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Preface xvii In Memoriam xix About the Authors xxi
Chapter 1 The Power of Bacteria 2 Why Are Bacteria So Much in the Public Health Spotlight Nowadays? 3 Bacteria, a Formidable Ancient Life Form 4 Pressing Current Infectious Disease Issues 6 Emerging and Reemerging Infectious Diseases 6 Foodborne and Waterborne Infections 7 Modern Medicine as a Source of New Diseases 8 Postsurgical and Other Wound Infections 9 Bioterrorism 10 A New Respect for Prevention 10 Surveillance: An Early Warning System 11 Making Hospitals Safe for Patients 12 And Now for Some Good News: You''ve Got a Bacterial Infection! 12 The Helicobacter pylori Revolution 12 The Aftermath 13 Microbiota Shift Diseases 13 A Brave New World of Pathogenesis Research 14 The New Age of Genomics 16 Insights into Pathogen Evolution 17 Modeling the Host-Pathogen Interaction in Experimental Animals 17 Correlation Studies 18 Selected Readings 18 Questions 20
Chapter 2 Skin and Mucosa: The First Lines of Defense against Bacterial Infections 22 The Best Defense: Avoid, Reduce, and Prevent Exposure! 23 Barriers: Skin and Mucosal Membranes 24 The Layers of Cells That Protect the Body 24 Normal Microbiota of the Skin and Mucosa 27 Defenses of the Skin 31 Defenses of Mucosal Surfaces 32 Special Defenses of the Gastrointestinal Tract 34 Special Defenses of the Urogenital Tract 36 Special Defenses of the Respiratory Tract 36 Immune Defenses of the Skin and Mucosa 37 Models for Studying Breaches of Barrier Defenses 38 Selected Readings 39 Questions 39
Chapter 3 The Innate Immune System: Always on Guard 40 Triggering Innate Immune Defenses 41 Innate Immune Cells That Defend Blood and Tissue 42 Neutrophils (PMNs) 42 Monocytes, Macrophages, and Dendritic Cells (DCs) 42 Granulocytes: Basophils, Mast Cells, and Eosinophils 47 Transmigration--How Do Phagocytes Know When and Where to Go? 47 Natural Killer (NK) Cells 48 The Lymphatic System 50 How Phagocytes Recognize and Respond to Bacteria 50 How Phagocytes Kill Bacteria 54 Oxidative Burst in Phagolysosomes 54 Autophagy--Another Pathway for the Killing of Intracellular Pathogens 56 The Complement Cascade 57 Complement Proteins 57 Overview of Complement Pathways and Their Function 58 Steps in Complement Activation 60 Controlling Complement Activation 62 Cytokines and Chemokines--Mediators of Immune Responses 63 Roles of Cytokines and Chemokines in Directing Innate Immune Responses 63 Inflammation and Collateral Damage 65 Septic Shock: The Dark Side of the Innate Defenses 66 Other Innate Defenses of the Body--Nutritional Immunity 69 Selected Readings 70 Questions 70
Chapter 4 The Adaptive Defenses: Antibodies and Cytotoxic T Cells 72 The Specialists: Adapting to a Particular Pathogen Challenge 73 B Cells: Producers of Antibodies 74 The Humoral (Antibody) Immune Response 74 Characteristics of Antibodies and Their Diverse Roles in Preventing Infection 74 Serum Antibodies 76 Secretory Antibodies: Antibodies That Protect Mucosal Surfaces 78 Pathogen and Toxin Neutralization by Antibodies 79 Affinity and Avidity 80 Cytotoxic T Cells, Also Known as Cytotoxic T Lymphocytes (CTLs) 81 Cytotoxic T Lymphocytes: Critical Defense against Intracellular Pathogens 81 Antigen Presentation to the Immune System 82 Processing of Protein Antigens by Dendritic Cells 82 Interaction between APCs and T Cells: The T-Cell-Dependent Response 84 Th-(Th1/Th2/Th17)-Cell-Mediated Immunity 86 Production of Antibodies by B Cells 87 Links between the Innate and Adaptive Defense Systems 88 T-Cell-Independent Antibody Responses 89 Mucosal Immunity: IgA/sIgA Antibodies 89 Development of the Adaptive Immune System from Infancy to Adulthood 92 Adaptive Defense Systems in Nonmammals 93 The Dark Side of the Adaptive Defenses: Autoimmune Disease 93 Selected Readings 94 Questions 94 Solving Problems in Bacterial Pathogenesis 95
Chapter 5 The Microbiota of the Human Body: Microbiomes and Beyond 98 Importance of the Normal Resident Microbial Populations (Microbiota) of the Human Body 99 Characterization of the Body''s Microbiota 100 Taking a Microbial Census by Using Microbial rRNA Gene Sequence Analysis 101 Characterizing Microbiomes by Using Metagenomic Analysis 115 Beyond the Metagenome 117 Overview of the Human Microbiota 123 Skin Microbiota 124 Oropharyngeal Microbiota 125 Microbiota of the Small Intestine and Colon 125 Microbiota of the Vaginal Tract 128 The Other Microbiota: The Forgotten Eukaryotes 130 Selected Readings 130 Questions 131 Solving Problems in Bacterial Pathogenesis 133
