Antimicrobial Peptides (Advances in Molecular and Cellular Biology Series)

249 Pages·2010·3.18 MB·English

by  Guangshun Wang

Advances in Molecular and Cellular Microbiology 18
Antimicrobial Peptides
Discovery, Design and Novel Therapeutic
Strategies
Edited by
Guangshun Wang, PhD
Eppley Institute
University of Nebraska Medical Center
Omaha, Nebraska, USA
Advances in Molecular and
Cellular Microbiology
Through the application of molecular and cellular microbiology we now recognize the
diversity and dominance of microbial life forms that exist in all environments on our
planet. These microbes have many important planetary roles, but for humans a major
problem is their ability to colonize our tissues and cause disease. The same techniques
of molecular and cellular microbiology have been applied to the problems of human
and animal infection since the 1990s and have proved to be immensely powerful tools
in elucidating how microorganisms cause human pathology. This series has the aim of
providing information on the advances that have been made in the application of
molecular and cellular microbiology to specifi c organisms and the diseases they cause.
The series is edited by researchers active in the application of molecular and cellular
microbiology to human disease states. Each volume focuses on a particular aspect of
infectious disease and will enable graduate students and researchers to keep up with
the rapidly diversifying literature in current microbiological research.
Series Editors
Professor Brian Henderson
University College London
Professor Michael Wilson
University College London
Titles Available from CABI
17. Helicobacter pylori in the 21st Century
Edited by Philip Sutt on and Hazel M. Mitchell
18. Antimicrobial Peptides: Discovery, Design and Novel Therapeutic Strategies
Edited by Guangshun Wang
Titles Forthcoming from CABI
Stress Response in Pathogenic Bacteria
Edited by Stephen Kidd
Lyme Disease: an Evidence-based Approach
Edited by John Halperin
Tuberculosis: Molecular Techniques in Diagnosis and Treatment
Edited by Timothy McHugh
Microbial Metabolomics
Edited by Silas Villas-Bôas and Katya Ruggiero
Earlier titles in the series are available from Cambridge University Press (www.cup.cam.ac.uk).
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Library of Congress Cataloging-in-Publication Data
Antimicrobial peptides : discovery, design, and novel therapeutic
strategies / edited by Guangshun Wang.
p. ; cm. -- (Advances in molecular and cellular microbiology ; 18)
Includes bibliographical references and index.
ISBN 978-1-84593-657-0 (alk. paper)
1. Peptide antibiotics. I. Wang, Guangshun. II. Series: Advances in molecular and
cellular microbiology ; 18.
[DNLM: 1. Antimicrobial Cationic Peptides. 2. Anti-Infective Agents. 3. Drug
Design. 4. Immunity, Innate. QU 68 A6308 2010]
RS431.P37A575 2010
615’.1--dc22
2010016796
ISBN-13: 978 1 84593 657 0
Commissioning editor: Rachel Cutt s
Production editor: Tracy Head
Typeset by Columns Design Ltd, Reading, UK.
Printed and bound in the UK by CPI Antony Rowe, Chippenham.
Contents
Contributors xi
Preface xiii
Introduction xv
Michael Zasloff
Part I: Natural Antimicrobial Peptides: Nomenclature, Classification and
Interesting Templates for Peptide Engineering
1 A Database View of Naturally Occurring Antimicrobial Peptides:
Nomenclature, Classifi cation and Amino Acid Sequence Analysis 1
Guangshun Wang, Xia Li and Michael Zasloff
1.1 Database Scope and Overview 2
1.2 Nomenclature of Antimicrobial Peptides 3
1.2.1 Peptide-based method 4
1.2.2 Source-based method 4
1.2.3 Source and peptide combined method 4
1.3 Annotation and Classifi cation of Antimicrobial Peptides 5
1.3.1 Source organisms and peptide family classifi cation 5
1.3.2 Classifi cation based on biological activities 8
1.3.3 Classifi cation based on peptide characteristics 9
1.3.4 Peptide-binding targets and mechanisms of action 14
1.4 Amino Acid Sequence Analysis of Antimicrobial Peptides 15
1.5 Concluding Remarks 17
2 Lantibiotic-related Research and the Application Thereof 22
