Preface xv

List of Contributors xvii

About the Companion Website xxv

1 Themes in Bacterial Pathogenesis 1
John F. Prescott

Introduction 1

The Basic Elements of Bacterial Pathogenesis 1

Concepts of Bacterial Virulence are Being Refined 5

Host-Pathogen Communications are Critical 9

Pathogenesis in the Post-Genomic Era 11

Gaps in Knowledge and Anticipated Directions 13

References 13

2 Evolution of Bacterial Pathogens 15
Patrick Boerlin

What are Pathogens and How Do They Emerge? 15

Bacterial Fitness and Virulence 17

Sources of Genetic Diversity, Population Structure, and Genome Plasticity 18

Pathogenicity Islands 20

Bacteriophages and Their Role in Pathogen Evolution and Virulence 22

Examples of Virulence Evolution 23

Gaps in Knowledge and Anticipated Directions 27

References 28

3 Understanding Pathogenesis Through Pathogenomics and Bioinformatics 32
Gregorio Iraola and John D. Boyce

Introduction 32

How Mutations Generate Bacterial Diversity 34

Genome Sequencing Technologies 36

Genome Assembly 38

Gene Prediction and Annotation 39

Defining Prokaryotic Species from Genomes 41

The Pangenome Concept, Reconstruction, and Comparative Analyses 41

Phylogenomics and Genome-Wide Association Studies 42

Functional Genomics for Understanding Host-Pathogen Interactions 44

Reverse Vaccinology 48

Gaps in Knowledge and Anticipated Directions 51

References 52

4 Experimental Approaches to Understanding Pathogenesis 57
Francesca L. Short and Janet I. MacInnes

Introduction 57

Testing Koch's Postulates 57

Virulence Factors and Main Steps in Pathogenesis 58

Molecular Koch's Postulates 60

Refining Animal Usage 60

Experimental Approaches for Virulence Factor Discovery and Validation 62

Approaches for Virulence Factor Discovery 63

Gene Disruption Approaches for Virulence Factor Discovery 71

Bringing It All Together: Validation and Further Characterization of Virulence Factors 73

Two Stories of Virulence Factor Discovery and Characterization: Pasteurella multocida Capsule, and Mycoplasma bovis Adhesins 74

Gaps in Knowledge and Anticipated Directions 75

References 76

5 Subversion of the Immune Response by Bacterial Pathogens 79
Douglas C. Hodgins, Raveendra R. Kulkarni, and Patricia E. Shewen

Introduction 79

Subversion of Innate Responses 80

Subversion of Adaptive Immunity 85

Manipulation of Cell Fate 88

Non-Coding RNA and Host-Pathogen Interactions 91

Epigenetic and Genetic Modulation 92

Gaps in Knowledge and Anticipated Directions 94

References 94

6 Chinks in the Armor 99
Allison C. Leonard, Celine Stoica, and Georgina Cox

Introduction 99

Virulence Factors: Pathogenesis-Based Targets to Combat Bacterial Pathogens 99

Targeting Bacterial Host Cell Adhesion and Biofilm Formation 100

Quorum Sensing Inhibition 104

Interfering with Two-Component Regulatory Systems 105

Inhibiting Bacterial Motility 106

Toxin Neutralization 107

Inhibitors of Bacterial Secretion Systems 107

Targeting Nutrient Acquisition: Starving the Pathogen 110

Antivirulence Phage Therapy 111

Bacterial Drug Efflux Pumps as Pathogenesis-Based Antibacterial Targets 112

Gaps in Knowledge and Anticipated Directions 112

References 113

7 Escherichia coli 117
John M. Fairbrother and Carlton L. Gyles

Introduction 117

Pathotypes of E. coli and Associated Disease and Pathological Changes in Animals 119

