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This highly anticipated update of the acclaimed textbook draws on the latest research to give students the knowledge and tools to explore the mechanisms by which bacterial pathogens cause infections in humans and animals. Written in an approachable and engaging style, the book uses illustrative examples and thought-provoking exercises to inspire students with the potential excitement and fun of scientific discovery.
Completely revised and updated, and for the first time in stunning full-color, Bacterial Pathogenesis: A Molecular Approach, Fourth Edition, builds on the core principles and foundations of its predecessors while expanding into new concepts, key findings, and cutting-edge research, including new developments in the areas of the microbiome and CRISPR as well as the growing challenges of antimicrobial resistance. All-new detailed illustrations help students clearly understand important concepts and mechanisms of the complex interplay between bacterial pathogens and their hosts. Study questions at the end of each chapter challenge students to delve more deeply into the topics covered, and hone their skills in reading, interpreting, and analyzing data, as well as devising their own experiments. A detailed glossary defines and expands on key terms highlighted throughout the book. Written for advanced undergraduate, graduate, and professional students in microbiology, bacteriology, and pathogenesis, this text is a must-have for anyone looking for a greater understanding of virulence mechanisms across the breadth of bacterial pathogens.
Completely revised and updated, and for the first time in stunning full-color, Bacterial Pathogenesis: A Molecular Approach, Fourth Edition, builds on the core principles and foundations of its predecessors while expanding into new concepts, key findings, and cutting-edge research, including new developments in the areas of the microbiome and CRISPR as well as the growing challenges of antimicrobial resistance. All-new detailed illustrations help students clearly understand important concepts and mechanisms of the complex interplay between bacterial pathogens and their hosts. Study questions at the end of each chapter challenge students to delve more deeply into the topics covered, and hone their skills in reading, interpreting, and analyzing data, as well as devising their own experiments. A detailed glossary defines and expands on key terms highlighted throughout the book. Written for advanced undergraduate, graduate, and professional students in microbiology, bacteriology, and pathogenesis, this text is a must-have for anyone looking for a greater understanding of virulence mechanisms across the breadth of bacterial pathogens.
This highly anticipated update of the acclaimed textbook draws on the latest research to give students the knowledge and tools to explore the mechanisms by which bacterial pathogens cause infections in humans and animals. Written in an approachable and engaging style, the book uses illustrative examples and thought-provoking exercises to inspire students with the potential excitement and fun of scientific discovery.
Completely revised and updated, and for the first time in stunning full-color, Bacterial Pathogenesis: A Molecular Approach, Fourth Edition, builds on the core principles and foundations of its predecessors while expanding into new concepts, key findings, and cutting-edge research, including new developments in the areas of the microbiome and CRISPR as well as the growing challenges of antimicrobial resistance. All-new detailed illustrations help students clearly understand important concepts and mechanisms of the complex interplay between bacterial pathogens and their hosts. Study questions at the end of each chapter challenge students to delve more deeply into the topics covered, and hone their skills in reading, interpreting, and analyzing data, as well as devising their own experiments. A detailed glossary defines and expands on key terms highlighted throughout the book. Written for advanced undergraduate, graduate, and professional students in microbiology, bacteriology, and pathogenesis, this text is a must-have for anyone looking for a greater understanding of virulence mechanisms across the breadth of bacterial pathogens.
Completely revised and updated, and for the first time in stunning full-color, Bacterial Pathogenesis: A Molecular Approach, Fourth Edition, builds on the core principles and foundations of its predecessors while expanding into new concepts, key findings, and cutting-edge research, including new developments in the areas of the microbiome and CRISPR as well as the growing challenges of antimicrobial resistance. All-new detailed illustrations help students clearly understand important concepts and mechanisms of the complex interplay between bacterial pathogens and their hosts. Study questions at the end of each chapter challenge students to delve more deeply into the topics covered, and hone their skills in reading, interpreting, and analyzing data, as well as devising their own experiments. A detailed glossary defines and expands on key terms highlighted throughout the book. Written for advanced undergraduate, graduate, and professional students in microbiology, bacteriology, and pathogenesis, this text is a must-have for anyone looking for a greater understanding of virulence mechanisms across the breadth of bacterial pathogens.
