Bacterial Pathogenesis: A Molecular Approach

ISBN-13: 9781555819408 / Angielski / Miękka / 2019 / 660 str.

Brenda A. Wilson; Brian T. Ho; Malcolm E. Winkler

Spis treści

Preface xviiIn Memoriam xixAbout the Authors xxiChapter 1 The Power of Bacteria 2Why Are Bacteria So Much in the Public Health Spotlight Nowadays? 3Bacteria, a Formidable Ancient Life Form 4Pressing Current Infectious Disease Issues 6Emerging and Reemerging Infectious Diseases 6Foodborne and Waterborne Infections 7Modern Medicine as a Source of New Diseases 8Postsurgical and Other Wound Infections 9Bioterrorism 10A New Respect for Prevention 10Surveillance: An Early Warning System 11Making Hospitals Safe for Patients 12And Now for Some Good News: You've Got a Bacterial Infection! 12The Helicobacter pylori Revolution 12The Aftermath 13Microbiota Shift Diseases 13A Brave New World of Pathogenesis Research 14The New Age of Genomics 16Insights into Pathogen Evolution 17Modeling the Host-Pathogen Interaction in Experimental Animals 17Correlation Studies 18Selected Readings 18Questions 20Chapter 2 Skin and Mucosa: The First Lines of Defense against Bacterial Infections 22The Best Defense: Avoid, Reduce, and Prevent Exposure! 23Barriers: Skin and Mucosal Membranes 24The Layers of Cells That Protect the Body 24Normal Microbiota of the Skin and Mucosa 27Defenses of the Skin 31Defenses of Mucosal Surfaces 32Special Defenses of the Gastrointestinal Tract 34Special Defenses of the Urogenital Tract 36Special Defenses of the Respiratory Tract 36Immune Defenses of the Skin and Mucosa 37Models for Studying Breaches of Barrier Defenses 38Selected Readings 39Questions 39Chapter 3 The Innate Immune System: Always on Guard 40Triggering Innate Immune Defenses 41Innate Immune Cells That Defend Blood and Tissue 42Neutrophils (PMNs) 42Monocytes, Macrophages, and Dendritic Cells (DCs) 42Granulocytes: Basophils, Mast Cells, and Eosinophils 47Transmigration--How Do Phagocytes Know When and Where to Go? 47Natural Killer (NK) Cells 48The Lymphatic System 50How Phagocytes Recognize and Respond to Bacteria 50How Phagocytes Kill Bacteria 54Oxidative Burst in Phagolysosomes 54Autophagy--Another Pathway for the Killing of Intracellular Pathogens 56The Complement Cascade 57Complement Proteins 57Overview of Complement Pathways and Their Function 58Steps in Complement Activation 60Controlling Complement Activation 62Cytokines and Chemokines--Mediators of Immune Responses 63Roles of Cytokines and Chemokines in Directing Innate Immune Responses 63Inflammation and Collateral Damage 65Septic Shock: The Dark Side of the Innate Defenses 66Other Innate Defenses of the Body--Nutritional Immunity 69Selected Readings 70Questions 70Chapter 4 The Adaptive Defenses: Antibodies and Cytotoxic T Cells 72The Specialists: Adapting to a Particular Pathogen Challenge 73B Cells: Producers of Antibodies 74The Humoral (Antibody) Immune Response 74Characteristics of Antibodies and Their Diverse Roles in Preventing Infection 74Serum Antibodies 76Secretory Antibodies: Antibodies That Protect Mucosal Surfaces 78Pathogen and Toxin Neutralization by Antibodies 79Affinity and Avidity 80Cytotoxic T Cells, Also Known as Cytotoxic T Lymphocytes (CTLs) 81Cytotoxic T Lymphocytes: Critical Defense against Intracellular Pathogens 81Antigen Presentation to the Immune System 82Processing of Protein Antigens by Dendritic Cells 82Interaction between APCs and T Cells: The T-Cell-Dependent Response 84Th-(Th1/Th2/Th17)-Cell-Mediated Immunity 86Production of Antibodies by B Cells 87Links between the Innate and Adaptive Defense Systems 88T-Cell-Independent Antibody Responses 89Mucosal Immunity: IgA/sIgA Antibodies 89Development of the Adaptive Immune System from Infancy to Adulthood 92Adaptive Defense Systems in Nonmammals 93The Dark Side of the Adaptive Defenses: Autoimmune Disease 93Selected Readings 94Questions 94Solving Problems in Bacterial Pathogenesis 95Chapter 5 The Microbiota of the Human Body: Microbiomes and Beyond 98Importance of the Normal Resident Microbial Populations (Microbiota) of the Human Body 99Characterization of the Body's Microbiota 100Taking a Microbial Census by Using Microbial rRNA Gene Sequence Analysis 101Characterizing Microbiomes by Using Metagenomic Analysis 115Beyond the Metagenome 117Overview of the Human Microbiota 123Skin Microbiota 124Oropharyngeal Microbiota 125Microbiota of the Small Intestine and Colon 125Microbiota of the Vaginal Tract 128The Other Microbiota: The Forgotten Eukaryotes 130Selected Readings 130Questions 131Solving Problems in Bacterial Pathogenesis 133Chapter 6 Microbes and Disease: Establishing a Connection 134History and Relevance of Koch's Postulates 136Early Germ Theory 136Koch's Postulates: A Set of Criteria Used to Establish a Microbe-Disease Connection 137Challenges to Satisfying Koch's Postulates 138Easier Said than Done . . . 