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Pathogenesis of Bacterial Infections in Animals, Fourth Edition captures the rapid developments in understanding the mechanisms of virulence of the major bacterial pathogens of animals. Now including a color plate section, the book presents an overview of pathogenesis, including relevant events that occur in the herd or flock and its environment, and activities that take place at the cellular and molecular levels. With contributions from 64 experts in the field, this book serves as a great reference for graduate students in veterinary medicine and animal science, microbiologists, virologists and pathologists.

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Contents

Preface

Contributors

1 Themes in Bacterial Pathogenic Mechanisms

INTRODUCTION

BASIC STEPS IN PATHOGENESIS CONTINUE TO PROVIDE A SOUND FOUNDATION

CONCEPTS OF VIRULENCE ARE BEING REFINED

HOST-BACTERIA COMMUNICATION IS CRITICAL

PATHOGENESIS IN THE POST-GENOMIC ERA

EVOLUTION OF PATHOGENS— THE PATH TRAVELED MAY PROVIDE INSIGHTS INTO THE ROAD AHEAD

REFERENCES

2 Subversion of the Immune Response by Bacterial Pathogens

INTRODUCTION

SUBVERSION OF INNATE IMMUNE RESPONSES

SUBVERSION OF ADAPTIVE IMMUNITY

CONCLUSION

REFERENCES

3 Evolution of Bacterial Virulence

WHAT ARE PATHOGENS AND HOW DO THEY EMERGE?