Über den Autor
Brenda A. Wilson, Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana-Champaign, Illinois.
Malcolm E. Winkler, Department of Biology, Indiana University, Bloomington, Indiana.
Brian T. Ho, Institute of Structural and Molecular Biology, University College London and Birkbeck, University of London, London, United Kingdom.
Inhaltsverzeichnis
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 . . . 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
Chapter 10 Identification of Virulence Factors: Molecular Approaches for Host Factors 226
Comparative Approaches to Identify Host Factors Required for Infection 227
Transgenic Animal Models 228
In vivo Imaging of Animals during Infection 231
Systems Genetics: Comparative Genomics of the Host Response 231
Screening Approaches to Identify Host Factors Required for Infection 235
Genome-Wide Screening 235
Host Response Profiling to Identify Host Factors Required for Infection 240
Transcriptomics 240
Proteomics 243
Metabolomics 246
The Promise and the Caution 247
Selected Readings 248
Questions 249
Solving Problems in Bacterial Pathogenesis 249
Chapter 11 Bacterial Strategies for Colonization and Survival in the Host 254
What Does Not Kill You Makes You Stronger--Or, a Better Pathogen 255
Preinfection 258
Survival in the External Environment 258
Biofilms 258
Motility and Chemotaxis 260
Colonization of Host Surfaces 263
Penetrating Intact Skin 263
Penetrating the Mucin Layer 263
Evading the Host's Innate Immunity 264
Nutrient and Iron Acquisition Mechanisms 265
Adherence 268
Evading the Host Immune Response 275
Avoiding Complement and Phagocytosis 277
Invasion and Uptake by Host Cells 280
Surviving...
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 . . . 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
Chapter 10 Identification of Virulence Factors: Molecular Approaches for Host Factors 226
Comparative Approaches to Identify Host Factors Required for Infection 227
Transgenic Animal Models 228
In vivo Imaging of Animals during Infection 231
Systems Genetics: Comparative Genomics of the Host Response 231
Screening Approaches to Identify Host Factors Required for Infection 235
Genome-Wide Screening 235
Host Response Profiling to Identify Host Factors Required for Infection 240
Transcriptomics 240
Proteomics 243
Metabolomics 246
The Promise and the Caution 247
Selected Readings 248
Questions 249
Solving Problems in Bacterial Pathogenesis 249
Chapter 11 Bacterial Strategies for Colonization and Survival in the Host 254
What Does Not Kill You Makes You Stronger--Or, a Better Pathogen 255
Preinfection 258
Survival in the External Environment 258
Biofilms 258
Motility and Chemotaxis 260
Colonization of Host Surfaces 263
Penetrating Intact Skin 263
Penetrating the Mucin Layer 263
Evading the Host's Innate Immunity 264
Nutrient and Iron Acquisition Mechanisms 265
Adherence 268
Evading the Host Immune Response 275
Avoiding Complement and Phagocytosis 277
Invasion and Uptake by Host Cells 280
Surviving...
Details
| Erscheinungsjahr: | 2019 |
|---|---|
| Fachbereich: | Pharmazie |
| Genre: | Medizin |
| Rubrik: | Wissenschaften |
| Medium: | Taschenbuch |
| Seiten: | 660 |
| Inhalt: | 660 S. |
| ISBN-13: | 9781555819408 |
| ISBN-10: | 1555819400 |
| Sprache: | Englisch |
| Einband: | Kartoniert / Broschiert |
| Autor: |
Wilson, Brenda A.
