Bacteriophages: Biology, Technology, Therapy

✍ Scribed by Stephen T. Abedon, Benjamin H. Burrowes, Malcolm L. McConville, David R. Harper

• Publisher: Springer
• Year: 2018
• Tongue: English
• Leaves: 1200
• Category: Library

✦ Table of Contents

Preface
Contents
About the Editors
Contributors
Part I: Introduction to Bacteriophages: Biology, Technology, Therapy
Introduction to Bacteriophages
Bacteriophages
On the Nature of Bacteriophages
Antibiotics: From Savior to Crisis
Antibiotics: A Biological Approach
References
Part II: Bacteriophage Biology
Structure and Function of Bacteriophages
Introduction
Overview of Phage Families
The Leviviridae Family of Single-Stranded RNA Phages
Assembly
Structure
The Microviridae Family of Single-Stranded DNA Phages
Assembly
Structure
The Inoviridae Family of Filamentous, Single-Stranded DNA Phages
Assembly
Structure
The Cystoviridae Family of Double-Stranded RNA Phages
Assembly
Structure
Overview of Bacteriophages Containing Double-Stranded DNA Genomes
The Tectiviridae Family
Assembly
Structure
The Corticoviridae Family
Assembly
Structure
Overview of Order Caudovirales
Caudovirales Head Assembly
Caudovirales Head Structure
Podoviridae Tail Assembly and Structure
Siphoviridae Tail Assembly
Siphoviridae Tail Structure
Myoviridae Tail Assembly
Myoviridae Tail Structure
Conclusions and Perspectives
Cross-References
References
Adsorption: Phage Acquisition of Bacteria
Introduction
Free Virions to Virocells
Movement of Free Phages
Virion Diffusion
Non-diffusive Movement
Encounter
Attachment
Overview
Adsorption Factors and Reversible Attachment
Irreversible Attachment
Adsorption Kinetics
Importance of Phage Titers
Adsorption Rate Constants
How Fast Adsorption Is Fast Enough?
Adsorption Rate Constant Determination
Genome Translocation
Conclusion
Cross-References
References
Temperate Phages, Prophages, and Lysogeny
Introduction
Lysogeny and Lysogenic Cycles
Stably Associating with Host Bacteria
Benefiting the Lysogen
Lysis-Lysogeny Decisions
Induction
Immunity
Lysogenic Conversion and Morons
Bacteriophage Lambda
The Lysogeny Decision
Lambda and Lambdoid Genomes
Prophages P2 and P2-Likes
P2 Virion and Genome
P2 Lysogeny
Temperate Phages of Staphylococci and Streptococci
Staphylococcal Phages
Morphological Families and Classification
Streptococcal Phages
Morphological Families and Classification
Role of Prophages in Modulation of Bacterial Host Biology and Evolution
Toxins and Virulence Factors Encoded by Prophages
Staphylococcus aureus
Clostridium botulinum
Vibrio cholerae
Corynebacterium diphtheriae
Streptococcus pyogenes
Conclusions
References
Bacteriophage-Mediated Horizontal Gene Transfer: Transduction
Introduction
Overview of Transduction
Historical Perspectives on Horizontal Gene Transfer in Bacteria
The Discovery of Transformation
The Discovery of Conjugation
The Discovery of Transduction
Examples of Transducing Phages
Bacteriophage P1
Bacteriophage P22
Lambda (λ)
Mu
Phage Features Important for Transduction
Host DNA Degradation
DNA Packaging Method
Mobile Genetic Elements Within Phage Genomes
Integration Site Specificity
Examples of Transduction Hijackers
Gene Transfer Agents
Phage-Inducible Chromosomal Islands
Methods to Detect and Characterize Transducing Particles
Phenotypic Changes of the Bacterial Host
Phenotypic Changes of the Transducing Particle
Genotypic Changes of the Bacterial Host
Genotypic Changes of the Transducing Particle
Potential Risks to Human Health Posed by Transduction
Transduction and the Spread of Antibiotic Resistance Genes