BACTERIAL FITNESS AND VIRULENCE

SOURCES OF GENETIC DIVERSITY, POPULATION STRUCTURE, AND GENOME PLASTICITY

PATHOGENICITY ISLANDS

BACTERIOPHAGES AND THEIR ROLE IN PATHOGEN EVOLUTION AND VIRULENCE

ILLUSTRATIONS OF VIRULENCE EVOLUTION

CONCLUSION

REFERENCES

4 Streptococcus

INTRODUCTION

STREPTOCOCCUS AGALACTIAE

STREPTOCOCCUS DYSGALACTIAE

STREPTOCOCCUS UBERIS

STREPTOCOCCUS EQUI

STREPTOCOCCUS ZOOEPIDEMICUS

STREPTOCOCCUS CANIS

STREPTOCOCCUS PORCINUS

STREPTOCOCCUS SUIS

STREPTOCOCCUS PNEUMONIAE

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

REFERENCES

5 Staphylococcus

INTRODUCTION

CHARACTERISTICS OF THE ORGANISM

PATHOGENIC STAPHYLOCOCCUS SPECIES

SOURCES OF THE BACTERIUM

BACTERIAL VIRULENCE FACTORS

PATHOGENESIS

TYPES OF DISEASE AND PATHOLOGIC CHANGES

INTERACTIONS BETWEEN THE BACTERIUM AND HOST DEFENSES

IMMUNITY AND ITS IMPACT ON PATHOGENESIS

CONCLUSIONS: NEW DEVELOPMENTS

REFERENCES

6 Bacillus anthracis

INTRODUCTION

ETIOLOGY, ECOLOGY, AND EPIDEMIOLOGY

SYMPTOMATOLOGY AND DIAGNOSIS

BACTERIOLOGY

PATHOGENESIS

IMMUNOLOGY

CONTROL

FUTURE DIRECTIONS

REFERENCES

7 Mycobacterium

INTRODUCTION

CHARACTERISTICS AND SOURCES OF THE ORGANISMS

BACTERIAL VIRULENCE FACTORS

PATHOGENESIS

IMMUNITY

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

REFERENCES

8 Corynebacterium and Arcanobacterium

CORYNEBACTERIUM

CORYNEBACTERIUM PSEUDOTUBERCULOSIS

OTHER CORYNEBACTERIA

ARCANOBACTERIUM

ARCANOBACTERIUM PYOGENES

FUTURE DIRECTIONS

REFERENCES

9 Rhodococcus

INTRODUCTION

CHARACTERISTICS AND SOURCES OF THE ORGANISM

BACTERIAL VIRULENCE FACTORS

PATHOGENESIS

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

REFERENCES

10 Listeria

INTRODUCTION

CHARACTERISTICS

SOURCES OF INFECTION

VIRULENCEFACTORS

PATHOGENESIS

HOST-PATHOGEN INTERACTIONS IN LISTERIOSIS

PREVENTION AND TREATMENT

CONCLUSION

11 Neurotoxigenic Clostridia

INTRODUCTION

CLOSTRIDIUM TETANI AND CLOSTRIDIUM BOTULINUM

TOXINS

TETANUS

BOTULISM

CONTROL AND PREVENTION

BoNT AS THERAPEUTICS

CONCLUSIONS

REFERENCES

12 Histotoxic Clostridia

INTRODUCTION

VIRULENCE FACTORS AND PATHOGENESIS

CLOSTRIDIUM PERFRINGENS

CLOSTRIDIUM SEPTICUM

CLOSTRIDIUM CHAUVOEI

CLOSTRIDIUM NOVYI

CLOSTRIDIUM SORDELLII

CONCLUSION

REFERENCES

13 Enteric Clostridia

INTRODUCTION

CLOSTRIDIUM PERFRINGENS

CLOSTRIDIUM DIFFICILE

CLOSTRIDIUM SEPTICUM

CLOSTRIDIUM SPIROFORME

CLOSTRIDIUM PILIFORME

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

REFERENCES

14 Salmonella

INTRODUCTION

SALMONELLA INFECTIONS OF CATTLE

SALMONELLA INFECTIONS OF SHEEP

SALMONELLA INFECTIONS OF PIGS

INFECTIONS OF DOMESTIC FOWL AND OTHER AVIAN SPECIES

COLONIZATION OF THE INTESTINE

SALMONELLA INVASION AND ENTEROPATHOGENESIS

SYSTEMIC DISEASE

GENOME STRUCTURE WITH REFERENCE TO VIRULENCE

IMMUNITY TO INFECTION AND ITS MANIPULATION BY SALMONELLA

CONCLUSION—PROBLEMS AND OPPORTUNITIES

REFERENCES

15 Escherichia coli

INTRODUCTION

TYPES OF ESCHERICHIA COLI IMPLICATED IN DISEASE

ETEC

PATHOGENESIS OF ETEC

STEC

EPEC

Ex PEC

IMMUNITY

CONCLUSIONS

REFERENCES

16 Yersinia

INTRODUCTION

CLASSIFICATION OF YERSINIA SPECIES

SOURCES OF YERSINIA SPECIES

VIRULENCE FACTORS

PATHOGENESIS

VACCINES

FUTURE DIRECTIONS

REFERENCES

17 Pasteurella

INTRODUCTION

CHARACTERISTICS AND SOURCES OF THE ORGANISMS

DISEASES CAUSED BY PASTEURELLA MULTOCIDA

PASTEURELLA MULTOCIDA: BACTERIAL VIRULENCE FACTORS

PMT

LPS

PATHOGENESIS

IMMUNITY IN PASTEURELLA MULTOCIDA INFECTIONS

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

ACKNOWLEDGMENT

REFERENCES

18 Mannheimia

INTRODUCTION

CHARACTERISTICS AND SOURCES OF MANNHEIMIA

BACTERIAL VIRULENCE FACTORS

PATHOGENESIS AND DISEASE

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

ACKNOWLEDGMENTS

REFERENCES

19 Actinobacillus

ACTINOBACILLUS PLEUROPNEUMONIAE

ACTINOBACILLUS LIGNIERESII

ACTINOBACILLUS EQUULI

ACTINOBACILLUS SUIS

FUTURE PROSPECTS

REFERENCES

20 Haemophilus

INTRODUCTION

CHARACTERISTICS

HABITAT AND TRANSMISSION

HISTOPHILUS SOMNI

HAEMOPHILUS PARASUIS

AVIBACTERIUM PARAGALLINARUM

CONCLUSIONS

REFERENCES

21 Bordetella

INTRODUCTION

