their entire surface or do not express any fimbriae. This phase variation of type 1 fimbriae is controlled at the transcriptional level by the invertible element, which is regulated by the FimB and FimE recombinases146. The inversion seems to be regulated during the course of infection, and the orientation of the element correlates with whether UPEC strains remain localized to the bladder. In cystitis infections most of the strains have the invertible element in the 'on' position and express type 1 fimbriae, whereas when they leave the bladder and ascend to the kidneys to cause pyelonephritis, most of the strains have the element in the 'off' position and do not express type 1 fimbriae95. The regulation of type 1 fimbriae in UPEC is further complicated by cross-talk between two different adhesion operons, whereby PapB, a key regulator of the pap operon, inhibits type 1 phase variation141. 59ce067264