Читать книгу Bacterial Pathogenesis - Brenda A. Wilson - Страница 6
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CHAPTER 1 The Power of Bacteria
Why Are Bacteria So Much in the Public Health Spotlight Nowadays?
Bacteria, a Formidable Ancient Life Form
Pressing Current Infectious Disease Issues
Emerging and Reemerging Infectious Diseases
Foodborne and Waterborne Infections
Modern Medicine as a Source of New Diseases
Postsurgical and Other Wound Infections
Surveillance: An Early Warning System
Making Hospitals Safe for Patients
And Now for Some Good News: You’ve Got a Bacterial Infection!
The Helicobacter pylori Revolution
A Brave New World of Pathogenesis Research
Insights into Pathogen Evolution
Modeling the Host-Pathogen Interaction in Experimental Animals
CHAPTER 2 Skin and Mucosa: The First Lines of Defense against Bacterial Infections
The Best Defense: Avoid, Reduce, and Prevent Exposure!
Barriers: Skin and Mucosal Membranes
The Layers of Cells That Protect the Body
Normal Microbiota of the Skin and Mucosa
Special Defenses of the Gastrointestinal Tract
Special Defenses of the Urogenital Tract
Special Defenses of the Respiratory Tract
Immune Defenses of the Skin and Mucosa
Models for Studying Breaches of Barrier Defenses
CHAPTER 3 The Innate Immune System: Always on Guard
Triggering Innate Immune Defenses
Innate Immune Cells That Defend Blood and Tissue
Monocytes, Macrophages, and Dendritic Cells (DCs)
Granulocytes: Basophils, Mast Cells, and Eosinophils
Transmigration—How Do Phagocytes Know When and Where to Go?
How Phagocytes Recognize and Respond to Bacteria
Oxidative Burst in Phagolysosomes
Autophagy—Another Pathway for the Killing of Intracellular Pathogens
Overview of Complement Pathways and Their Function
Steps in Complement Activation
Controlling Complement Activation
Cytokines and Chemokines—Mediators of Immune Responses
Roles of Cytokines and Chemokines in Directing Innate Immune Responses
Inflammation and Collateral Damage
Septic Shock: The Dark Side of the Innate Defenses
Other Innate Defenses of the Body—Nutritional Immunity
CHAPTER 4 The Adaptive Defenses: Antibodies and Cytotoxic T Cells
The Specialists: Adapting to a Particular Pathogen Challenge
B Cells: Producers of Antibodies
The Humoral (Antibody) Immune Response
Characteristics of Antibodies and Their Diverse Roles in Preventing Infection
Secretory Antibodies: Antibodies That Protect Mucosal Surfaces
Pathogen and Toxin Neutralization by Antibodies
Cytotoxic T Cells, Also Known as Cytotoxic T Lymphocytes (CTLs)
Cytotoxic T Lymphocytes: Critical Defense against Intracellular Pathogens
Antigen Presentation to the Immune System
Processing of Protein Antigens by Dendritic Cells
Interaction between APCs and T Cells: The T-Cell-Dependent Response
Th-(Th1/Th2/Th17)-Cell-Mediated Immunity
Production of Antibodies by B Cells
Links between the Innate and Adaptive Defense Systems
T-Cell-Independent Antibody Responses
Mucosal Immunity: IgA/sIgA Antibodies
Development of the Adaptive Immune System from Infancy to Adulthood
Adaptive Defense Systems in Nonmammals
The Dark Side of the Adaptive Defenses: Autoimmune Disease
Solving Problems in Bacterial Pathogenesis
CHAPTER 5 The Microbiota of the Human Body: Microbiomes and Beyond
Importance of the Normal Resident Microbial Populations (Microbiota) of the Human Body
Characterization of the Body’s Microbiota
Taking a Microbial Census by Using Microbial rRNA Gene Sequence Analysis
Characterizing Microbiomes by Using Metagenomic Analysis
Overview of the Human Microbiota
Microbiota of the Small Intestine and Colon
Microbiota of the Vaginal Tract
The Other Microbiota: The Forgotten Eukaryotes
Solving Problems in Bacterial Pathogenesis
