Brenda A. Wilson - Bacterial Pathogenesis

Adaptive Defense Systems in Nonmammals

The Dark Side of the Adaptive Defenses: Autoimmune Disease

Selected Readings

Questions

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

Beyond the Metagenome

Overview of the Human Microbiota

Skin Microbiota

Oropharyngeal Microbiota

Microbiota of the Small Intestine and Colon

Microbiota of the Vaginal Tract

The Other Microbiota: The Forgotten Eukaryotes

Selected Readings

Questions

Solving Problems in Bacterial Pathogenesis

CHAPTER 6 Microbes and Disease: Establishing a Connection

History and Relevance of Koch’s Postulates

Early Germ Theory

Koch’s Postulates: A Set of Criteria Used To Establish a Microbe-Disease Connection

Challenges to Satisfying Koch’s Postulates

Easier Said than Done …

The First Postulate: Association of the Microbe with Lesions of the Disease

The Second Postulate: Isolating the Bacterium in Pure Culture

The Third Postulate: Showing that the Isolated Bacterium Causes Disease Experimentally in Humans or Animals

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

Molecular Koch’s Postulates

Concepts of Disease

Varieties of Human-Microbe Interactions

Views of the Human-Microbe Interaction

Virulence as a Complex Phenomenon

Selected Readings

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)