Moonlighting proteins : novel virulence factors in bacterial infections

468 Pages·2017·7.984 MB·English

by  Brian Henderson

Moonlighting Proteins
Moonlighting Proteins: Novel Virulence
Factors in Bacterial Infections
Edited by Brian Henderson
Division of Infection and Immunity, University College London, London, UK
Copyright © 2017 by John Wiley & Sons, Inc. All rights reserved
Published by John Wiley & Sons, Inc., Hoboken, New Jersey
Published simultaneously in Canada
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Library of Congress Cataloging‐in‐Publication Data
Names: Henderson, Brian (Professor) editor.
Title: Moonlighting proteins : novel virulence factors in bacterial infections /
Edited by Brian Henderson.
Description: Hoboken, New Jersey : John Wiley & Sons, Inc., [2017] | Includes bibliographical
references and index.
Identifiers: LCCN 2016049475 (print) | LCCN 2016051302 (ebook) | ISBN 9781118951118 (cloth) |
ISBN 9781118951125 (pdf) | ISBN 9781118951132 (epub)
Subjects: | MESH: Bacterial Proteins–physiology | Virulence Factors | Bacterial Infections
Classification: LCC RA644.B32 (print) | LCC RA644.B32 (ebook) | NLM QW 52 | DDC 614.5/7–dc23
LC record available at https://lccn.loc.gov/2016049475
Cover Image: © SEBASTIAN KAULITZKI/SCIENCE PHOTO LIBRARY/Getty Images
Cover Design: Wiley
Set in 10/12pt Warnock by SPi Global, Pondicherry, India
10 9 8 7 6 5 4 3 2 1
v
Contents
List of Contributors xv
Preface xix
About the Editor xxiii
Part I Overview of Protein Moonlighting 1
1 What is Protein Moonlighting and Why is it Important? 3
Constance J. Jeffery
1.1 What is Protein Moonlighting? 3
1.2 Why is Moonlighting Important? 5
1.2.1 Many More Proteins Might Moonlight 5
1.2.2 Protein Structure/Evolution 5
1.2.3 Roles in Health and Disease 8
1.2.3.1 Humans 8
1.2.3.2 Bacteria 10
1.3 Current questions 11
1.3.1 How Many More Proteins Moonlight? 11
1.3.2 How Can We Identify Additional Proteins That Moonlight and all
the Moonlighting Functions of Proteins? 11
1.3.3 In Developing Novel Therapeutics, How Can We Target the
Appropriate Function of a Moonlighting Protein and Not Affect Other
Functions of the Protein? 12
1.3.4 How do Moonlighting Proteins get Targeted to More Than One
Location in the Cell? 12
1.3.5 What Changes in Expression Patterns Have Occurred to Enable
the Protein to be Available in a New Time and Place to Perform a
New Function? 12
1.4 Conclusions 13
References 13
2 Exploring Structure–Function Relationships in Moonlighting
Proteins 21
Sayoni Das, Ishita Khan, Daisuke Kihara, and Christine Orengo
2.1 Introduction 21
2.2 Multiple Facets of Protein Function 22
vi Contents
2.3 The Protein Structure–Function Paradigm 23
2.4 Computational Approaches for Identifying Moonlighting
Proteins 25
2.5 Classification of Moonlighting Proteins 26
2.5.1 Proteins with Distinct Sites for Different Functions in the Same
Domain 27
2.5.1.1 α‐Enolase, Streptococcus pneumonia 27
2.5.1.2 Albaflavenone monooxygenase, Streptomyces coelicolor A3(2) 29
2.5.1.3 MAPK1/ERK2, Homo sapiens 30
2.5.2 Proteins with Distinct Sites for Different Functions in More Than One
Domain 30
2.5.2.1 Malate synthase, Mycobacterium tuberculosis 31
2.5.2.2 BirA, Escherichia coli 31
2.5.2.3 MRDI, Homo sapiens 33
2.5.3 Proteins Using the Same Residues for Different Functions 33
2.5.3.1 GAPDH E. coli 33
