Pathogenesis of Bacterial Infections in Animals: Gyles/Pathogenesis of Bacterial Infections in Animals
معرفی کتاب «Pathogenesis of Bacterial Infections in Animals: Gyles/Pathogenesis of Bacterial Infections in Animals» نوشتهٔ Gyles, Carlton L. (editor);Prescott, John F. (editor);Songer, J. Glenn (editor);Thoen, Charles O. (editor)، منتشرشده توسط نشر Wiley-Blackwell در سال 2010. این کتاب در فرمت pdf، زبان انگلیسی ارائه شده است.
CHAPTER 1
Themes in Bacterial Pathogenic Mechanisms
C. L. Gyles and J. F. Prescott
INTRODUCTION
The speed of progression of our understanding of pathogenic bacteria and their interactions with the host at the molecular level is providing novel insights and perspectives on pathogens and pathogenicity at an almost overwhelming rate. Such information and insights are of fundamental value in designing better and unprecedented ways to counter infectious diseases. For example, studies on the use of drugs that jam quorum sensing communication systems have shown promise that this approach may be an effective method of preventing virulence regulons from being activated (Hentzer et al. 2003; Rasko et al. 2008). In a recent study, Rasko et al. (2008) identified a novel compound (LED209) that blocks the bacterial histidine sensor kinase, QseC, which is found in several gram-negative bacterial pathogens and is required for expression of certain virulence genes. These authors have shown that LED209 is nontoxic to mice and protected mice against death due to Salmonella Typhimurium or Francisella tularensis. Rasko and coworkers (2008) have noted that, unlike antibiotics, this anti-virulence approach does not threaten the life of the bacteria and may therefore not exert a selective pressure that selects for resistant organisms. However, if this method is a threat to a critical niche for these bacteria, it could also have a selective effect.
Although an overview of the basic themes in bacterial pathogenic mechanisms provides a conceptual skeleton for the extensive details of individual pathogens given in later chapters, understanding of virulence and pathogenicity is changing rapidly. The fundamental concepts have withstood the test of time fairly well, but new knowledge has brought the complexities of hostpathogen interactions into sharper focus and has identified nuances that had not been recognized previously (Finlay and Falkow 1997; Bhavsar et al. 2007). Although more is understood about bacteria, especially through the application of genome sequencing and related technologies, bacterial infections seem to be increasing and changing, in particular those associated with increased antibiotic resistance, driven by exposure to more powerful antibiotics. Numerous anthropogenic activities including antibiotic use at both therapeutic and subtherapeutic concentrations may be driving bacterial evolution and the selection of pathogens adapted to changed circumstances (Chopra et al. 2003; Davies et al. 2006). Against the background of stunning advances in technologies, there is increasing recognition of the poor general application of well-established simple infection control techniques such as hand-washing to reduce the burden of infection in people and in animals in clinical settings. The fight against bacterial infections requires constant vigilance and disciplined use of hard-earned knowledge, not simply the application of new technology.
BASIC STEPS IN PATHOGENESIS CONTINUE TO PROVIDE A SOUND FOUNDATION
The basic steps in the establishment of infection by a bacterial pathogen are:
1. attachment or other means of entry into the body;
2. evasion of normal host defenses against infection;
3. multiplication to significant numbers at the site of infection and/or spread to other sites;
4. damage to the host, either directly or through the nonspecific or specific immune host response to the bacterium;
5. transmission from the infected animal to other susceptible animals, so that the infection cycle can continue.
As would be expected for carefully regulated systems, the infection process is a dynamic continuum rather than a clear series of steps, but breaking it down into progressive steps allows ease of understanding.
Pathogen Association with the Host
Successful colonization of the skin or a mucosal surface of the host is usually the first prerequisite of the infectious process. Some organisms need to employ motility and chemotaxis as well as resistance to acid and bile in order to reach their target host cells. Initial contact between bacterial pathogen and host cell is usually mediated by fimbrial or nonfimbrial adhesins on the bacterial surface (Kline et al. 2009). Binding may result either in extracellular colonization or in internalization of the pathogen. The adhesins bind to specific host cell surface receptors, and both host and organ specificity of infection may be determined by differences among animals in cellular, receptors for the bacterial adhesins. For example, the Listeria monocytogenes adhesion molecule internalin A (InlA) promotes uptake of the bacterium into intestinal epithelial cells by binding to E-cadherin. InlA binds to human and rabbit E-cadherin and causes disease in these species; however, it fails to bind to mouse E-cadherin and so does not cause disease in mice. Interestingly, Wollert et al. (2007) recently showed that by making two substitutions in InlA they could increase the binding affinity to mouse E-cadherin by 10,000-fold and thereby establish experimental infection in mice. The researchers noted that newly emerging diseases may arise by similar naturally occurring mutations.