Transduction and the Implications to Phage Therapy
Conclusions
Cross-References
References
Genetics and Genomics of Bacteriophages
Introduction
The Nature of Bacteriophage Genomes: Evolution and Mosaicism
Main Structural Features
Structural Components of Tailed Bacteriophages
Structural Components of PFP Bacteriophages
Bacteriophage T4
Hallmark Genes and Variability
Hallmark Genes and Bacteriophage Evolution
Comparative Genomics
Bacterial Comparative Genomics: The Impact of Bacteriophages
Comparative Genomics of Bacteriophages: Phylogeny and Evolution
Comparative Genomics and Bacteriophage Taxonomy
Comparative Metagenomics
Functional Genomics
Functional Genomics and Genetic Characterization
Site-Directed Mutagenesis (SDM) and Gene Knockouts
Transcriptomics
Host Response to Bacteriophage Infection
Discussion and Future Perspectives
References
Bacteriophage Discovery and Genomics
Introduction
Phage Discovery and Genomics as a Platform for Science Education
The Phage Hunters Integrating Research and Education (PHIRE) Program
The Mycobacterial Genetics Course
The Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) Program
A View of Bacteriophage Genetic Diversity
Concluding Remarks
Cross-References
References
Bacteria-Phage Antagonistic Coevolution and the Implications for Phage Therapy
The Coevolutionary Process and the Red Queen´s Race
Experimental Studies of Bacteria-Bacteriophage Antagonistic Coevolution
Mechanisms of Bacterial Resistance to Lytic Bacteriophage and Phage Counter-Resistance
Effects of Resistance and Counter-Resistance on Fitness and Phenotype
(Co)Evolutionary Considerations of Phage Therapy
Cross-References
References
Bacteriophage Ecology
Introduction
Phage Presence in Nature
Viable Phage Counts
Phage Total Counts
Nucleic Acid Sequence-Based Determinations
Linking Phages to Bacteria via Metagenomics
Biogeography
Phage Prevalence Within Environments
Phage Movement
Phage Distributions Within Environments
Phage Population Ecology
Phage Life Cycles as Ecological Phenomena
Virion Durability
Virion Attachment Affinity
Evasion of Host Defenses
Phage Latent Periods
Phage Burst Size
Phage Community Ecology
Predators, Parasites, or Parasitoids?
Killing the Winner
Phage Exploitation of Biofilm-Associated Bacteria
Phage Ecosystem Ecology
Summary
Cross-References
References
Bacteriophage Pharmacology and Immunology
Introduction
Safety Considerations in Phage Choice for Phage Therapy
Avoiding Temperate Phages
Avoiding Phages Encoding Virulence Factors
Avoiding Transducing Phages
Summary: Safety Considerations
Phage Therapy Pharmacology Basics
Pharmacokinetics and Pharmacodynamics
Pharmacokinetics in More Detail
Conceptualizing Pharmacology
Passive Treatment Versus Active Treatment
Passive Phage Therapy
Active Penetration
Active Phage Therapy
Summarizing Phage Therapy Pharmacological Phenomena
Phage Interactions with Immune Systems
Overview of Immunity
Adaptive Immunity
Innate Immunity
Effects of Immune Response on Phage Pharmacokinetics
Relation of Immune Response to Phage Pharmacodynamics
Conclusion
Cross-References
References
Phage Infection and Lysis
Introduction
Productive, Reductive, and Destructive Phage Infections
Phage-Productive Infections
Phage-Reductive Infections
Phage-Destructive Infections
Phage Growth Parameters
Latent Periods
Burst Sizes
Utility for Phage Therapy
Strictly Lytic Phages for Phage Therapy
Infection
The Eclipse
Phage Gene Expression
Phage Genomes and Replication
The Latent Period Continues. . .
. . .And Continues?