CHAPTER 6 Microbes and Disease: Establishing a Connection
History and Relevance of Koch’s Postulates
Koch’s Postulates: A Set of Criteria Used To Establish a Microbe-Disease Connection
Challenges to Satisfying Koch’s Postulates
The First Postulate: Association of the Microbe with Lesions of the Disease
The Second Postulate: Isolating the Bacterium in Pure Culture
The Fourth Postulate: Reisolating the Bacterium from the Intentionally Infected Animal
Modern Alternatives To Satisfy Koch’s Postulates
Detecting the Presence of the Pathogen Only in Diseased Tissues
Eliminate the Pathogen and Prevent or Cure the Disease
Comparative Infectious Disease Causation
The Microbiota Shift Disease Problem
Koch’s Postulates and Pathogenic Microbial Communities
Keystone Pathogens and Microbial Shift Diseases
Varieties of Human-Microbe Interactions
Views of the Human-Microbe Interaction
Virulence as a Complex Phenomenon
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 7 Mechanisms of Genetic Modification and Exchange: Role in Pathogen Evolution
Adapt or Perish
Acquiring New Virulence Traits by Horizontal Gene Transfer
Mechanisms of Genetic Change and Diversification
Spontaneous Mutation
Phase Variation
Antigenic Variation
Horizontal Gene Transfer: Mobile Genetic Elements
Natural Transformation
Conjugation: Plasmids and Transposons
Phage Transduction
Control of Horizontal Gene Transfer
Toxin-Antitoxin Systems—Retaining the Goods
Restriction-Modification Systems—Bacterial Innate Immunity from Foreign DNA
CRISPR-Cas Systems—Bacterial Adaptive Immunity from Foreign DNA
Type 6 Secretion Systems—Bacterial Defense Against Conjugation
Pathogenicity Islands and Pathogen Evolution
Properties of Pathogenicity Islands
Pathogen Evolution in Quantum Leaps
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 8 Identification of Virulence Factors: Measuring Infectivity and Virulence
How Does One Experimentally Measure Virulence and Satisfy Koch’s Postulates?
Animal Models of Infection
Human Volunteers
Nonhuman Animal Models
Measuring Bacterial Infection in Animal Models
Ethical Considerations
Animal Model Basics
Survival Curve Analysis and Biophotonic Imaging
ID50 and LD50 Values
Competition Assays
Tissue Culture and Organ Culture Models
Tissue Culture Models
Gentamicin Protection Assay for Cell Adhesion and Invasion
Plaque Assay for Intracellular Survival and Cell-to-Cell Spread
Fluorescence Microscopy Techniques for Assessing Effects of Pathogens on Host Cells
Organ Culture Models
The Continuing Need for Reliable and Plentiful Information about Disease Pathology
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 9 Identification of Virulence Factors: Molecular Approaches for Bacterial Factors
Finding a Needle in a Haystack
Biochemical Approaches
Isolation and Purification of Toxic Factors
Molecular Genetic Approaches
Screening Using Recombinant Genes
Reporter Fusions
Mutagenesis Screening
Genome-wide Sequencing Approaches for Identifying Virulence Genes
Tn-Seq Technology to Identify In Vivo-Expressed Genes
RNA-Seq Technology to Identify In Vivo-Expressed Genes
Comparative Genomic Sequence Analysis for Identifying Virulence Genes
Proteomics Approaches for Identifying Virulence Factors
Protein Microarrays (Proteoarrays)
In Vivo-Induced Antigen Technology (IVIAT)
The Importance of Understanding Bacterial Physiology
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 10 Identification of Virulence Factors: Molecular Approaches for Host Factors
Comparative Approaches to Identify Host Factors Required for Infection
Transgenic Animal Models
In vivo Imaging of Animals during Infection
Systems Genetics: Comparative Genomics of the Host Response