As many receptors are developmentally regulated, age specificity may also be determined by the receptor to which a pathogen binds. This is seen in K99 (F5) pili of porcine and bovine enterotoxigenic Escherichia coli (ETEC), which bind to the intestinal epithelium of neonatal animals, and in F18 pili of porcine ETEC, which bind to the intestinal epithelium of recently weaned pigs.
Bacterial pathogens, including those associated with wound infections, may bind to extracellular matrix molecules such as fibronectin, collagen, laminin, or other proteins possessing RGD (ArgGly-Asp) sequences for binding of eukaryotic cell membrane integrins. Bacteria may use "invasins" to mediate their uptake into nonprofessional phagocytic host cells after attaching to molecules on the cell surface and activating host cell signaling to facilitate their entry, often through host cell cytoskeletal rearrangement (Galn and Cossart 2005). An excellent example of this is found in the adherence to and invasion of M cells by Yersinia enterocolitica and Y. pseudotuberculosis. The outer membrane protein invasin produced by these bacteria binds to β1 integrin on the surface of M cells and triggers uptake of the bacteria in a zipper-like internalization process (Hauck 2002). This entry provides the bacteria with access to the lymphoid tissue below, and to draining lymph nodes, in which the bacteria are well equipped to multiply.
Facultative intracellular pathogens may deliberately target macrophages, for example by entering through complement- or other lectin-binding receptors and thus avoiding the oxidative burst that might otherwise kill them. Remarkably and, at first sight, paradoxically, the safest place in the body for these organisms, which subsequently interfere with normal macrophage phagosome maturation, is actually a macrophage.
Pathogen Multiplication and Evasion of Host Defenses
After initial association with the host, bacterial pathogens need to evade host defenses and to multiply to numbers sufficient for the infection to be self-sustaining rather than to be aborted by the host response. The "defensins" involved in the evasion multiplication process can be divided into those involved in defense against innate immune mechanisms and those involved in defense against specific immune mechanisms.
Innate immunity can be overcome in a wide variety of ways (discussed throughout the book, in particular Chapter 2). The lack of available iron that restricts the growth of many bacteria within the body is an important defense mechanism as iron is critical for iron-containing cofactors for enzymes required for primary and secondary bacterial metabolism. This limitation is often overcome by the iron-acquisition systems of pathogens. Recognition of the importance of iron acquisition by pathogens has led to a recent focus on inhibiting siderophores in the development of novel antibacterials (Miethke and Marahiel 2007). This is part of an approach that recognizes that inhibition of bacterial growth alone as a screening approach to antibacterial-drug discovery will result in numerous potential important pathogen targets being missed (Davies et al. 2006).
Many organisms, particularly those that cause septicemia and pneumonia, have prominent, usually carbohydrate, capsules that help the organism resist phagocytosis in the absence of antibodies. Some capsules mimic host matrices so that the organisms are unrecognized by phagocytes. The lipopolysaccharide molecules of some gram-negative bacteria can protect them from the membrane attack complex of complement or from the insertion of antimicrobial peptides. Some bacteria such as streptococci can break down complement components through C5a peptidase or other proteases. Other bacteria may destroy or impair phagocytic cells through their leukocidins such as the RTX (repeats in the structural toxin) toxins, or enable bacteria to survive inside phagocytes through enzymes such as superoxide dismutases or catalases.
Acquired immunity can be overcome in several ways. These include the ability to degrade immunoglobulins with enzymes such as the IgA proteases of Histophilus somni, or the ability to alter the antigenicity of cell surface components such as fimbriae or outer membrane proteins. Bacterial superantigens can dramatically up-regulate certain T cell subsets with specific V regions, which may result not only in a "cytokine storm," which confuses the immune system, but also in the deletion of these cells from the immune repertoire. In ways that are not well understood, some bacteria, such as Rhodococcus equi, may modulate the cytokine response to infection so that an ineffective Th2 rather than effective Th1-based immune response leads to development of disease. The role of "modulins" in diverting the host immune response is far less well understood for bacteria than for viral infections.