The Rise
Host Physiology Considerations
Virion Release
Holin-Mediated Lysis from Within
Lysis-Mediating Phage Proteins
Antiholins
Inhibition of Peptidoglycan Production
Chronic Release
Determination of Phage Growth Parameter Values
Virion Durability Determination
Eclipse, Latent Period, Burst Size, and Rise
Phage Population Growth Rates
Continuous Culture
Plaques
Conclusion
Cross-References
References
Part III: History of Bacteriophages
The Discovery of Bacteriophages and the Historical Context
Discovery in Science: No Eureka Moment
Microbes Before Twort and d´Herelle
Viruses
Filters
Fact Making´´: Bacterial Lysis andLytic Principles´´
Cultures, Cells, Microbial Mutations
Twort and d´Herelle: The Canonical Account
The Canonical History of Bacteriophage
Becoming Phage: 1920-1940
Phage Discovery Completed
Discovery and Priority Revisited
Cross-References
References
Early Therapeutic and Prophylactic Uses of Bacteriophages
Introduction: A Brief History
Phage Therapy for Wound Treatment, Surgery, and Dermatology
Phage Therapy for Treatment of Enteric Infections
Prophylactic Use of Phages
Intravenous Staphylococcal Bacteriophage: The Highest Achievement of the Georgian Scientists
Conclusions
References
Part IV: Bacteriophage Technology
Isolation of Bacteriophages
Glossary
Introduction
Basic Phage Isolation Techniques
Biases in Isolation
Spot Testing
Increasing Phage Concentrations
Generation of Pure Isolates and Phage Stocks
Storing Isolated Phages
Where to Hunt for Phages
Isolation from the Environment
Common Sources for Isolation of Therapeutic Phages
Isolation from Lysogens
Isolation from Diverse Environments
Resulting Phage Phenotypes
Altered Procedures and Their Effect on Host Range
Plaque Morphology Indicates Diverse Phage Characteristics
Phage Isolation for Biotechnology
Implications for the Use of Phages as Antimicrobials
High-Throughput (HTP) Phage Isolation
Conclusions
Cross-References
References
Bacteriophage Use in Molecular Biology and Biotechnology
Early Contributions to Molecular Biology
Early Studies of Phage Chemical Composition and Physical Structure
Spontaneous Mutation and Heredity
Phage Growth and Plaque Formation
Phage Typing
Phage Amplification and MALDI-TOF MS for Bacterial Identification
The Discovery of Lysogeny and Prophages
The First Unequivocal Demonstration of Lysogeny
The Discovery of Phage λ and the Beginning of Prophage Genome Mapping
The Discovery of Phage P1 Used in Bacterial Transduction
The Discovery of Site-Specific Recombination and Its Applications
The Campbell Model of Phage Integration
The Determination of Attachment Sites on Host and Phage DNA Molecules
The Development of Site-Specific Integrating Plasmids
Discovery of the Cre/LoxP System in Phage P1
Applications of the Cre/Lox System in Genetically Engineered Mice
Discovery of Bacterial DNA Restriction and Modification Systems
Discovery of the Restriction/Modification Phenomenon
Discovery of the Role of Methylation in Restriction/Modification
The First Identification of a Specific Restriction Site in Bacterial DNA
The Development of Molecular Cloning
The Development of Restriction Mapping
The Discovery of Viral Metabolic Products
The Discovery of Thymineless Death and Its Implications for Chemotherapy Research
The Role of Phages in Understanding Gene Structure, Expression, and Regulation
Luria and Delbruck´s ``Fluctuation Test´´ Shows That Spontaneous Mutations Occur in Bacterial Genes
Hershey and Chase Demonstrate That DNA Is the Hereditary Material
Benzer Maps the Fine Structure of Genes in the Phage T4 rII Region
The Discovery that Messenger RNA Is a Direct Product of Genes
The Determination of the Genetic Code
The First Observation of Gene Regulation Due to a Repressor Factor (The PaJaMo Experiment)
The First Isolation and Characterization of a Repressor Factor Involved in Gene Regulation
Isolation of the ρ Termination Factor and Characterization of Termination/Antitermination in λ
The Construction of a Synthetic Genetic Regulatory Circuit that Exhibits Complex Behavior