Chapter 6 Microbes and Disease: Establishing a Connection 134 History and Relevance of Koch''s Postulates 136 Early Germ Theory 136 Koch''s Postulates: A Set of Criteria Used to Establish a Microbe-Disease Connection 137 Challenges to Satisfying Koch''s Postulates 138 Easier Said than Done
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. 138 The First Postulate: Association of the Microbe with Lesions of the Disease 139 The Second Postulate: Isolating the Bacterium in Pure Culture 140 The Third Postulate: Showing that the Isolated Bacterium Causes Disease Experimentally in Humans or Animals 141 The Fourth Postulate: Reisolating the Bacterium from the Intentionally Infected Animal 143 Modern Alternatives to Satisfy Koch''s Postulates 143 Detecting the Presence of the Pathogen Only in Diseased Tissues 143 Eliminate the Pathogen and Prevent or Cure the Disease 144 Comparative Infectious Disease Causation 147 The Microbiota Shift Disease Problem 147 Koch''s Postulates and Pathogenic Microbial Communities 147 Keystone Pathogens and Microbial Shift Diseases 147 Molecular Koch''s Postulates 149 Concepts of Disease 150 Varieties of Human-Microbe Interactions 150 Views of the Human-Microbe Interaction 150 Virulence as a Complex Phenomenon 152 Selected Readings 152 Questions 153 Solving Problems in Bacterial Pathogenesis 153
Chapter 7 Mechanisms of Genetic Modification and Exchange: Role in Pathogen Evolution 156 Adapt or Perish 158 Acquiring New Virulence Traits by Horizontal Gene Transfer 158 Mechanisms of Genetic Change and Diversification 158 Spontaneous Mutation 158 Phase Variation 159 Antigenic Variation 161 Horizontal Gene Transfer: Mobile Genetic Elements 162 Natural Transformation 162 Conjugation: Plasmids and Transposons 165 Phage Transduction 171 Control of Horizontal Gene Transfer 171 Toxin-Antitoxin Systems--Retaining the Goods 171 Restriction-Modification Systems--Bacterial Innate Immunity from Foreign DNA 173 CRISPR-Cas Systems--Bacterial Adaptive Immunity from Foreign DNA 173 Type 6 Secretion Systems--Bacterial Defense Against Conjugation 174 Pathogenicity Islands and Pathogen Evolution 174 Properties of Pathogenicity Islands 174 Pathogen Evolution in Quantum Leaps 177 Selected Readings 178 Questions 179 Solving Problems in Bacterial Pathogenesis 179
Chapter 8 Identification of Virulence Factors: Measuring Infectivity and Virulence 182 How Does One Experimentally Measure Virulence and Satisfy Koch''s Postulates? 183 Animal Models of Infection 184 Human Volunteers 184 Nonhuman Animal Models 186 Measuring Bacterial Infection in Animal Models 188 Ethical Considerations 188 Animal Model Basics 188 Survival Curve Analysis and Biophotonic Imaging 189 ID50 and LD50 Values 190 Competition Assays 191 Tissue Culture and Organ Culture Models 192 Tissue Culture Models 192 Gentamicin Protection Assay for Cell Adhesion and Invasion 193 Plaque Assay for Intracellular Survival and Cell-to-Cell Spread 195 Fluorescence Microscopy Techniques for Assessing Effects of Pathogens on Host Cells 196 Organ Culture Models 196 The Continuing Need for Reliable and Plentiful Information about Disease Pathology 197 Selected Readings 198 Questions 199 Solving Problems in Bacterial Pathogenesis 200
Chapter 9 Identification of Virulence Factors: Molecular Approaches for Bacterial Factors 202 Finding a Needle in a Haystack 204 Biochemical Approaches 204 Isolation and Purification of Toxic Factors 204 Molecular Genetic Approaches 208 Screening Using Recombinant Genes 208 Reporter Fusions 208 Mutagenesis Screening 210 Genome-wide Sequencing Approaches for Identifying Virulence Genes 214 Tn-Seq Technology to Identify In Vivo-Expressed Genes 214 RNA-Seq Technology to Identify In Vivo-Expressed Genes 216 Comparative Genomic Sequence Analysis for Identifying Virulence Genes 217 Proteomics Approaches for Identifying Virulence Factors 218 Protein Microarrays (Proteoarrays) 218 In Vivo-Induced Antigen Technology (IVIAT) 218 The Importance of Understanding Bacterial Physiology 219 Selected Readings 222 Questions 223 Solving Problems in Bacterial Pathogenesis 223
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