Ho, Brian T. Winkler, Malcolm |
| Hersteller: | American Society for Microbiology |
| Maße: | 279 x 215 x 35 mm |
| Von/Mit: | Brenda A. Wilson (u. a.) |
| Erscheinungsdatum: | 01.07.2019 |
| Gewicht: | 1,944 kg |
Über den Autor
Brenda A. Wilson, Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana-Champaign, Illinois.
Malcolm E. Winkler, Department of Biology, Indiana University, Bloomington, Indiana.
Brian T. Ho, Institute of Structural and Molecular Biology, University College London and Birkbeck, University of London, London, United Kingdom.
Inhaltsverzeichnis
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 . . . 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
Chapter 10 Identification of Virulence Factors: Molecular Approaches for Host Factors 226
Comparative Approaches to Identify Host Factors Required for Infection 227
Transgenic Animal Models 228
In vivo Imaging of Animals during Infection 231
Systems Genetics: Comparative Genomics of the Host Response 231
Screening Approaches to Identify Host Factors Required for Infection 235
Genome-Wide Screening 235
Host Response Profiling to Identify Host Factors Required for Infection 240
Transcriptomics 240
Proteomics 243
Metabolomics 246
The Promise and the Caution 247
Selected Readings 248
Questions 249
Solving Problems in Bacterial Pathogenesis 249
Chapter 11 Bacterial Strategies for Colonization and Survival in the Host 254
What Does Not Kill You Makes You Stronger--Or, a Better Pathogen 255
Preinfection 258
Survival in the External Environment 258
Biofilms 258
Motility and Chemotaxis 260
Colonization of Host Surfaces 263
Penetrating Intact Skin 263
Penetrating the Mucin Layer 263
Evading the Host's Innate Immunity 264
Nutrient and Iron Acquisition Mechanisms 265
Adherence 268
Evading the Host Immune Response 275
Avoiding Complement and Phagocytosis 277
Invasion and Uptake by Host Cells 280
Surviving...
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 . . . 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
Chapter 10 Identification of Virulence Factors: Molecular Approaches for Host Factors 226
Comparative Approaches to Identify Host Factors Required for Infection 227
Transgenic Animal Models 228
In vivo Imaging of Animals during Infection 231
Systems Genetics: Comparative Genomics of the Host Response 231
Screening Approaches to Identify Host Factors Required for Infection 235
Genome-Wide Screening 235
Host Response Profiling to Identify Host Factors Required for Infection 240
Transcriptomics 240
Proteomics 243
Metabolomics 246
The Promise and the Caution 247
Selected Readings 248
Questions 249
Solving Problems in Bacterial Pathogenesis 249
Chapter 11 Bacterial Strategies for Colonization and Survival in the Host 254
What Does Not Kill You Makes You Stronger--Or, a Better Pathogen 255
Preinfection 258
Survival in the External Environment 258
Biofilms 258
Motility and Chemotaxis 260
Colonization of Host Surfaces 263
Penetrating Intact Skin 263
Penetrating the Mucin Layer 263
Evading the Host's Innate Immunity 264
Nutrient and Iron Acquisition Mechanisms 265
Adherence 268
Evading the Host Immune Response 275
Avoiding Complement and Phagocytosis 277
Invasion and Uptake by Host Cells 280
Surviving...
Details
| Erscheinungsjahr: | 2019 |
|---|---|
| Fachbereich: | Pharmazie |
| Genre: | Medizin |
| Rubrik: | Wissenschaften |
| Medium: | Taschenbuch |
| Seiten: | 660 |
| Inhalt: | 660 S. |
| ISBN-13: | 9781555819408 |
| ISBN-10: | 1555819400 |
| Sprache: | Englisch |
| Einband: | Kartoniert / Broschiert |
| Autor: |
Wilson, Brenda A.
Ho, Brian T. Winkler, Malcolm |
| Hersteller: | American Society for Microbiology |
| Maße: | 279 x 215 x 35 mm |
| Von/Mit: | Brenda A. Wilson (u. a.) |
| Erscheinungsdatum: | 01.07.2019 |
| Gewicht: | 1,944 kg |
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