Pathogen Damage to the Host
Bacterial damage to the host is usually essential for immediate or long-term acquisition of the nutrients that the bacterium needs to thrive and to continue its pathogenic lifestyle. Infection does not always lead to disease, which is only one of the possible outcomes of bacteria–host interaction. Other outcomes include commensalism and latency.
Among the wide variety of "offensins" produced by bacteria are many different types of toxins. Toxins can be classified in different and not fully satisfactory ways, although that based on activity is the most logical (Wilson et al. 2002). Type I toxins, the membrane-acting toxins, bind to cell surface receptors to transduce a signal that results in the activation of host cell pathways, leading to aberrant cell metabolism. Examples in E. coli include the heat-stable enterotoxin a STa, which binds to the receptor for guanylyl cyclase, resulting in hypersecretion due to excessive levels of cyclic guanosine monophosphate (cGMP), and the cytotoxic necrotizing factor (CNF) toxins, which activate Rho guanosine triphosphatases (GTPases), resulting in cytoskeletal rearrangements. Other examples include the Bacillus anthracis edema factor (EF), the Pasteurella multocida toxin (PMT), and the exoenzyme S (ExoS) toxin of Pseudomonas aeruginosa. The superantigens fall into this class. Type II toxins, the membrane-damaging toxins, include the membrane channel-forming toxins using the β-barrel structure (e.g., Staphylococcus aureus α-toxin), channel-forming toxins involving α-helix formation, the large range of thiol-activated cholesterol-binding cytolysins, and the RTX toxins. Type II toxins that damage membranes enzymatically include the phospholipases of many bacteria. Type III toxins, the intracellular toxins, are toxins that enter and are active within the cell. These are often active-binding (AB) two-component toxin molecules. Examples include the adenosine diphosphate (ADP)-ribosyl transferasesf (e.g., the E. coli heat-labile enterotoxin [LT]), the N-glycosidases (e.g., the Shiga toxins), the adenylate cyclases (e.g., the Bordetella bronchiseptica adenylate cyclase toxin), and the metalloendoproteases of the clostridial neurotoxins.
Tissue damage and impairment of host function is often due to the inflammatory response mounted by the host in response to infection with a bacterial pathogen. Sepsis represents an extreme case in which hyperresponsiveness to lipopolysaccharide (LPS) and/or other host signaling molecules unleashes an excessively strong inflammatory response resulting in vascular damage, hypotension, and multiple organ damage. The inflammatory response mounted by the host may also provide a point of entry for certain invasive enteric pathogens, such as Shigella dysenteriae. This organism carries a virulence plasmid-encoded homologue of the msbB gene in addition to the chromosomal copy, and it has been suggested that this may ensure complete acylation of lipid A and production of highly stimulatory LPS. The massive leukocyte infiltration between epithelial cells promotes invasion by the pathogens (D'Hauteville et al. 2002).Asimilar arrangement for the msbB gene exists in E. coli O157:H7.
Pathogen Transmission from the Host
Although not often considered in a discussion of bacterial pathogenesis, a crucial feature of bacterial pathogens is their ability to use their pathogenic nature to ensure their further transmission from the host, either back into their environmental reservoir or directly to other susceptible hosts. Depending on the infection, further transmission to animals may be immediate or may even involve decades.
An important aspect of transmission involves bacterial infections of animals that are important primarily because of the transmission of organisms from animals to humans. In some cases, as with Shiga toxin-producing E. coli (STEC) O157:H7, the bacteria are normal flora in the intestine of animals, where they do not cause disease; however, they do induce severe disease following transmission to humans. Asimilar situation exists for Campylobacter jejuni and most serotypes of Salmonella in poultry. Efficient transfer from their reservoir hosts to their accidental host occurs directly through contamination of foods of animal origin and indirectly through fecal contamination of water and the environment.