2.5.3.2 Leukotriene A4 hydrolase, Homo sapiens 33
2.5.4 Proteins Using Different Residues in the Same/Overlapping Site
for Different Functions 34
2.5.4.1 Phosphoglucose isomerase, Oryctolagus cuniculus, Mus musculus,
Homo sapiens 34
2.5.4.2 Aldolase, Plasmodium falciparum 36
2.5.5 Proteins with Different Structural Conformations for Different
Functions 36
2.5.5.1 RfaH, E. coli 36
2.6 Conclusions 37
References 39
Part II Proteins Moonlighting in Prokarya 45
3 Overview of Protein Moonlighting in Bacterial Virulence 47
Brian Henderson
3.1 Introduction 47
3.2 The Meaning of Bacterial Virulence and Virulence Factors 47
3.3 Affinity as a Measure of the Biological Importance of Proteins 49
3.4 Moonlighting Bacterial Virulence Proteins 50
3.4.1 Bacterial Proteins Moonlighting as Adhesins 52
3.4.2 Bacterial Moonlighting Proteins That Act as Invasins 59
3.4.3 Bacterial Moonlighting Proteins Involved in Nutrient Acquisition 59
3.4.4 Bacterial Moonlighting Proteins Functioning as Evasins 60
3.4.5 Bacterial Moonlighting Proteins with Toxin‐like Actions 63
3.5 Bacterial Moonlighting Proteins Conclusively Shown to be Virulence
Factors 64
3.6 Eukaryotic Moonlighting Proteins That Aid in Bacterial Virulence 66
3.7 Conclusions 67
References 68
Contents vii
4 Moonlighting Proteins as Cross‐Reactive Auto‐Antigens 81
Willem van Eden
4.1 Autoimmunity and Conservation 81
4.2 Immunogenicity of Conserved Proteins 82
4.3 HSP Co‐induction, Food, Microbiota, and T-cell Regulation 84
4.3.1 HSP as Targets for T‐Cell Regulation 85
4.4 The Contribution of Moonlighting Virulence Factors
to Immunological Tolerance 87
References 88
Part III Proteins Moonlighting in Bacterial Virulence 93
Part 3.1 Chaperonins: A Family of Proteins with Widespread
Virulence Properties 95
5 Chaperonin 60 Paralogs in Mycobacterium tuberculosis and Tubercle
Formation 97
Brian Henderson
5.1 Introduction 97
5.2 Tuberculosis and the Tuberculoid Granuloma 97
5.3 Mycobacterial Factors Responsible for Granuloma Formation 98
5.4 Mycobacterium tuberculosis Chaperonin 60 Proteins, Macrophage
Function, and Granuloma Formation 100
5.4.1 Mycobacterium tuberculosis has Two Chaperonin 60 Proteins 100
5.4.2 Moonlighting Actions of Mycobacterial Chaperonin 60 Proteins 101
5.4.3 Actions of Mycobacterial Chaperonin 60 Proteins Compatible
with the Pathology of Tuberculosis 102
5.4.4 Identification of the Myeloid‐Cell‐Activating Site in M. tuberculosis
Chaperonin 60.1 105
5.5 Conclusions 106
References 106
6 Legionella pneumophila Chaperonin 60, an Extra‐ and Intra‐Cellular
Moonlighting Virulence‐Related Factor 111
Karla N. Valenzuela‐Valderas, Angela L. Riveroll, Peter Robertson,
Lois E. Murray, and Rafael A. Garduño
6.1 Background 111
6.2 HtpB is an Essential Chaperonin with Protein‐folding Activity 112
6.3 Experimental Approaches to Elucidate the Functional Mechanisms
of HtpB 112
6.3.1 The Intracellular Signaling Mechanism of HtpB in Yeast 113
6.3.2 Yeast Two‐Hybrid Screens 118
6.4 Secretion Mechanisms Potentially Responsible for Transporting HtpB
to Extracytoplasmic Locations 120
6.4.1 Ability of GroEL and HtpB to Associate with Membranes 121
6.4.2 Ongoing Mechanistic Investigations on Chaperonins Secretion 122
viii Contents
6.5 Identifying Functionally Important Amino Acid Positions
in HtpB 124
6.5.1 Site‐Directed Mutagenesis 125
6.6 Functional Evolution of HtpB 126
6.7 Concluding Remarks 127
