Cover

Half Title

Title

Copyright

Contents

Contributors

Preface

Introduction to the Second Edition

PART I: OVERVIEW OF ANTIMICROBIAL PEPTIDES

1 Discovery, Classification and Functional Diversity of Antimicrobial Peptides

1.1 A Brief Timeline of Discovery

1.2 Nomenclature of Antimicrobial Peptides

1.3 Classification of Antimicrobial Peptides

1.4 Functional Diversity and Terminology of Antimicrobial Peptides

1.5 Concluding Remarks

PART II: NATURAL TEMPLATES FOR PEPTIDE ENGINEERING

2 Structural and Functional Diversity of Cathelicidins

2.1 Introduction

2.2 Discovery of Cathelicidins

2.3 Evolution, Structural Diversity and Features of the Proregion

2.4 Expression and Processing

2.5 Structure-dependent Mode of Action

2.6 Pleiotropic Roles of Cathelicidins in Host Defence and Potential Applications

2.7 Conclusions

3 Disulfide-linked Defensins

3.1 Overview

3.2 Vertebrate Defensins

3.3 Arthropod Defensins

3.4 Plant Defensins

3.5 When is a Disulfide-linked Antimicrobial Peptide not a Defensin?

3.6 Therapeutic Potential of Synthetic Disulfide-linked Defensin Peptides

3.7 Summary

4 Lantibiotics: Bioengineering and Applications

4.1 Lantibiotics: Background, Structure, Mode of Action and Classification

4.2 Lantibiotics as Clinical and Chemotherapeutic Agents

4.3 Lantibiotics as Biopreservatives

4.4 Lantibiotic Bioengineering and Synthetic Engineering

4.5 Future Outlook and Conclusion

PART III: EXPANDING PEPTIDE SPACE : COMBINATORIAL LIBRARY , GENOME -BASED PREDICTION AND DE NOVO DESIGN

5 Discovery of Novel Antimicrobial Peptides Using Combinatorial Chemistry and High-throughput Screening

5.1 The Interfacial Activity Model of AMP Activity

5.2 Combinatorial Chemistry Methods

5.3 High-throughput Screening

5.4 Accomplishments

5.5 Future Directions

6 Prediction and Design of Antimicrobial Peptides: Methods and Applications to Genomes and Proteomes

6.1 Antimicrobial Peptide Prediction

6.2 Database-aided Peptide Design and Improvement

6.3 Computational Design of Novel AMPs

6.4 Prediction Based on Biophysical Approaches

6.5 Concluding Remarks

PART IV: MECHANISMS OF ACTION: BIOPHYSICS AND STRUCTURAL BIOLOGY

7 Antimicrobial Peptides: Multiple Mechanisms against a Variety of Targets

7.1 Target Selectivity of Antimicrobial Peptides

7.2 Membrane-lytic Antimicrobial Peptides

7.3 Intracellular Targets of Antimicrobial Peptides

7.4 LPS and LTA Neutralization by Antimicrobial Peptides

7.5 Antibiofilm Antimicrobial Peptides

7.6 Antifungal Antimicrobial Peptides

7.7 Anticancer Antimicrobial Peptides

7.8 Antiviral Antimicrobial Peptides

7.9 Antimicrobial Peptide Modification and How It Affects the Mode of Action

7.10 Conclusion

8 Microbial Membranes and the Action of Antimicrobial Peptides

8.1 Introduction

8.2 Physicochemical Properties of AMPs and the Molecular Organization of The Cell Envelope of Different Microorganisms

8.3 The Role of Cell Wall Components on AMP Toxicity

8.4 Membrane Lipid Composition and AMP Sensitivity

8.5 Antimicrobial Agents that Promote Clustering of Anionic Lipids

8.6 Synergistic Action of AMPs and Other Antimicrobial Agents

8.7 Summary and Future Perspective

9 Non-membranolytic Mechanisms of Action of Antimicrobial Peptides – Novel Therapeutic Opportunities?

9.1 Introduction

9.2 Intracellular Mode of Action

9.3 Cell Surface Modes of Action

9.4 Other Membrane-independent Mechanisms of Bacterial Killing

9.5 Immune Modulatory Effects

9.6 Towards Novel Therapeutic Opportunities

9.7 Concluding Remarks

10 Structural Insight into the Mechanisms of Action of Antimicrobial Peptides and Structure-based Design

10.1 Introduction to Structural Methods and Membrane Models

10.2 Three-dimensional Structures of Antimicrobial Peptides

10.3 Structure-based Peptide Design

10.4 Concluding Remarks

PART V: NOVEL THERAPEUTIC STRATEGIES: SYNERGY, IMMUNE MODULATION, SURFACE COATING AND DELIVERY

11 Synergy of Antimicrobial Peptides

11.1 Introduction

11.2 Principles of Synergy of Antimicrobial Peptides

11.3 How Antimicrobial Peptides Synergize to Kill Microorganisms

11.4 Synergism of Antimicrobial Peptides with Conventional Antibiotics

11.5 Synergy with AMP Analogues

11.6 Conclusion

12 Surface Immobilization of Antimicrobial Peptides to Prevent Biofilm Formation

12.1 Introduction

12.2 Surface Coating Methods

12.3 Chemical and Physical Characterization of Peptide Coated Surfaces

12.4 Antimicrobial and Antibiofilm Activities of Peptide Coated Surfaces

12.5 Mechanism of Action of Immobilized Peptides

12.6 Biocompatibility

12.7 Conclusions and Future Outlook

13 Sustained Delivery of Cathelicidin Antimicrobial Peptide-inducing Compounds to Minimize Infection and Enhance Wound Healing

13.1 Introduction

13.2 The Role of the CAMP Gene in Protection against Infection

13.3 LL-37 Modulates the Host Immune Response

13.4 Function of Vitamin D Signalling in Normal Skin Homeostasis

13.5 The Role of Vitamin D and CAMP/LL-37 in Cutaneous Wound Healing

13.6 Induction of CAMP Gene Expression by Other Natural Compounds

13.7 Preventing Infections and Improving Wound Healing with Vitamin D 3 and Other Immune Boosting Compounds

13.8 Summary

14 Immunomodulatory Activities of Cationic Host Defence Peptides and Novel Therapeutic Strategies

14.1 Classical AMPs and HDPs

14.2 Hormones and Neuropeptides: The New HDPs

14.3 Activities of HDPs

14.4 HDPs as Therapeutics: Peptides in Clinical Trials

14.5 Conclusions

Index