Refactoring Phages to Learn About Complex Genetic Regulatory Circuits at the Organismal Level
Conclusion
Systems Biology
Evolution
Ecology
Cross-References
References
Detection of Bacteriophages: Phage Plaques
Introduction
Plaques
Initiating Plaques
Bacterial Lawns, Plaques, and Spots
Plaque-Forming Units
Too Many or Too Few Plaques
Plaques Versus Spots
Plaque Formation
Phage Clumped Dispersion
Bacterial Clumped Dispersion
Plaque Size
Plaque-Based Phage Characterization
Efficiency of Plating
Efficiency of Center of Infection
Mixed-Indicator Technique
Conclusions
References
Detection of Bacteriophages: Statistical Aspects of Plaque Assay
Introduction
Overview
TFTC and TNTC
Spot Counts Versus Plate Counts
Number of Repeats
Utility of Trimmed Means
Number of Dilution Series
Utility of Larger Volumes
When Comparisons Matter
Conclusions
Cross-References
References
Detection of Bacteriophages: Electron Microscopy and Visualization
Introduction
Electron Microscopy
Initial Electron Microscopy of Phages
Staining
Metal Shadowing
Negative Staining
Thin-Sectioning, Room-Temperature and Cryogenic
Frozen-Hydrated Specimens, Unstained and Negatively Stained
Scanning Electron and Helium-Ion Microscopy
Scanning Transmission Electron Microscopy, Dark-Field
In Situ, Liquid-Cell Electron Microscopy
Analytical Electron Microscopy
Two-Dimensional Image Averaging and Diffraction
Three Dimensions from Two
Immuno-EM
Conclusion
References
Detection of Bacteriophages: Sequence-Based Systems
Introduction
Overview of Sequencing Methods
Short-Read Platforms
Long-Read Platforms
A Note on Sequence Data and Sharing
Applications of Sequencing-Based Detection Methods
Gene-Based Detection of Bacteriophages
Cyanophages
T4-Like Phages
T7-Like Phages
Gokushoviruses
Other Potential Signature Genes
Genome Sequencing
Sequence-Based Identification of Prophages
Metagenomics-Based Detection of Bacteriophages
Conclusions
Cross-References
References
Novel Approaches for Detection of Bacteriophage
Mass Spectrometry
Raman Spectroscopy
Summary
Cross-References
References
Bacteriophages in Nanotechnology: History and Future
Introduction
Bacteriophage Capsids
Phage Virions and Phage Proteins in Biosensors
Attachment of Whole, Non-modified Virions
Attachment of Phage Proteins
Signal Transduction Methods
Phage Display
Phages in Nanostructured Materials
Applications Using Whole Phages
Applications Using Phage Display-Generated Peptides or Proteins
Whole Phage in Structured Materials
Phage Catalysts
Phages as Drug Delivery Carriers
Phage-Containing Antibacterial Materials
Challenges to Commercialization
Conclusion
Glossary
References
The Selection and Optimization of Phage Hosts
Introduction
Phage Propagation
Surrogate Hosts
Prophages
Reducing Host Toxicity
Endotoxin
Conclusion
References
Bacteriophage Manufacturing: From Early Twentieth-Century Processes to Current GMP
What Is GMP, and When Is It Needed?
Definition of GMP
History of GMP Guidelines, Need, Definition, and Place of Bacteriophage
Evolution of GMP: Current Guidelines and Discrepancies Between Regions
History of Phage Production. How It Was Handled Until Now
Applying GMP to Bacteriophages
General Considerations
Cell Culture Media AOF, No Animal, or Human-Origin Material
Biological Material Choice
Phage Banking
Cell Banking
Manufacturing
Why Prefer Single Use to Stainless Steel?
Upstream Process: Phage Production
Downstream Process: Phage Purification
Formulation, Fill, and Finish
Control Quality
Cell Substrate Quality Control
Bacteriophage QC
Phage Host Range
Host Cell Protein
Endotoxins and Pyrogens
Transmission Electron Microscopy
Genome Sequence
RFLP (Restriction Fragment Length Polymorphism)
RAPD (Random Amplified Polymorphic DNA)
Phage DS Infectious Titer
Stability Studies
Future of the Regulation for Phage-Based Drug Products
Perspectives of Phage Manufacturing
Impact of GMO Phage Manufacturing
Perspective About Phage Quality Control
Conclusion
Cross-References
Glossary
References
Intellectual Property Issues for Bacteriophages
Patents and Patenting
What Is a Patent?