Screening Approaches to Identify Host Factors Required for Infection
Genome-Wide Screening
Host Response Profiling to Identify Host Factors Required for Infection
Transcriptomics
Proteomics
Metabolomics
The Promise and the Caution
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 11 Bacterial Strategies for Colonization and Survival in the Host
What Does Not Kill You Makes You Stronger—Or, a Better Pathogen
Preinfection
Survival in the External Environment
Biofilms
Motility and Chemotaxis
Colonization of Host Surfaces
Penetrating Intact Skin
Penetrating the Mucin Layer
Evading the Host’s Innate Immunity
Nutrient and Iron Acquisition Mechanisms
Adherence
Evading the Host Immune Response
Avoiding Complement and Phagocytosis
Invasion and Uptake by Host Cells
Surviving Phagocytosis
Cell-to-Cell Spread
Tissue Penetration and Dissemination
Beyond Virulence Factors
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
Special Global Perspective Problem: Integrating Concepts in Pathogenesis
CHAPTER 12 Toxins and Other Toxic Virulence Factors
Bacterial Toxins
Transparent Mechanisms, Exciting Applications, Mysterious Purposes
Toxin Characteristics and Nomenclature
Nonprotein Toxins
Peptide and Protein Exotoxins
Toxic Effector Proteins of Specialized Secretion Systems
Examples of Toxin-Mediated Diseases
Diphtheria Toxin
Clostridial Neurotoxins
Cholera Toxin
Toxin-Based Therapeutics and Research Tools
Immunotoxins
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 13 Delivery of Virulence Factors
Bacterial Secretion Systems and Virulence
Common Secretory Systems
The General Secretory (Sec) System
The Accessory Secretory (Sec) System
The Cotranslational Signal-Recognition Particle (SRP) System
The Twin-Arginine Transport (TAT) System
Secretion Systems Specific to Gram-Negative Bacteria
Sec-Dependent Secretion Systems
Sec-Independent Secretion Systems
Specialized Secretion Systems Specific to Gram-Positive Bacteria
General Secretory Transporter Systems in Gram-Positive Bacteria
Cytolysin-Mediated Translocation (CMT) in S. pyogenes (Group A Strep)
Type 7 Secretion System (T7SS)
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 14 Virulence Regulation
Virulence Gene Regulation
Mechanisms of Regulation
Operons, Regulons, and Global Regulators
Activators and Repressors
Two-Component Regulatory Systems
Sigma Factors
Transcriptional Terminators and Antiterminators
Regulation of Translation Initiation
Regulatory Small RNAs
Bacterial Chromatin
Responding to Environmental Signals
Phase Variation and Bistable Switches
Hypermutability, Intragenomic Recombination, and Positive Selection
Coordinate Virulence Regulation
Quorum Sensing
Chemotaxis
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
Special Global Perspective Problems: Integrating Concepts in Pathogenesis
CHAPTER 15 Antimicrobial Compounds and Their Targets
Antimicrobial Compounds: The Safety Net of Modern Medicine
The Importance of Antimicrobial Compounds
Avoiding, Reducing, and Preventing Exposure
Killing versus Inhibiting Growth
Tests Used To Assess Antibiotics
Antiseptics and Disinfectants
Antibiotics
Characteristics of Antibiotics
The Process of Antibiotic Discovery
The Economics of Antibiotic Discovery
Mechanisms of Antibiotic Action
Targets of Antibiotic Action
Cell Wall Synthesis Inhibitors
Protein Synthesis Inhibitors
Antibiotics That Target DNA and RNA Synthesis
Inhibitors of Tetrahydrofolate Biosynthesis
The Newest Antibiotics
The Newest Antibiotic Targets
Strategies for Enhancing Antibiotic Efficacy
The Continuing Challenge
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 16 Antibiotic Resistance
The Dawning of Awareness—Uh, We Have a Problem!
How Did We Get to Where We Are?