138The First Postulate: Association of the Microbe with Lesions of the Disease 139The Second Postulate: Isolating the Bacterium in Pure Culture 140The Third Postulate: Showing that the Isolated Bacterium Causes Disease Experimentally in Humans or Animals 141The Fourth Postulate: Reisolating the Bacterium from the Intentionally Infected Animal 143Modern Alternatives to Satisfy Koch's Postulates 143Detecting the Presence of the Pathogen Only in Diseased Tissues 143Eliminate the Pathogen and Prevent or Cure the Disease 144Comparative Infectious Disease Causation 147The Microbiota Shift Disease Problem 147Koch's Postulates and Pathogenic Microbial Communities 147Keystone Pathogens and Microbial Shift Diseases 147Molecular Koch's Postulates 149Concepts of Disease 150Varieties of Human-Microbe Interactions 150Views of the Human-Microbe Interaction 150Virulence as a Complex Phenomenon 152Selected Readings 152Questions 153Solving Problems in Bacterial Pathogenesis 153Chapter 7 Mechanisms of Genetic Modification and Exchange: Role in Pathogen Evolution 156Adapt or Perish 158Acquiring New Virulence Traits by Horizontal Gene Transfer 158Mechanisms of Genetic Change and Diversification 158Spontaneous Mutation 158Phase Variation 159Antigenic Variation 161Horizontal Gene Transfer: Mobile Genetic Elements 162Natural Transformation 162Conjugation: Plasmids and Transposons 165Phage Transduction 171Control of Horizontal Gene Transfer 171Toxin-Antitoxin Systems--Retaining the Goods 171Restriction-Modification Systems--Bacterial Innate Immunity from Foreign DNA 173CRISPR-Cas Systems--Bacterial Adaptive Immunity from Foreign DNA 173Type 6 Secretion Systems--Bacterial Defense Against Conjugation 174Pathogenicity Islands and Pathogen Evolution 174Properties of Pathogenicity Islands 174Pathogen Evolution in Quantum Leaps 177Selected Readings 178Questions 179Solving Problems in Bacterial Pathogenesis 179Chapter 8 Identification of Virulence Factors: Measuring Infectivity and Virulence 182How Does One Experimentally Measure Virulence and Satisfy Koch's Postulates? 183Animal Models of Infection 184Human Volunteers 184Nonhuman Animal Models 186Measuring Bacterial Infection in Animal Models 188Ethical Considerations 188Animal Model Basics 188Survival Curve Analysis and Biophotonic Imaging 189ID50 and LD50 Values 190Competition Assays 191Tissue Culture and Organ Culture Models 192Tissue Culture Models 192Gentamicin Protection Assay for Cell Adhesion and Invasion 193Plaque Assay for Intracellular Survival and Cell-to-Cell Spread 195Fluorescence Microscopy Techniques for Assessing Effects of Pathogens on Host Cells 196Organ Culture Models 196The Continuing Need for Reliable and Plentiful Information about Disease Pathology 197Selected Readings 198Questions 199Solving Problems in Bacterial Pathogenesis 200Chapter 9 Identification of Virulence Factors: Molecular Approaches for Bacterial Factors 202Finding a Needle in a Haystack 204Biochemical Approaches 204Isolation and Purification of Toxic Factors 204Molecular Genetic Approaches 208Screening Using Recombinant Genes 208Reporter Fusions 208Mutagenesis Screening 210Genome-wide Sequencing Approaches for Identifying Virulence Genes 214Tn-Seq Technology to Identify In Vivo-Expressed Genes 214RNA-Seq Technology to Identify In Vivo-Expressed Genes 216Comparative Genomic Sequence Analysis for Identifying Virulence Genes 217Proteomics Approaches for Identifying Virulence Factors 218Protein Microarrays (Proteoarrays) 218In Vivo-Induced Antigen Technology (IVIAT) 218The Importance of Understanding Bacterial Physiology 219Selected Readings 222Questions 223Solving Problems in Bacterial Pathogenesis 223Chapter 