References 129
Part 3.2 Peptidylprolyl Isomerases, Bacterial Virulence,
and Targets for Therapy 135
7 An Overview of Peptidylprolyl Isomerases (PPIs) in Bacterial
Virulence 137
Brian Henderson
7.1 Introduction 137
7.2 Proline and PPIs 137
7.3 Host PPIs and Responses to Bacteria and Bacterial Toxins 138
7.4 Bacterial PPIs as Virulence Factors 138
7.4.1 Proposed Mechanism of Virulence of Legionella pneumophila
Mip 140
7.5 Other Bacterial PPIs Involved in Virulence 140
7.6 Conclusions 142
References 142
Part 3.3 Glyceraldehyde 3‐Phosphate Dehydrogenase (GAPDH):
A Multifunctional Virulence Factor 147
8 GAPDH: A Multifunctional Moonlighting Protein in Eukaryotes
and Prokaryotes 149
Michael A. Sirover
8.1 Introduction 149
8.2 GAPDH Membrane Function and Bacterial Virulence 150
8.2.1 Bacterial GAPDH Virulence 151
8.2.2 GAPDH and Iron Metabolism in Bacterial Virulence 153
8.3 Role of Nitric Oxide in GAPDH Bacterial Virulence 153
8.3.1 Nitric Oxide in Bacterial Virulence: Evasion
of the Immune Response 154
8.3.2 Formation of GAPDHcys‐NO by Bacterial NO Synthases 155
8.3.3 GAPDHcys‐NO in Bacterial Virulence: Induction
of Macrophage Apoptosis 155
8.3.4 GAPDHcys‐NO in Bacterial Virulence: Inhibition
of Macrophage iNOS Activity 156
8.3.5 GAPDHcys‐NO in Bacterial Virulence: Transnitrosylation
to Acceptor Proteins 157
8.4 GAPDH Control of Gene Expression
and Bacterial Virulence 158
8.4.1 Bacterial GAPDH Virulence 159
Contents ix
8.5 Discussion 160
Acknowledgements 162
References 162
9 Streptococcus pyogenes GAPDH: A Cell‐Surface Major Virulence
Determinant 169
Vijay Pancholi
9.1 Introduction and Early Discovery 169
9.2 GAS GAPDH: A Major Surface Protein with Multiple Binding
Activities 170
9.3 AutoADP‐Ribosylation of SDH and Other
Post‐Translational Modifications 172
9.4 Implications of the Binding of SDH to Mammalian Proteins for Cell
Signaling and Virulence Mechanisms 173
9.5 Surface Export of SDH/GAPDH: A Cause or Effect? 178
9.6 SDH: The GAS Virulence Factor‐Regulating Virulence Factor 180
9.7 Concluding Remarks and Future Perspectives 183
References 183
10 Group B Streptococcus GAPDH and Immune Evasion 195
Paula Ferreira and Patrick Trieu‐Cuot
10.1 The Bacterium GBS 195
10.2 Neonates are More Susceptible
to GBS Infection than Adults 195
10.3 IL‐10 Production Facilitates Bacterial Infection 196
10.4 GBS Glyceraldehyde‐3‐Phosphate Dehydrogenase Induces IL‐10
Production 197
10.5 Summary 199
References 200
11 Mycobacterium tuberculosis Cell‐Surface GAPDH Functions
as a Transferrin Receptor 205
Vishant M. Boradia, Manoj Raje, and Chaaya Iyengar Raje
11.1 Introduction 205
11.2 Iron Acquisition by Bacteria 206
11.2.1 Heme Uptake 206
11.2.2 Siderophore‐Mediated Uptake 207
11.2.3 Transferrin Iron Acquisition 207
11.3 Iron Acquisition by Intracellular Pathogens 207
11.4 Iron Acquisition by M. tb 208
11.4.1 Heme Uptake 208
11.4.2 Siderophore‐Mediated Iron Acquisition 209
11.4.3 Transferrin‐Mediated Iron Acquisition 209
11.5 Glyceraldehyde‐3‐Phosphate Dehydrogenase (GAPDH) 210
11.6 Macrophage GAPDH and Iron Uptake 210
11.6.1 Regulation 210
11.6.2 Mechanism of Iron Uptake and Efflux 211
11.6.3 Role of Post‐Translational Modifications 211
x Contents
11.7 Mycobacterial GAPDH and Iron Uptake 212
11.7.1 Regulation 212
11.7.2 Mechanism of Iron Uptake 215
11.7.3 Uptake by Intraphagosomal M. tb 216