CHARACTERISTICS OF THE GENUS

SOURCES OF THE BACTERIA

VIRULENCE FACTORS

PATHOGENESIS

CONCLUSION

REFERENCES

22 Brucella

INTRODUCTION

CHARACTERISTICS AND SOURCES OF THE ORGANISMS

BACTERIAL VIRULENCE FACTORS

PATHOGENESIS

DISEASE CONTROL AND EPIDEMIOLOGY

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

REFERENCES

23 Pseudomonas

INTRODUCTION

DISEASES

OVERVIEW OF PATHOGENESIS

VIRULENCE FACTORS OF PSEUDOMONAS AERUGINOSA

ANTIBIOTIC RESISTANCE

IMPACT OF WHOLE GENOME SEQUENCES

VACCINES

CONCLUSIONS AND FUTURE PROSPECTS

REFERENCES

24 Moraxella

INTRODUCTION

INFECTIOUS BOVINE KERATOCONJUNCTIVITIS

PATHOGENESIS OF MORAXELLA BOVIS

CONCLUSIONS

REFERENCES

25 Campylobacter and Helicobacter

CAMPYLOBACTER

HELICOBACTER

GASTRIC HELICOBACTERS

ENTEROHEPATIC HELICOBACTERS

PATHOGENESIS AND VIRULENCE FACTORS

CONCLUSIONS

REFERENCES

26 Lawsonia intracellularis

CHARACTERISTICS OF LAWSONIA INTRACELLULARIS

SOURCES OF LAWSONIA INTRACELLULARIS

VIRULENCE FACTORS

PATHOGENESIS

CONCLUSION

REFERENCES

27 Gram-negative Anaerobes

INTRODUCTION

GENERAL BACTERIAL VIRULENCE FACTORS

FUSOBACTERIUM

BACTEROIDES

PREVOTELLA AND PORPHYROMONAS

DICHELOBACTER

TREPONEMA

BRACHYSPIRA

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

REFERENCES

28 Leptospira

LEPTOSPIRA—THE BASICS

LEPTOSPIROSIS—THE DISEASE

GENOMICS, PROTEOMICS, AND MOLECULAR BIOLOGY

PATHOGENESIS OF LEPTOSPIROSIS

MECHANISMS OF IMMUNITY IN LEPTOSPIROSIS

DIAGNOSIS OF LEPTOSPIROSIS AND THE TYPING OF ISOLATES

GAPS IN KNOWLEDGE AND ANTICIPATED DEVELOPMENTS

ACKNOWLEDGMENTS

REFERENCES

29 Mycoplasma

INTRODUCTION

CHARACTERISTICS OF THE ORGANISM

SOURCES OF THE BACTERIUM

BACTERIAL VIRULENCE FACTORS

PATHOGENESIS

INTERACTIONS

PROTECTIVE IMMUNITY

CONCLUSIONS

REFERENCES

30 Chlamydia

INTRODUCTION

CLASSIFICATION

HOST–PARASITE RELATIONSHIP: CLINICAL DISEASE AND PATHOGENESIS

LIFE CYCLE

ABERRANT DEVELOPMENT CYCLE

HOST RESPONSE

PREVENTION AND CONTROL

FUTURE DIRECTIONS

REFERENCES

31 Rickettsiales

INTRODUCTION

FAMILY ANAPLASMATACEAE

FAMILY RICKETTSIACEAE

REFERENCES

Index

Figures

Edition first published 2010

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Library of Congress Cataloging-in-Publication Data

Pathogenesis of bacterial infections in animals/edited by Carlton L. Gyles... [et al.]. – 4th ed.

p.; cm.

Includes bibliographical references and index.

ISBN 978-0-8138-1237-3 (hardback: alk. paper)

1. Bacterial diseases in animals. I. Gyles, C. L. (Carlton L.), 1940-

[DNLM: 1. Bacterial Infections-veterinary.

2. Bacteria-pathogenicity. SF 780.3 P297 2010] SF780.3.P37 2010

636.089'692-dc22

2009050998

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Preface

The fourth edition of Pathogenesis of Bacterial Infections in Animals captures the fascinating and rapid developments in understanding of the mechanisms of virulence of the major bacterial pathogens of animals. The book is the product of the efforts of 74 authors, all experts in the field on which they have written. The authors come from 13 countries: Australia, Brazil, Belgium, Canada, Germany, Ireland, Israel, Mexico, Norway, Switzerland, the United Kingdom, the United States, and the West Indies.

There have been a few changes in the chapters that were present in the third edition. We omitted the chapters on Shigella and Erysipelothrix rhusio-pathiae. We decided against a chapter on Shigella because its primary importance is as a human pathogen and on E. rhusiopathiae because there is a very limited literature on mechanisms of disease by this organism. This is likely because effective vaccination and control of the disease have reduced the opportunities for funded research on pathogenesis. We added a chapter on subversion of the immune response by bacterial pathogens, because this subject is an important and underemphasized aspect of pathogenesis of many bacterial infections and there have been new insights into the mechanisms employed by bacteria to thwart the host immune response. We presented Pasteurella and Mannheimia as separate chapters to reflect important differences in pathogenesis in these two genera.