Why Apply for a Patent?
Patentability and Freedom-to-Operate Assessments
What Is Needed to Apply for a Patent?
Novelty, Inventive Step, and the Undue Burden
Unity of the Invention
Elements of a Typical Patent Application
From Filing to Grant
After Award
Timing and Patent Terms
First to File Versus First to Invent
Safe Harbors and Extinct Submarines
Future Developments
Patenting of Bacteriophages
Patenting Natural (Unmodified) Bacteriophages
Patenting Genetically Modified Bacteriophages
Patenting Novel Processes or Technologies
Bacteriophage Patents
Accessing Bacteriophage Patents Online
Glossary
References
Bacteriophage as Biocontrol Agents
Introduction
Biological Control
Bacteriophages in Nontherapeutic Biological Control
Efficacy of Biological Control
The Damage Threshold: A Biocontrol Concept
IPM
The Kinetics of Biological Control
Implications for Clinical Trials
Nature of the Agent
Summary
Cross-References
Glossary
References
Part V: Agriculture, Food, and Environmental Use of Bacteriophages
Bacteriophages as Bio-sanitizers in Food Production and Healthcare Settings
Introduction
Phages as Bio-sanitizers on Food Contact Surfaces
Phages as Bio-sanitizers for Listeria monocytogenes
Phages as Bio-sanitizers for Other Foodborne Pathogens
Escherichia Coli O157:H7
Salmonella spp.
Phages as Bio-sanitizers in Hospital Settings
Phage Components as Bio-sanitizers or Sanitizing Adjuncts
Phage Application Approaches
Conclusion and Future Directions
References
Biofilm Applications of Bacteriophages
Applications of Bacteriophages to Biofilms and Surface-Attached Bacteria
Introduction
Biofilms in Food Industrial Settings
Prevalence of Biofilms
Biofilm Formation on Surfaces
Impact of Biofilms in Different Food Industry Settings
Dairy Industry
Poultry Industry
Red Meat Industry
Seafood Industry
Fresh Fruit and Vegetable Industry
Currently Used Removal Strategies
Bacteriophage Application to Biofilms and Other Surface-Attached Bacteria Formed in the Food Industry
Application of Bacteriophages to Equipment Surfaces and to Working Surfaces and to Enhance Equipment Performance
Application of Bacteriophages to Foods
Fresh-Cut Fruits and Vegetables
Red and Poultry Meats
Dairy Products
Single Bacteriophage Versus Cocktail Approach and Other Approaches
Challenges that Bacteriophages Face in Industrial Environments
Bacteriophages and Biofilms in the Clinical Setting
Background
Bacteriophage-Biofilm Interactions
Applications
Conclusion
Cross-References
References
Industrial Processes Involving Bacteriophages
Introduction
Highly Complex Bacterial Culture-Driven Bioprocesses
Bioprocesses Driven by Well Defined, Mixed Cultures
Monocultures in Industrial Biotechnology: Pharmaceutical Catalysts, Bacterial Biomass, and Green Chemistry
Pharmaceutical Bioprocesses
Phage Growth in Bioprocesses
Prophages in Bioprocesses
Bacteriophage Contamination Troubleshooting and Prevention
Bacteriophages as Antibacterials in Bioprocesses
Conclusions
Cross-References
References
Crop Use of Bacteriophages
Management of Plant Bacterial Diseases
Use of Bacteriophages in Agriculture
Factors that Challenge Use of Phages
Bacteriophages and the Bacterial Carrier System
Phage as Infectious Bacteriostatic Particles
Application Challenges in Agriculture
Historical Perspective on the Phage Delivery System
Avoidance of Host Resistance and Other Considerations
Field Application of Carrier-Phage
Cross-References
References
Food Safety
Introduction
Food and Microorganisms
Limiting Food Contamination
Food Legislation Enhances Safety
Trends Towards Industrialized Convenience Foods
Bacteriophages and Food Safety
Bacteriophages for the Biological Control of Gram-Negative Bacteria