Virulence Factors of Pathogenic E. coli 126

Pathogenesis of Enterotoxigenic E. coli 141

Pathogenesis of Enteropathogenic E. coli Disease 144

Pathogenesis of Shiga Toxin-Producing E. coli Disease 146

Pathogenesis of Extraintestinal Pathogenic E. coli Infections 149

Gaps in Knowledge and Anticipated Directions 156

References 157

8 Salmonella 162
Paul A. Barrow, Michael A. Jones, Kate C. Mellor, and Nick R. Thomson

Introduction 162

Characteristics of the Organism 162

Types of Disease and Pathologic Changes 167

Salmonella Infections in Different Major Farmed Animal Species 169

Virulence Factors 174

Pathogenesis 179

Immunity to Infection and its Manipulation by Salmonella 186

Antimicrobial Resistance 190

Gaps in Knowledge and Anticipated Directions 191

References 192

9 Yersinia 200
Anne-Sophie Le Guern and Javier Pizarro-Cerdá

Introduction 200

Characteristics of the Organism 200

Pathogenic Species 200

Taxonomy 201

Major Virulence Factors of the Highly Pathogenic Yersinia 203

Yersinia pestis 205

Yersinia pseudotuberculosis and Yersinia enterocolitica 209

Yersinia ruckeri 213

Yersinia entomophaga 213

Control of Yersinia Infections 214

Gaps in Knowledge and Anticipated Directions 214

References 215

10 Pasteurella 221
Marina Harper, Thomas R. Smallman, and John D. Boyce

Introduction 221

Characteristics of the Organism 221

Source of Infection: Ecology, Evolution, and Epidemiology 223

Types of Disease and Pathologic Changes 223

Virulence Factors and Pathogenomics 225

Regulation of Virulence 233

Pathogenesis 235

Immunity 236

Control 238

Gaps in Knowledge and Anticipated Directions 239

References 239

11 Mannheimia and Bibersteinia 244
Jeff L. Caswell and Charles J. Czuprynski

Introduction 244

Characteristics of the Organism 244

Pathogenic Species 245

Source of Infection: Ecology, Evolution, and Epidemiology 245

Types of Disease and Pathologic Changes 247

Virulence Factors and Pathogenomics 249

Regulation of Virulence 250

Pathogenesis 251

Immunity 254

Control 254

Gaps in Knowledge and Anticipated Directions 255

References 256

12 Actinobacillus 262
Janine T. Bossé, Adina R. Bujold, and Lu Li

Introduction 262

Actinobacillus pleuropneumoniae 262

Actinobacillus lignieresii 277

Actinobacillus equuli 278

Actinobacillus suis 279

Gaps in Knowledge and Future Directions 281

References 283

13 Other Pasteurellaceae: Avibacterium, Bibersteinia, Gallibacterium, Glaesserella, and Histophilus 290
Anders M. Bojesen, Virginia Aragon, and Pat J. Blackall