And Now the Really Scary Part …
Emergence and Challenge of Multidrug Resistance (MDR)
Multiple Resistance and Genetic Linkage
Next-Generation MDR Pathogens: The “Superbugs”!
Mechanisms of Antibiotic Resistance
Overview of Resistance Mechanisms
Resistance to Antiseptics and Disinfectants
Limiting Access of the Antibiotic
Enzymatic Inactivation of the Antibiotic
Modification or Protection of the Antibiotic Target
Failure to Activate an Antibiotic
Regulation of Resistance Genes
Antibiotic Tolerance and Persister Cells
Antibiotic Tolerance
Persistence
Toxin-Antitoxin Systems
Horizontal Gene Transfer (HGT) of Resistance Genes
Propagating and Maintaining Antibiotic Resistance through Selective Pressure and Changes in Fitness
Will We Return to the Pre-Antibiotic Era?
Returning to Status Quo or Moving Forward?
The Hunt for Alternative Approaches to Antibiotics
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
Special Global Perspective Problems: Integrating Concepts in Pathogenesis
CHAPTER 17 Vaccination: A Critical Component of the Modern Medical Armamentarium
Vaccines: A Major Health Care Bargain
What Makes an Ideal Vaccine?
Immunization Programs
Barriers to Implementation and Success of Immunization Programs
The Antivaccination Movement
Vaccine Success Stories
Subunit Vaccines
Conjugate Vaccines
Vaccine “Less-than-Success” Stories
A New Age of Vaccine Development: Making Vaccines Better
Approaches to Enhancing Immunogenicity
Adjuvants
Programming Adaptive Immunity
Targeting Mucosal Immunity
Storage of Vaccines—Strategies to Increase Shelf Life
Passive Immunization
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
Special Global Perspective Problems: Integrating Concepts in Pathogenesis
CHAPTER 18 The Gram-Positive Opportunistic Pathogens
What Is an Opportunist?
Characteristics of Gram-Positive Opportunists
Notable Gram-Positive Opportunists
Staphylococcus aureus—Commensal Ready for a Fight
Staphylococcus epidermidis—Accidental Pathogen
Streptococcus pneumoniae—“Captain of All the Men of Death”
Clostridium difficile—True Opportunist
Other Gram-Positive Opportunists
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
CHAPTER 19 The Gram-Negative Opportunistic Pathogens
Jumping Over the (Cell) Wall: Gram-Negative Bacteria Can Be Opportunistic Pathogens Too!
Common Traits of Gram-Negative Opportunists
The Dark Side of Some Residents of the Human Body
The Ever-Changing Face of E. coli
Klebsiella pneumoniae Nosocomial Infections
Bacteroides fragilis—The Bad Sheep of the Family
Porphyromonas gingivalis—A Keystone Pathogen
Environmental Inhabitants Weigh in as Opportunists
Pseudomonas aeruginosa—A Versatile Opportunist of the Highest Order
Burkholderia cepacia Complex—P. aeruginosa’s Evil Twin
Acinetobacter baumannii—A Deadly Threat Emerges from the Iraq War
Don’t Forget the Arthropods!
Ehrlichia spp.
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
Special Global Perspective Problems: Integrating Concepts in Pathogenesis
CHAPTER 20 The Changing Roles of Microbiologists in an Age of Bioterrorism and Emerging Diseases
When Microbiologists Are Called to the Front Line
Tracking Down a Bioterrorist
Unintentional or Deliberate?
Timing
Tracing the Source
Lessons Learned
The “Top Four” Bioterror Agents
Bacillus anthracis Spores
Smallpox
Yersinia pestis
Botulinum Neurotoxin
What If Bioterrorists Hit Us with Something Completely New?
Biosecurity in a Complex, Dynamic, and Ever-Changing World
Food Safety and Biosecurity
The Case for Food Irradiation
The Future of Biosecurity
Selected Readings
Questions
Solving Problems in Bacterial Pathogenesis