CONCEPTS OF VIRULENCE ARE BEING REFINED
Bacteria cause disease by a variety of virulence mechanisms in a highly complex process that usually involves penetrating the host's protective barriers, evading deeper host defenses, multiplying to significant numbers, and damaging the host, leading to escape from the host to continue the cycle. Although this concept of virulence is well established, the resurgence or emergence of infectious diseases in humans in recent years because of changes in host susceptibility (AIDS, immunosuppressive drugs, hospital-acquired infections) emphasizes the importance of host factors in determining the outcome of encounters with microbes. Many people now die in hospitals from infectious agents that are not pathogens in healthy people. A parallel situation exists in many small animal hospitals, especially in intensive care units. Similarly, the ability of some bacteria rapidly to develop or acquire antimicrobial resistance and then to emerge as significant problems in hospital or community settings emphasizes the importance of environmental factors in determining the outcome of infection. Virulence does not occur in a vacuum; it is contextually dependent. In this case, antibiotic use in hospitals may remove the inhibitory effects of the normal microbial flora in reducing colonization by exogenous, resistant, bacteria. Furthermore, bacterial pathogens themselves may carry genes for bacteriocins that are sometimes linked to virulence genes or bacteriophages that possess virulence genes, which are an important part of their success as pathogens. Selective pressures other than just interaction with the host may exert profound influence on the evolution of pathogens (Brown et al. 2006).
(Continues...) Excerpted from Pathogenesis of Bacterial Infections in Animals by Carlton L. Gyles, J.F. Prescott, Glenn Songer, Charles O. Thoen. Copyright © 2010 John Wiley & Sons, Ltd. Excerpted by permission of John Wiley & Sons.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site. Front Matter Colour Plates Themes in Bacterial Pathogenic Mechanisms / C L Gyles, J F Prescott Subversion of the Immune Response by Bacterial Pathogens / D C Hodgins, P E Shewen Evolution of Bacterial Virulence / P Boerlin Streptococcus / J F Timoney Staphylococcus / K Hermans, L A Devriese, F Haesebrouck Bacillus Anthracis / J Mogridge, S Shadomy, P Turnbull Mycobacterium / I Olsen, R G Barletta, C O Thoen and / R Moore, A Miyoshi, L G C Pacheco, N Seyffert, V Azevedo Rhodococcus / J F Prescott, W G Meijer, J A V̀zquez-Boland Listeria / C J Czuprynski, S Kathariou, K Poulsen Neurotoxigenic Clostridia / H Ḇhnel, F Gessler Histotoxic Clostridia / J Glenn Songer Enteric Clostridia / J Glenn Songer Salmonella / P A Barrow, M A Jones, N Thomson Escherichia Coli / C L Gyles, J M Fairbrother Yersinia / M A Bergman, R Chafel, J Mecsas Pasteurella / J D Boyce, M Harper, I W Wilkie, B Adler Mannheimia / R Y C Lo Actinobacillus / J I MacInnes Haemophilus / I Sandal, L B Corbeil, T J Inzana Bordetella / K Register, E Harvill Brucella / S C Olsen, B H Bellaire, R M Roop, C O Thoen Pseudomonas / E L Westman, J M Matewish, J S Lam Moraxella / J A Angelos and / L A Joens, F Haesebrouck, F Pasmans Lawsonia Intracellularis / C J Gebhart, R M C Guedes Gram-Negative Anaerobes / D J Hampson, T G Nagaraja, R M Kennan, J I Rood Leptospira / B Adler, A de la Pęa Moctezuma Mycoplasma / G F Browning, M S Marenda, P F Markham, A H Noormohammadi, K G Whithear Chlamydia / A Pospischil, N Borel, A A Andersen Rickettsiales / T Waner, S Mahan, P Kelly, S Harrus Index.
This much-anticipated third edition again consolidates the knowledge of more than twenty experts on pathogenesis of animal disease caused by various species or groups of bacteria. Emphasizing pathogenic events at the molecular and cellular levels, the editors and contributors place these developments in the context of the overall picture of disease. Pathogenesis of Bacterial Infections in Animals, Third edition, updates and expands the content of the second edition and includes cutting-edge information from the most current research.
Comments on previous editions:
"...highly recommended."
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"...recommended for graduate students and specialists in microbiology, pathology and infectious disease."
—U.S. Animal Health Association Newsletter
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