Brian Healy, Jim O’Mahony, Colin Hill, Paul D. Cott er and R. Paul Ross
2.1 Introduction to Bacteriocins 22
2.2 Biosynthesis and Post-translational Modifi cations 23
2.3 Classifi cation 24
2.4 Lantibiotic Subgroups: Biology, Structure and Mode of Action 25
2.4.1 Nisin-like lantibiotics 25
2.4.2 Epidermin-like lantibiotics 26
v
vi Contents
2.4.3 Planosporicin- and streptin-like lantibiotics 27
2.4.4 Pep5-like peptides 27
2.4.5 Lacticin 481-like lantibiotics 27
2.4.6 Mersacidin-like lantibiotics 28
2.4.7 LtnA2-like peptides 28
2.4.8 Other type II lantibiotics 28
2.5 Current and Future Use of Lantibiotics for Food Applications 29
2.6 Lantibiotics and Their Medical Applications 30
2.7 Engineering of Lantibiotics 30
2.8 Screening for New Lantibiotics 31
2.9 Concluding Remarks and Perspectives 32
3 Antimicrobial Peptides in Plants 40
Quentin Kaas, Jan-Christoph Westermann, Sónia Troeira Henriques and David J. Craik
3.1 Introduction to Plant Antimicrobial Peptides 40
3.1.1 Lipid-transfer proteins 41
3.1.2 Thionins 43
3.1.3 Plant defensins 44
3.1.4 Chitin-binding peptides 45
3.1.5 Miscellaneous AMPs from plants 48
3.1.6 Non-ribosomal antimicrobial peptides 49
3.2 Cyclotides 49
3.2.1 Diversity of plant cyclotides 49
3.2.2 Detection and isolation of cyclotides 54
3.2.3 Cyclotide biosynthesis 54
3.2.4 Biological activities of cyclotides 56
3.2.5 Cyclotide engineering and mass production 62
3.3 Concluding Remarks and Perspectives 63
Part II: Expanding the Peptide Space: Prediction Methods, Design Strategies and
Peptidomimetics
4 Database-aided Prediction and Design of Novel Antimicrobial Peptides 72
Guangshun Wang
4.1 Database-aided Antimicrobial Peptide Prediction 73
4.1.1 Prediction based on mature peptides 73
4.1.2 Prediction based on highly conserved propeptide sequences 75
4.1.3 Prediction based on both propeptides and mature peptides 75
4.1.4 Prediction based on processing enzymes 76
4.1.5 Genomic context-based bacteriocin prediction 76
4.2 Database-aided Peptide Design and Improvement 76
4.2.1 Database screening for HIV inhibitory antimicrobial peptides 76
4.2.2 Sequence shuffl ing is a primitive combinatorial approach 77
4.2.3 The hybrid approach and grammar-based peptide design 78
4.2.4 De novo peptide design 78
4.2.5 Database-aided enhancement of peptide anti-HIV activity 80
4.3 Strategies for Improving Cell Selectivity of AMPs 80
4.4 Strategies for Improving Peptide Stability to Proteases 82
4.5 Concluding Remarks 82
Contents vii
5 Discovery of Novel Antimicrobial Peptides Using Combinatorial Chemistry
and High-throughput Screening 87
William C. Wimley
5.1 The Interfacial Activity Model of AMP Activity 87
5.2 Combinatorial Chemistry Methods 88
5.2.1 Overview of library synthesis 88
5.2.2 Non-indexed methods 89
5.2.3 Indexed methods 90
5.3 High-throughput Screening 90
5.3.1 Biological assays 90
5.3.2 Selection of broad-spectrum peptide antibiotics 92
5.3.3 Non-biological assays 94
5.4 Accomplishments 97
5.4.1 Beyond high-throughput screening 97
5.5 Future Directions 98
6 Chemical Mimics with Systemic Effi cacy 100
Amram Mor
6.1 Introduction 100
6.2 De Novo-designed Rigid Peptidomimetics 102
6.2.1 Hairpin-shaped peptides 102
6.2.2 Peptoids 103
6.2.3 Arylamides 103
6.3 Acyl-lysyl Oligomers 104
6.3.1 Design 104
6.3.2 Structure–activity relationships 104
6.3.3 Antibacterial properties 107
6.3.4 Antiparasital properties 109
6.4 Concluding Remarks and Perspectives 110
Part III: Biophysics, Structural Biology and Mechanism of Action of
Antimicrobial Peptides
7 Biophysical Analysis of Membrane-targeting Antimicrobial Peptides:
Membrane Properties and the Design of Peptides Specifi cally Targeting
Gram-negative Bacteria 116
Richard M. Epand and Raquel F. Epand
7.1 Diff erences in Chemical Composition and Molecular Organization of
Gram-positive and Gram-negative Bacteria 116
7.2 Role of Bacterial Membrane Lipid Composition in Antimicrobial Sensitivity 118
7.3 Antimicrobial Agents that Target the Outer Membrane of Gram-negative
Bacteria 119
7.4 Antimicrobial Agents that Promote Clustering of Anionic Lipids 120
7.4.1 Evidence for lipid clustering 120