Treatment of Poultry by Campylobacteriophage
Control of Salmonella enterica Using Bacteriophage
Bacteriophage for the Control of Escherichia coli
Phages Infecting Yersinia enterocolitica
Cronobacter sakazakii
Pseudomonas aeruginosa
Legionella pneumophila
Vibrio parahaemolyticus
Control of Gram-Positive Bacteria by Bacteriophage Treatment
Listeriophages Are Well Suited for Biocontrol
Bacteriophages for the Control of Staphylococcus aureus
Control of Bacillus cereus in Food
Future Perspectives
Conclusion
Glossary
References
Bacteriophage Utilization in Animal Hygiene
Introduction
Brief History of Phage Use in Animal Hygiene
Live Animal Pathogen Reduction Treatments
Phages as a Strategy to Improve Hygiene in Live Animals
Challenges to Phage Treatment of Live Animals
Poultry Specific Issues and Phage Usage
Poultry Health
Swine Specific Issues and Phage Usage
Swine Health
Ruminant Specific Issues and Phage Usage
Hide-Specific Spray Treatments for Cattle
Cattle Health
Conclusions and the Future
Cross-References
References
Part VI: Therapeutic Use of Bacteriophages
Current Updates from the Long-Standing Phage Research Centers in Georgia, Poland, and Russia
Introduction
Current Status of Georgian Research
History
Spin-Off Entities
International Collaboration
Targeting Antibiotic-Resistant Bacteria
Treatment of Cystic Fibrosis-Associated Infections
Treatment of Urinary Tract Infections
Targeting Infected Wounds
Conclusions: Georgian Phage Therapy
Current Status of Polish Research
The Hirszfeld Institute
Progress of the Phage Therapy Unit 2012-2017
Immunological Responses to Phages
The Hirszfeld Institute´s Phage Collection
Plasmid-Prophage-Free Hosts for Optimal Therapeutic Phage Preparations
Our Published Output
Conclusions: Polish Phage Therapy
Acknowledgments: Polish Phage Therapy
Current Status of Russian Research
Background
Russian Phage Therapy Research and Implementation
Conclusions: Russian Phage Therapy
References
The Use of Bacteriophages in Veterinary Therapy
Introduction
History of Bacteriophages in Veterinary Use
Systemic Escherichia coli Infections
Systemic Salmonella Infections
Intestinal E. coli Infections
Intestinal Salmonella Infections
Intestinal Campylobacter Infections
Other Systemic Infections
Other Infections
Use in the Food Production Chain
Applications, Potential, and Problems
Regulatory Approval
Cross-References
References
Enzybiotics: Endolysins and Bacteriocins
Endolysins, the Model Enzybiotic
Lysis from Without
Endolysin Structure
Bacteriolytic Mechanism
Antimicrobial Development of Endolysins
Specificity and Resistance
Toxicity
Immunogenicity
Synergy
Endolysin Applications
Medicine
Food Safety
Agriculture
Endolysin Engineering Approaches
Chimeragenesis
Directed Evolution
Structure-Guided Site-Directed Mutagenesis
Gram-Negative Engineering Approaches
Targeting Intracellular Pathogens
Regulatory Aspects of Endolysins
Other Phage-Based Enzybiotics
Particulate Bacteriocins
Applications in Crop Health
Applications in Medicine
Engineering Particulate Bacteriocins
Concluding Remarks
Cross-References
References
Phage Display Technology and the Development of Phage-Based Vaccines
Phage Display Technology
Introduction
Combinatorial Chemistry and Display Phage Technology
Combinatorial Chemistry
Phage Display Technology
Display Phage
Affinity Selection
Amplification Bias
Subtractive Panning
Biopanning Apparatus
Characterization of Selected Ligands
Phage Capture Assay
Western Blot Analysis
Inhibition ELISA
DNA Sequence Analysis
Conclusion
Phage as Delivery Vehicles
Introduction
Preparation of Modified Phages
Modification of Coat Proteins