10 Identification of Virulence Factors: Molecular Approaches for Host Factors 226Comparative Approaches to Identify Host Factors Required for Infection 227Transgenic Animal Models 228In vivo Imaging of Animals during Infection 231Systems Genetics: Comparative Genomics of the Host Response 231Screening Approaches to Identify Host Factors Required for Infection 235Genome-Wide Screening 235Host Response Profiling to Identify Host Factors Required for Infection 240Transcriptomics 240Proteomics 243Metabolomics 246The Promise and the Caution 247Selected Readings 248Questions 249Solving Problems in Bacterial Pathogenesis 249Chapter 11 Bacterial Strategies for Colonization and Survival in the Host 254What Does Not Kill You Makes You Stronger--Or, a Better Pathogen 255Preinfection 258Survival in the External Environment 258Biofilms 258Motility and Chemotaxis 260Colonization of Host Surfaces 263Penetrating Intact Skin 263Penetrating the Mucin Layer 263Evading the Host's Innate Immunity 264Nutrient and Iron Acquisition Mechanisms 265Adherence 268Evading the Host Immune Response 275Avoiding Complement and Phagocytosis 277Invasion and Uptake by Host Cells 280Surviving Phagocytosis 281Cell-to-Cell Spread 286Tissue Penetration and Dissemination 288Beyond Virulence Factors 288Selected Readings 289Questions 290Solving Problems in Bacterial Pathogenesis 290Special Global Perspective Problem: Integrating Concepts in Pathogenesis 291Chapter 12 Toxins and Other Toxic Virulence Factors 294Bacterial Toxins 295Transparent Mechanisms, Exciting Applications, Mysterious Purposes 295Toxin Characteristics and Nomenclature 300Nonprotein Toxins 302Peptide and Protein Exotoxins 304Toxic Effector Proteins of Specialized Secretion Systems 312Examples of Toxin-Mediated Diseases 313Diphtheria Toxin 313Clostridial Neurotoxins 319Cholera Toxin 323Toxin-Based Therapeutics and Research Tools 327Immunotoxins 327Selected Readings 329Questions 330Solving Problems in Bacterial Pathogenesis 331Chapter 13 Delivery of Virulence Factors 334Bacterial Secretion Systems and Virulence 335Common Secretory Systems 336The General Secretory (Sec) System 336The Accessory Secretory (Sec) System 336The Cotranslational Signal-Recognition Particle (SRP) System 336The Twin-Arginine Transport (TAT) System 337Secretion Systems Specific to Gram-Negative Bacteria 338Sec-Dependent Secretion Systems 338Sec-Independent Secretion Systems 341Specialized Secretion Systems Specific to Gram-Positive Bacteria 350General Secretory Transporter Systems in Gram-Positive Bacteria 350Cytolysin-Mediated Translocation (CMT) in S. pyogenes (Group A Strep) 351Type 7 Secretion System (T7SS) 352Selected Readings 353Questions 354Solving Problems in Bacterial Pathogenesis 355Chapter 14 Virulence Regulation 360Virulence Gene Regulation 361Mechanisms of Regulation 361Operons, Regulons, and Global Regulators 362Activators and Repressors 362Two-Component Regulatory Systems 364Sigma Factors 368Transcriptional Terminators and Antiterminators 369Regulation of Translation Initiation 372Regulatory Small RNAs 372Bacterial Chromatin 375Responding to Environmental Signals 376Phase Variation and Bistable Switches 376Hypermutability, Intragenomic Recombination, and Positive Selection 377Coordinate Virulence Regulation 377Quorum Sensing 378Chemotaxis 387Selected Readings 389Questions 389Solving Problems in Bacterial Pathogenesis 390Special Global Perspective Problems: Integrating Concepts in Pathogenesis 395Chapter 15 Antimicrobial Compounds and Their Targets 400Antimicrobial Compounds: The Safety Net of Modern Medicine 401The Importance of Antimicrobial Compounds 401Avoiding, Reducing, and Preventing Exposure 402Killing versus Inhibiting Growth 404Tests Used to Assess Antibiotics 404Antiseptics and Disinfectants 405Antibiotics 407Characteristics of Antibiotics 407The Process of Antibiotic Discovery 409The Economics of Antibiotic Discovery 413Mechanisms of Antibiotic Action 416Targets of Antibiotic Action 416Cell Wall Synthesis Inhibitors 417Protein Synthesis Inhibitors 422Antibiotics That Target DNA and RNA Synthesis 425Inhibitors of Tetrahydrofolate Biosynthesis 429The Newest Antibiotics 429The Newest Antibiotic Targets 430Strategies for Enhancing Antibiotic Efficacy 431The Continuing Challenge 432Selected Readings 433Questions 434Solving Problems in Bacterial Pathogenesis 435Chapter 16 Antibiotic Resistance 436The Dawning of Awareness--Uh, We Have a Problem! 