One of the challenges in preparing the book was the question of adequate attribution of research findings. Given the volume of literature on each pathogen, there was a danger that too much of the book would be a listing of references. However, the ready availability of excellent modern bibliographic search systems means that the book does not have to serve as the only source of references on pathogenesis of bacterial infections in animals. We therefore made the decision to curtail the number of references, recognizing with regret that not all researchers who made contributions to the literature will be recognized.

This book is possible because a vast number of people believe in sharing their knowledge and perspective with the rest of the bacterial pathogenesis community. It is based on the work of hundreds of researchers, whose ideas, innovation, and research skills have produced the body of knowledge on which we draw. The authors of the chapters in this book have presented captivating stories of bacterial pathogenesis based on their work and that of their colleagues. Several authors created illustrations that are valuable adjuncts to description of pathogenesis. In many cases, publishers and colleagues kindly gave permission for the use of illustrations in the book.

Although molecular pathogenesis is a major aspect in almost every chapter, authors have been careful to place pathogenesis in its broader context. The extent of this context varies from one pathogen to another, partly because bacterial diseases develop under widely varying circumstances and partly because the extent of knowledge of the circumstances varies considerably. As in the previous editions, we have presented both the overview of pathogenesis, including relevant events that occur in editor; Nancy Simmerman, editorial assistant; and the herd or flock and its environment, and activities Justin Jeffryes, commissioning editor. that take place at the cellular and molecular levels.

Finally, we wish to thank our publishers who have been extremely helpful in transforming the writings of 64 individuals into a beautiful book. Special thanks go to Erin Magnani, the production editor; Nancy Simmerman, editorial assistant; and Justin Jeffryes, commissioning editor.

Carlton L. Gyles

John F. Prescott

J. Glenn Songer

Charles O. Thoen

Contributors

Ben Adler Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University VIC 3800, Australia

Art A. Andersen National Animal Disease Center, Agriculturla Research Service, Ames IA50010, USA

John A. Angelos Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616

Vasco Azevedo Departmento de Biologia Geral, ICB/UFMG, Pampulha, Belo Horizonte, Minas Gerais, Brazil, CP 486 CEP 31270-901

Raul G.Barletta Department of Veterinary and Biomedical Sciences University of Nebraska, Lincoln, NE, USA

Paul Barrow School of Veterinary Medicine and Science, University of Nottingham. Loughborough, Sutton Bonington, LE12 5RD, UK

Bryan Belaire Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa 50011, USA

Molly A. Bergman Dept of Microbiology, Tufts University, 136 Harrison Ave, Boston MA 02111

Patrick Boerlin Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada

Helge Bohnel Institute of Tropical Animal Health, Georg-August-University Kellnerweg 6, 37077 Gottingen, Germany

Nicole Borel Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

J. D. Boyce Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University VIC 3800, Australia

Glenn F. Browning Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia

Rebecca Chafel Brandeis University, 415 South Street, Waltham, MA 02454, USA

Lynette Corbeil Department of Pathology, School of Medicine, University of California, San Diego, 200 West Arbor Drive, San Diego, CA 92103–8416, USA.

Charles Czuprynski Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA

AlejandroDe la Peña-Moctezuma Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Coyoacán 04510, Mexico

Luc A. Devriese Faculty of Veterinary Medicine, Ghent University, Salisburylann 133, B9820 Merelbeke, Belgium

John M.Fairbrother GREMIP, Faculté de médecine vétérinaire, Université de Montréal, 3200 Sicotte, C.P. 5000, Saint-Hyacinthe, Quebec, Canada J2S 7C6

Connie J. Gebhart Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA.

Frank Gessler Institute of Tropical Animal Health, Georg-August-University, Kellnerweg 6, 37077 Gottingen, Germany

Roberto M. C. Guedes Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA.

Carlton L. Gyles Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada

Freddy Haesebrouck Faculty of Veterinary Medicine, Ghent University, Salisburylann 133, B9820 Merelbeke, Belgium

David J. Hampson School of Veterinary and Biopmedical Sciences, Murdoch University, Murdoch, Western Australia 6150, Australia

Marina Harper Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University VIC 3800, Australia

Shimon Harrus School of Veterinary Medicine, The Hebrew University of Jerusalem, P. O. Box 12 Rehovot, 76100, Israel

Eric Harvill Department of Veterinary Science, The Pennsylvania State University, 115 Henning Building, University Park, PA 16802

Katleen Hermans Faculty of Veterinary Medicine, Ghent University, Salisburylann 133, B9820 Merelbeke, Belgium

Doug Hodgins Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada

Thomas J. Inzana Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of, Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA

Lynn A. Joens Department of Veterinary Science and Microbiology, University of Arizona, 1117 East Lowell Street, Tucson, AZ 85721, USA.