Introduction 290

Avibacterium 290

Bibersteinia 292

Gallibacterium 295

Glaesserella parasuis 301

Histophilus 309

References 311

14 Pseudomonas 318
Erin L. Westman, Véronique L. Taylor, and Joseph S. Lam

Introduction 318

Characteristics of the Organism 318

Pathogenic Species 319

Sources of Infection: Ecology, Evolution, and Epidemiology 320

Types of Disease and Pathologic Changes 320

Virulence Factors and Pathogenomics 321

Pathogenesis 328

Immunity 330

Control, Prevention, and Treatment 331

Gaps in Knowledge and Anticipated Directions 335

References 337

15 Moraxella 344
John A. Angelos

Introduction 344

Infectious Bovine Keratoconjunctivitis 344

Pathogenesis of Moraxella bovis Infection 346

Immunity 352

Control 354

Gaps in Knowledge and Future Directions 354

References 355

16 Brucella 361
Clayton C. Caswell, Angela Arenas-Gamboa, and Jeff T. Foster

Introduction 361

Characteristics of the Organism 361

Pathogenic Species 362

Source of Infection: Ecology, Evolution, and Epidemiology 362

Types of Disease and Pathologic Changes 363

Virulence Factors 366

Regulation of Virulence 368

Pathogenomics 369

Pathogenesis 370

Immunity 370

Control 371

Gaps in Knowledge and Anticipated Directions 371

References 372

17 Bordetella 376
Colleen J. Sedney, Tracy L. Nicholson, and Eric T. Harvill

Introduction 376

Characteristics of the Organisms 376

Pathogenic Species 377

Source of Infection: Ecology and Epidemiology 379

Types of Disease and Pathologic Changes 380

Virulence Factors 380

Regulation of Virulence 385

Pathogenesis 385

Immunity 385

Control 387

Gaps in Knowledge and Anticipated Directions 389

References 389

18 Campylobacter 393
Zuowei Wu, Orhan Sahin, and Qijing Zhang

Introduction 393

Diseases, Etiology, and Ecology 394

Clinical Observations and Pathologic Changes 397

Pathogenesis and Virulence Factors 398

Pathogenomics and Evolution 402

Immunity 405

Control 406

Gaps in Knowledge and Future Directions 407

References 408

19 Helicobacter 413
Chloë De Witte, Helena Berlamont, and Freddy Haesebrouck

Introduction 413

Gastric Helicobacters 413

Enterohepatic Helicobacters 425

Gaps in Knowledge and Future Directions 426

References 427

20 Chlamydia and Coxiella 433
Martina Jelocnik, Wilhelmina M. Huston, and Hayley J. Newton

Introduction 433

Chlamydiae 433

Characteristics of the Organism 433

Source of Infection: Ecology, Evolution and Epidemiology 436

Types of Disease and Pathologic Changes 436

Pathogenesis 442

Immunity and Control 442

Gaps in Knowledge and Anticipated Directions 443

Coxiella burnetii 443

Characteristics of the Organism 444

Source of Infection: Ecology, Evolution and Epidemiology 445

Types of Disease and Pathologic Changes 445

Virulence Factors and Pathogenomics 447

Immunity and Control 448

Gaps in Knowledge and Anticipated Directions 449

References 449

21 Rickettsiales 456
Jere W. McBride, Roman R. Ganta, and David H. Walker

Introduction 456

Family Anaplasmataceae 457

Anaplasma Species 457

Ehrlichia Species 463

Neorickettsia Species 474

Family Rickettsiaceae 476

Rickettsia Species 476

References 480

22 Lawsonia intracellularis 486
Roberto M. C. Guedes, Fabio A. Vannucci, and Connie J. Gebhart

Introduction 486

Characteristics of the Organism 486

Sources of Infection: Ecology and Epidemiology 489

Types of Disease and Pathologic Changes 490

Virulence Factors and Pathogenomics 491

Pathogenesis 492

Immunity 496

Control 497

Gaps in Knowledge and Anticipated Directions 497

References 498

23 Leptospira 502
Cyrille Goarant, Ben Adler, and Alejandro de la Peña Moctezuma

Introduction 502

Characteristics of the Organism 502

Leptospira Species 505

Source of Infection: Ecology, Evolution, and Epidemiology 505

Clinical Presentation and Signs 511

Virulence Factors and Pathogenomics 511

Regulation of Virulence 514

Pathogenesis 514

Immunity 516

Control 518

Gaps in Knowledge and Anticipated Directions 518

References 519

24 Brachyspira 528
Joseph E. Rubin and Judith Rohde

Introduction 528

Characteristics of the Organism 528

Pathogenic Species and Disease Associations 529

Source of Infection: Ecology, Evolution, and Epidemiology 530

Virulence Factors and Pathogenomics 531

Pathogenesis 531

Immunity 537

Control 538

Gaps in Knowledge and Anticipated Directions 538

References 539

25 Staphylococcus 543
Amy C. Pickering, Andreas F. Haag, José R. Penades, and J. Ross Fitzgerald

Introduction 543

Characteristics of the Organism 543

Pathogenic Species 544

Staphylococcus aureus Infections in Cattle 546

Staphylococcus aureus Infections in Poultry 551

Staphylococcus aureus Infections in Rabbits 553

Staphylococcus hyicus Infections in Pigs 554