437How Did We Get to Where We Are? 438And Now the Really Scary Part . . . 440Emergence and Challenge of Multidrug Resistance (MDR) 440Multiple Resistance and Genetic Linkage 441Next-Generation MDR Pathogens: The "Superbugs"! 441Mechanisms of Antibiotic Resistance 444Overview of Resistance Mechanisms 444Resistance to Antiseptics and Disinfectants 444Limiting Access of the Antibiotic 445Enzymatic Inactivation of the Antibiotic 446Modification or Protection of the Antibiotic Target 451Failure to Activate an Antibiotic 453Regulation of Resistance Genes 454Antibiotic Tolerance and Persister Cells 457Antibiotic Tolerance 457Persistence 459Toxin-Antitoxin Systems 459Horizontal Gene Transfer (HGT) of Resistance Genes 461Propagating and Maintaining Antibiotic Resistance through Selective Pressure and Changes in Fitness 463Will We Return to the Pre-Antibiotic Era? 464Returning to Status Quo or Moving Forward? 464The Hunt for Alternative Approaches to Antibiotics 466Selected Readings 468Questions 469Solving Problems in Bacterial Pathogenesis 470Special Global Perspective Problems: Integrating Concepts in Pathogenesis 470Chapter 17 Vaccination: A Critical Component of the Modern Medical Armamentarium 476Vaccines: A Major Health Care Bargain 477What Makes an Ideal Vaccine? 479Immunization Programs 480Barriers to Implementation and Success of Immunization Programs 483The Antivaccination Movement 484Vaccine Success Stories 485Subunit Vaccines 485Conjugate Vaccines 490Vaccine "Less-than-Success" Stories 492A New Age of Vaccine Development: Making Vaccines Better 494Approaches to Enhancing Immunogenicity 494Adjuvants 494Programming Adaptive Immunity 496Targeting Mucosal Immunity 500Storage of Vaccines--Strategies to Increase Shelf Life 504Passive Immunization 504Selected Readings 505Questions 505Solving Problems in Bacterial Pathogenesis 508Special Global Perspective Problems: Integrating Concepts in Pathogenesis 510Chapter 18 The Gram-Positive Opportunistic Pathogens 514What Is an Opportunist? 515Characteristics of Gram-Positive Opportunists 516Notable Gram-Positive Opportunists 516Staphylococcus aureus--Commensal Ready for a Fight 516Staphylococcus epidermidis--Accidental Pathogen 524Streptococcus pneumoniae--"Captain of All the Men of Death" 527Clostridium difficile--True Opportunist 534Other Gram-Positive Opportunists 542Selected Readings 543Questions 544Solving Problems in Bacterial Pathogenesis 544Chapter 19 The Gram-Negative Opportunistic Pathogens 548Jumping Over the (Cell) Wall: Gram-Negative Bacteria Can Be Opportunistic Pathogens Too! 549Common Traits of Gram-Negative Opportunists 549The Dark Side of Some Residents of the Human Body 550The Ever-Changing Face of E. coli 550Klebsiella pneumoniae Nosocomial Infections 554Bacteroides fragilis--The Bad Sheep of the Family 555Porphyromonas gingivalis--A Keystone Pathogen 557Environmental Inhabitants Weigh in as Opportunists 558Pseudomonas aeruginosa--A Versatile Opportunist of the Highest Order 558Burkholderia cepacia Complex--P. aeruginosa's Evil Twin 565Acinetobacter baumannii--A Deadly Threat Emerges from the Iraq War 565Don't Forget the Arthropods! 567Ehrlichia spp. 567Selected Readings 568Questions 569Solving Problems in Bacterial Pathogenesis 569Special Global Perspective Problems: Integrating Concepts in Pathogenesis 570Chapter 20 The Changing Roles of Microbiologists in an Age of Bioterrorism and Emerging Diseases 574When Microbiologists Are Called to the Front Line 575Tracking Down a Bioterrorist 576Unintentional or Deliberate? 577Timing 579Tracing the Source 579Lessons Learned 579The "Top Four" Bioterror Agents 582Bacillus anthracis Spores 582Smallpox 583Yersinia pestis 583Botulinum Neurotoxin 584What If Bioterrorists Hit Us with Something Completely New? 585Biosecurity in a Complex, Dynamic, and Ever-Changing World 585Food Safety and Biosecurity 586The Case for Food Irradiation 587The Future of Biosecurity 589Selected Readings 589Questions 590Solving Problems in Bacterial Pathogenesis 591Glossary 593Index 661

O autorze

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.