Modification and Addition of Nonstructural Genes
Synthetic Phages
Applications of Modified Phages
Phages as Vaccine Delivery Vehicles
Phage-Mediated Protein Vaccines
Phage DNA Vaccines
Phages as Gene Therapy Vectors
Conclusion
Development of Monoclonal Antibody Mimics
Introduction
Small Peptide Mimics of mAbs
Mimotopes
Selection of mAb Mimics (Anti-epitopic Peptides)
Peptide-Based Cytotoxicity
Conclusion
References
Phage Therapy Collaboration and Compassionate Use
Introduction
Regulation of Compassionate Phage Therapy
General Process of Compassionate Phage Therapy
Establishing Medical Need and Complying with Regulations
Identifying Sources of Phages
Phage Susceptibility Testing
Preparing Phages for the Patient
Administering Phages to the Patient
Coordinating Compassionate Phage Therapy
Costs of Compassionate Phage Therapy
Recent Examples of Compassionate Phage Therapy
Diabetic Toe Ulcers (US/Georgia Collaboration)
Disseminated Acinetobacter Infection (US Collaboration)
Posttransplant Burkholderia Infection (US/Canada Collaboration)
Other US Cases
Polymicrobial Bone Infection (Israel/US Collaboration)
Engineered Phage Therapy (UK/US Collaboration)
Global Crowdsourcing of Klebsiella Phages (Finland/US/Israel/UK/Switzerland Collaboration)
New Systems Created to Facilitate Compassionate Phage Therapy
Phage Therapy at the Queen Astrid Military Hospital
Phage Directory
Center for Innovative Phage Applications and Therapeutics (IPATH)
Vitalis Phage Therapy
Summary and Concluding Remarks
Cross-References
References
Clinical Trials of Bacteriophage Therapeutics
Introduction
From Antibiotics to Phage
From East to West
Modern Phage Trials to Date
P. areuginosa Chronic Otitis Externa
Chronic Venous Leg Ulcers
Immunoresponse in HIV Patients
E. coli Pediatric Diarrhea: The Bangladesh Trials
Burn Wound Infections
S. aureus Diabetic Toe Ulcers
S. aureus Chronic Rhinosinusitis
Case Reports
Phage Therapy Unit, Wroclaw, Poland
PhagoBioDerm
The Eliava Institute and Medical Tourism
Hurdles to the Development of Phage Therapy in the Western World
Regulatory Framework
Finances
Resistance
Biological Considerations
Recommendations
Conclusion
Cross-References
References
Selection of Disease Targets for Phage Therapy
Introduction
Current Position
Issues in the Selection of the Target Disease
Bacterial Nature of the Underlying Disease
Unmet Need
Limited Range of Bacterial Targets
Bacteria Causing the Disease Are Identified
Bacteria Targeted Are Responsible for the Observed Pathology
Availability of Model Systems for Preclinical Work
Practicality of Clinical Trials
Accessibility of the Bacterial Target
The Effect of Bacterial Numbers
Issues in the Selection of Bacteriophages
Availability of Bacteriophages
Suitability of Bacteriophages for Therapeutic Use
Lysogeny
Transduction and Toxin Carriage
Host Range
Other Issues with Bacteriophage Mixtures
Storage and Stability
Commercial Considerations
Suitability of Product
Considerations on the Nature of Bacteriophages
Summary
Glossary
References
Regulatory Considerations for Bacteriophage Therapy Products: USA
Background
Regulatory Oversight of Biological Products
Chemistry, Manufacturing, and Controls for Bacteriophage Products
Expanded Access to Investigational Drugs for Treatment Use
Defined Bacteriophage Products Versus Bacteriophage Banks
Conclusions
References
Regulatory Aspects of the Therapeutic Use of Bacteriophages: Europe
Background
Regulatory Oversight and Development Guidance
Regulatory Framework
Development Guidance
Quality Parameters
Non-clinical and Clinical Development
Phage Therapy Modalities and Ongoing Research Activities
Access Issues
Conclusion
References
Index