Staphylococcus pseudintermedius Infections in Dogs 556

Gaps in Knowledge and Future Directions 559

References 560

26 Streptococcus 565
John F. Timoney

Introduction 565

Characteristics of the Organism 565

Pathogenic Species 565

Streptococcus agalactiae 567

Streptococcus dysgalactiae 569

Streptococcus uberis 570

Streptococcus equi 571

Streptococcus zooepidemicus 577

Streptococcus canis 579

Streptococcus suis 580

Gaps in Knowledge and Anticipated Directions 583

References 583

27 Bacillus anthracis 588
Joachim Frey

Introduction 588

Characteristics of the Organism: Taxonomy and Phylogeny 588

Source and Spread of the Infection: Ecology, Evolution, and Epidemiology 591

Types of Disease and Pathologic Changes 592

Virulence Factors and Pathogenomics 594

Regulation of Virulence 595

Pathogenesis 596

Immunity and Vaccines 598

Control and Prevention of Anthrax 598

Gaps in Knowledge and Anticipated Directions 600

References 601

28 Enteric Clostridia 607
Evelien Dierick, Evy Goossens, John F. Prescott, Richard Ducatelle, and Filip Van Immerseel

Introduction 607

Clostridium perfringens 607

Characteristics of the Organism 607

Pathogenic Types 608

Sources of Infections: Ecology, Evolution and Epidemiology 608

Types of Disease and Pathologic Changes 611

Virulence Factors 616

Regulation of Virulence 622

The Pathogenesis of Clostridium perfringens Enteric Disease 622

Control 625

Gaps in Knowledge and Anticipated Directions 625

Clostridioides difficile 626

Characteristics of the Organism 626

Source of Infection: Ecology, Evolution and Epidemiology 626

Types of Disease and Pathologic Changes 627

Disease 627

Virulence Factors and Pathogenomics 627

Regulation of Virulence 628

Pathogenesis 629

Immunity 630

Control 630

Gaps in Knowledge and Anticipated Directions 630

Other Enteric Clostridia 630

References 631

29 Histotoxic Clostridia 635
Andrew N. Rycroft

Introduction 635

Characteristics of the Organisms 635

Source of Infection and Basic Pathogenesis 636

Pathogenic Species 636

Clostridium septicum (Malignant Edema/Gas Gangrene) 638

Clostridium chauvoei (Blackleg) 639

Paeniclostridium sordellii 640

Clostridium novyi Type B (Black Disease/Bighead) 642

Clostridium haemolyticum 643

Clostridium perfringens 644

Control 645

Gaps in Knowledge and Future Directions 645

References 646

30 Neurotoxic Clostridia 648
Michel R. Popoff

Introduction 648

Characteristic of the Organisms 648

Clostridium botulinum 648

Clostridium tetani 650

Sources of Infection: Ecology and Epidemiology 652

Diseases 656

Botulism 656

Tetanus 657

Virulence Factors 658

Pathogenesis 659

Control 663

References 664

31 Mycoplasmas 667
Pollob K. Shil, Nadeeka K. Wawegama, Glenn F. Browning, Amir H. Noormohammadi, and Marc

S. Marenda

Introduction 667

Characteristics of the Organisms 667

Pathogenic Species 668

Source of Infection: Ecology, Evolution, and Epidemiology 668

Virulence Factors and Pathogenomics 670

Regulation of Virulence 674

Types of Disease and Pathologic Changes 674

Pathogenesis 680

Immunity 688

Control 690

Gaps in Knowledge and Anticipated Directions 690

References 691

32 Corynebacterium, Arcanobacterium, and Trueperella 701
Thiago D. Barral, Ricardo W. Portela, Núbia Seyffert, and Robert J. Moore

Corynebacterium 701

Corynebacterium pseudotuberculosis 701

Bovine Pyelonephritis Caused by Corynebacterium Species 706

Other Animal Pathogenic Corynebacterium Species 706

Arcanobacterium 707

Trueperella 709

Gaps in Knowledge and Future Directions 710

References 710

33 Rhodococcus equi 715
José A. Vázquez-Boland, Macarena G. Sanz, and John F. Prescott

Introduction 715

Characteristics of the Organism 715

Source of Infection and Epidemiology 717

Types of Disease and Pathologic Changes 720

Virulence Factors 721

Evolution of Rhodococcus equi Virulence 723

Pathogenesis 724

Immunity 726

Treatment and Control 728

Gaps in Knowledge and Anticipated Directions 730

References 731

34 Mycobacterium 736
Karren M. Plain, Karen Stevenson, Richard J. Whittington, and Nathalie Winter

Introduction 736

Characteristics of the Organism 736

Sources of Infection 738

Source of Infection: Evolution and Epidemiology 739

Virulence Factors and Pathogenomics 740

Regulation of Virulence 742

Types of Disease 743

Pathogenesis 744

Adaptive Immunity and Mycobacterial Pathogenesis 748

Control 750

Gaps in Knowledge and Anticipated Directions 750

References 752

35 Gram-Negative Anaerobes 757
John F. Prescott

Introduction 757

General Bacterial Pathogenesis Aspects 757

Fusobacterium 759

Bacteroides 763

Prevotella and Porphyromonas 764

Dichelobacter nodosus 765

Treponema 767

Gaps in Knowledge and Anticipated Developments 768

References 768

Index 773