11.8 Conclusions and Future Perspectives 216
Acknowledgements 218
References 219
12 GAPDH and Probiotic Organisms 225
Hideki Kinoshita
12.1 Introduction 225
12.2 Probiotics and Safety 225
12.3 Potential Risk of Probiotics 227
12.4 Plasminogen Binding and Enhancement
of its Activation 228
12.5 GAPDH as an Adhesin 229
12.6 Binding Regions 232
12.7 Mechanisms of Secretion and Surface Localization 234
12.8 Other Functions 235
12.9 Conclusion 236
References 237
Part 3.4 Cell‐Surface Enolase: A Complex Virulence Factor 245
13 Impact of Streptococcal Enolase in Virulence 247
Marcus Fulde and Simone Bergmann
13.1 Introduction 247
13.2 General Characteristics 248
13.3 Expression and Surface Exposition of Enolase 249
13.4 Streptococcal Enolase as Adhesion Cofactor 252
13.4.1 Enolase as Plasminogen‐Binding Protein 252
13.4.1.1 Plasminogen‐Binding Sites of Streptococcal Enolases 253
13.4.2 Role of Enolase in Plasminogen‐Mediated Bacterial‐Host Cell
Adhesion and Internalization 254
13.4.3 Enolase as Plasminogen‐Binding Protein
in Non‐Pathogenic Bacteria 255
13.5 Enolase as Pro‐Fibrinolytic Cofactor 256
13.5.1 Degradation of Fibrin Thrombi and Components of the Extracellular
Matrix 257
13.6 Streptococcal Enolase as Cariogenic Factor in Dental Disease 258
13.7 Conclusion 258
Acknowledgement 259
References 259
14 Streptococcal Enolase and Immune Evasion 269
Masaya Yamaguchi and Shigetada Kawabata
14.1 Introduction 269
14.2 Localization and Crystal Structure 271
Contents xi
14.3 Multiple Binding Activities of α‐Enolase 273
14.4 Involvement of α‐Enolase in Gene Expression Regulation 276
14.5 Role of Anti‐α‐Enolase Antibodies in Host Immunity 277
14.6 α‐Enolase as Potential Therapeutic Target 279
14.7 Questions Concerning α‐Enolase 281
References 281
15 Borrelia burgdorferi Enolase and Plasminogen Binding 291
Catherine A. Brissette
15.1 Introduction to Lyme Disease 291
15.2 Life Cycle 292
15.3 Borrelia Virulence Factors 292
15.4 Plasminogen Binding by Bacteria 293
15.5 B. burgdorferi and Plasminogen Binding 294
15.6 Enolase 295
15.7 B. burgdorferi Enolase and Plasminogen Binding 297
15.8 Concluding Thoughts 301
Acknowledgements 301
References 301
Part 3.5 Other Glycolytic Enzymes Acting as Virulence Factors 309
16 Triosephosphate Isomerase from Staphylococcus aureus
and Plasminogen Receptors on Microbial Pathogens 311
Reiko Ikeda and Tomoe Ichikawa
16.1 Introduction 311
16.2 Identification of Triosephosphate Isomerase on S. aureus
as a Molecule that Binds to the Pathogenic Yeast C. neoformans 312
16.2.1 Co‐Cultivation of S. aureus and C. neoformans 312
16.2.2 Identification of Adhesins on S. aureus and C. neoformans 312
16.2.3 Mechanisms of C. neoformans Cell Death 313
16.3 Binding of Triosephosphate Isomerase with Human
Plasminogen 314
16.4 Plasminogen‐Binding Proteins on Trichosporon asahii 314
16.5 Plasminogen Receptors on C. neoformans 316
16.6 Conclusions 316
References 317
17 Moonlighting Functions of Bacterial Fructose
1,6‐Bisphosphate Aldolases 321
Neil J. Oldfield, Fariza Shams, Karl G. Wooldridge, and David P.J. Turner
17.1 Introduction 321
17.2 Fructose 1,6‐bisphosphate Aldolase in Metabolism 321
17.3 Surface Localization of Streptococcal Fructose 1,6‐bisphosphate
Aldolases 322
17.4 Pneumococcal FBA Adhesin Binds Flamingo Cadherin Receptor 323
17.5 FBA is Required for Optimal Meningococcal Adhesion to 
Human Cells 324