Michael Jones School of Veterinary Medicine and Science, University of Nottingham. Loughborough, Sutton Bonington, LE12 5RD, UK

Sophia Kathariou Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695–7624, USA.

Ruth M. Kennan Department of Microbiology, Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Victoria 3800, Australia

Patrick Kelly Ross University School of Veterinary Medicine, Basseterre, Saint Kitts, West Indies

Joseph S. Lam Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON, N1G 2W1

Reggie Y. C. Lo Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON, N1G 2W1, Canada

Janet I. MacInnes Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1

Suman Mahan Department of Infectious Diseases and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611–0880, USA.

Marc Marenda Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia

Philip F Markham Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia

Jody M. Matewish Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON, N1G 2W1

Joan Mecsas Department of Microbiology and Molecular Biology, Tufts University, Boston, MA, USA

Wim G. Meijer, School of Biomolecular and Biomedical Science, University College Dublin, Dublin 4, Ireland

Anderson Miyoshi, Institute of Biological Sciences, Federal University of Minas Gerais, Pampulha, Belo Horizonte, Minas Gerais, Brazil, CP 486 CEP 31270–901

Jeremy Mogridge Canada Research Chair in Bacterial Pathogenesis, Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Robert J. Moore CSIRO Livestock Industries, Australian Animal Health Laboratory, Private Bag 24, Geelong, Victoria 3220, Australia

T. G. Nagaraja Department of Diagnostic Medicine/ Pathobiology, Kansas State University, Manhattan, Kansas, USA.

Amir H. Noormohammadi Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia

Ingrid Olsen Department of Animal Health, National Veterinary Institute, Pb 750 Sentrum, 0106 Oslo, Norway

Steven B.Olsen National Animal Disease Center, USDA, ARS, Ames, IA 50010, USA

Luis G. C.Pacheco Institute of Biological Sciences, Federal University of Minas Gerais, Pampulha,Belo Horizonte, Minas Gerais, Brazil, CP 486 CEP 31270–901

Frank Pasmans Laboratory of Veterinary Bacteriology and Mycology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B9820 Merelbeke, Belgium

Andi Pospischil Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland

Keith Poulsen Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI 53706, USA

John F. Prescott Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada

Karen Register B-13, Respiratory Diseases of Livestock Research, UnitUSDA/ARS/National Animal Disease Center, 2300 Dayton Dr., Ames, IA 50010

Julian I. Rood Department of Microbiology, Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Victoria 3800, Australia

R. Martin Roop II Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834

Indra Sandal Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, United States

Nubia Seyffert Institute of Biological Sciences, Federal University of Minas Gerais, Pampulha, Belo Horizonte, Minas Gerais, Brazil, CP 486 CEP 31270–901

Sean V. Shadomy Bacterial Zoonoses Branch, Centers for Disease Control and Prevention, 1600 Clifton Road Mailstop C09, Atlanta, GA 30333

Patricia Shewen Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada

J. Glenn Songer Department of Veterinary Science and Microbiology, The University of Arizona, Tucson, AZ 85721, USA

Charles O. Thoen Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA

Nicholas R. Thomson Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

John F. Timoney Department of Veterinary Medicine, 108 Maxwell H. Gluck Equine Research Institute, University of Kentucky, Lexington, KY 40546–0099, USA

Peter C. Turnbull Arjemptur Technology Ltd., c/o 86 St Mark's Avenue, Salisbury SP1 3DW, UK.

J. A. Vasquez-Boland Division of Microbial Pathogenesis, Centre for Infectious Diseases, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom

Trevor Waner Israel Institute for Biological Research, PO Box 19, Ness Ziona, 74100 Israel

Erin L. Westman Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, Guelph, ON, N1G 2W1

Kevin G. Whithear Department of Veterinary Science, The University of Melbourne, Victoria 3010, Australia

Ian W. Wilkie Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University VIC 3800, Australia

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 host–pathogen 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 non-fimbrial 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 adhesion molecule internalin A (InlA) promotes uptake of the bacterium into intestinal epithelial cells by binding to Ecadherin. 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.

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