7.4.2 Bacterial species specifi city of toxicity 121
7.4.3 Putative mechanism of action 124
7.4.4 Properties of antimicrobial agents that favour clustering 125
7.4.5 Sources of energy to account for clustering and entropy of demixing 125
7.5 Concluding Remarks and Perspectives 125
vviiiiii CCoonntteennttss
8 Non-membrane Targets of Antimicrobial Peptides: Novel Therapeutic
Opportunities? 128
Ju Hyun Cho and Sun Chang Kim
8.1 Introduction 128
8.2 Buforin II: α-Helical AMP with Single Proline Residue Binding to Nucleic Acids 130
8.3 PR-39 and Indolicidin: Mammalian Proline-rich Peptides Inhibiting
Macromolecule Synthesis and Cell Division 131
8.4 Apidaecin, Drosocin and Pyrrhocoricin: Short, Insect Proline-rich Peptides
Binding to Heat-shock Protein DnaK 133
8.5 Concluding Remarks and Perspectives 136
9 Structural Studies of Antimicrobial Peptides Provide Insight into Their
Mechanisms of Action 141
Guangshun Wang
9.1 Human Defensins and Cathelicidins 141
9.2 Bacterial Expression and Purifi cation of Antimicrobial Peptides 143
9.3 Structural Studies of Membrane-targeting Antimicrobial Peptides 146
9.3.1 Membrane-mimetic models 146
9.3.2 NMR methods 147
9.3.3 Three-dimensional structures of antimicrobial peptides 149
9.3.4 Interactions of antimicrobial peptides with bacterial membranes by
NMR spectroscopy 155
9.3.5 Structural basis of peptide selectivity 159
9.4 Structure-based Peptide Engineering 159
9.5 Concluding Remarks and Perspectives 160
Part IV: Novel Therapeutic Strategies to Bolster Host Defence
10 Lung Infection: Shift ing the Equilibrium Towards the Free and Active Form
of Human LL-37 and the Design of Alternative Antimicrobial Agents 169
Paul A. Janmey and Robert Bucki
10.1 Introduction 169
10.1.1 Electrostatic properties of LL-37 169
10.1.2 Interaction of polyvalent cations with linear polyelectrolytes 170
10.2 Production of Anionic Polyelectrolytes by Host and Microbial Sources 171
10.3 Sequestration and Inactivation of LL-37 by DNA and F-actin 172
10.4 Releasing LL-37 from Polyelectrolyte Bundles 172
10.4.1 Severing polymers with DNase, gelsolin and alginase 173
10.4.2 Destabilizing bundles with small multivalent anions 174
10.5 Designing Antimicrobial Agents Resistant to Inactivation by Polyelectrolytes 174
10.5.1 Cationic steroids: minimizing and redistributing charge 175
10.5.2 Increasing the hydrophobicity of antimicrobial agents 175
10.6 Possible Therapeutic Use 175
10.6.1 Selective use in some body fl uids and not others 175
10.6.2 Stimulation of host cells 176
10.7 Conclusion 176
Contents ix
11 Role of Vitamin D in the Enhancement of Antimicrobial Peptide Gene
Expression 181
John H. White and Ari J. Bitt on
11.1 Vitamin D 181
11.2 Early History of Vitamin D 181
11.3 Vitamin D Defi ciency 182
11.4 Vitamin D Signalling and Mechanisms of Action 182
11.5 Overview of Vitamin D and Immune System Regulation 184
11.6 Vitamin D as a Regulator of Antimicrobial Peptide Gene Expression 185
11.7 Antimicrobial Peptides 185
11.8 Regulation of DEFB2/hBD-2 Expression by 1,25D 186
11.9 1,25D Regulation of LL-37 is Human and Primate Specifi c 187
11.10 Broader Physiological and Pathophysiological Implications of the Regulation
of LL-37 Expression by 1,25D 188
11.11 Therapeutic Role for Vitamin D Analogues 190
12 Fine Tuning Host Responses in the Face of Infection: Emerging Roles and Clinical
Applications of Host Defence Peptides 195
Matt hew L. Mayer, Donna M. Easton and Robert E.W. Hancock
12.1 Mammalian Host Defence (Antimicrobial) Peptides 196
12.1.1 Defensins 196
12.1.2 Cathelicidins 197
12.2 The Role of Endogenous Host Defence Peptides in the Response to Infection 198
12.2.1 Natriuretic peptides 201
12.3 Potential Therapeutic Uses beyond Anti-infective Activity 202
12.3.1 Adjuvant potential 204
12.3.2 Wound-healing activity 205
12.4 Recent Clinical Advances in Therapeutic Application of Host Defence
Peptides 206
12.5 Innate Defence Regulators as Anti-infective Therapeutics 208
12.6 Rational Design of Immunomodulatory Peptides 209
12.7 Limitations and Challenges 209
12.8 Conclusions 211
Index 221