E-Book, Englisch, Band 53, 415 Seiten
Reihe: Subcellular Biochemistry
Wang / Quinn Endotoxins: Structure, Function and Recognition
1. Auflage 2010
ISBN: 978-90-481-9078-2
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark
E-Book, Englisch, Band 53, 415 Seiten
Reihe: Subcellular Biochemistry
ISBN: 978-90-481-9078-2
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark
Autoren/Hrsg.
Weitere Infos & Material
1;Frontispiece;7
2;Preface;8
3;Contents;10
4;Contributors;12
5;About the Editors;15
6;Part I Structure and Properties of Endotoxins;16
6.1;1 Endotoxins: Lipopolysaccharides of Gram-Negative Bacteria;17
6.1.1;1.1 Introduction;18
6.1.2;1.2 Biosynthesize of LPS on the Surfaces of Inner Membrane;19
6.1.2.1;1.2.1 Beginning in the Cytoplasm to Form Kdo2-Lipid A;19
6.1.2.2;1.2.2 Connecting the Core Oligosaccharides to Lipid A;22
6.1.2.3;1.2.3 Synthesizing the O-antigen at the Cytoplasmic Surface of the Inner Membrane;23
6.1.2.4;1.2.4 Crossing the Inner Membrane;23
6.1.2.5;1.2.5 Assembling LPS at the Periplasmic Surface of the Inner Membrane;24
6.1.3;1.3 Export of LPS to the Surface of Bacteria;25
6.1.4;1.4 Structural Modification of LPS;26
6.1.4.1;1.4.1 Regulation of LPS Modification;26
6.1.4.2;1.4.2 Modifications in the Hydrophobic Region of LPS;29
6.1.4.3;1.4.3 Modifications in the Hydrophilic Region of LPS;30
6.1.5;1.5 Conclusion;32
6.1.6;References;32
6.2;2 Purification and Characterization of Lipopolysaccharides;40
6.2.1;2.1 Introduction;41
6.2.2;2.2 Extraction of Lipopolysaccharides;41
6.2.2.1;2.2.1 Large Scale Extraction of Lipopolysaccharides;41
6.2.2.1.1;2.2.1.1 Phenol--Water Extraction;42
6.2.2.1.2;2.2.1.2 Ether Extraction;43
6.2.2.1.3;2.2.1.3 EDTA Promoted Extraction;44
6.2.2.2;2.2.2 Micro-extraction of Lipopolysaccharides;45
6.2.2.2.1;2.2.2.1 Phenol--Water Micro-extraction;45
6.2.2.2.2;2.2.2.2 Phenol--Chloroform Micro-extraction;46
6.2.2.3;2.2.3 Extraction of Lipid A;46
6.2.2.3.1;2.2.3.1 Extraction of Lipid A from LPS;46
6.2.2.3.2;2.2.3.2 Extraction of Lipid A from Bacteria;47
6.2.2.3.3;2.2.3.3 Micro-extraction of Lipid A;47
6.2.2.3.4;2.2.3.4 Extraction of Free Lipid A;49
6.2.3;2.3 Purification of Lipopolysaccharides;49
6.2.3.1;2.3.1 Removal of Contaminants;50
6.2.3.2;2.3.2 Gel Filtration Chromatography of LPS;51
6.2.3.3;2.3.3 Ion-Exchange Chromatography of LPS;52
6.2.3.4;2.3.4 Capillary Electrophoresis of LPS;52
6.2.3.5;2.3.5 Purification of Lipid A;52
6.2.3.6;2.3.6 Micro-purification Method;54
6.2.4;2.4 Analysis of Lipopolysaccharides;54
6.2.4.1;2.4.1 Electrophoresis of LPS;55
6.2.4.2;2.4.2 Staining Methods;56
6.2.4.2.1;2.4.2.1 Silver Stain;56
6.2.4.2.2;2.4.2.2 Ethidium Bromide Stain;57
6.2.4.2.3;2.4.2.3 Zinc-Imidazole Stain;57
6.2.4.3;2.4.3 Immunoblotting Method;58
6.2.4.4;2.4.4 Analysis of Lipid A;58
6.2.5;2.5 Conclusions;58
6.2.6;References;59
6.3;3 Endotoxins: Relationship Between Structure, Function,INTbreak; and Activity;65
6.3.1;3.1 Introduction;66
6.3.2;3.2 Physicochemical Characterisation of Endotoxins;66
6.3.3;3.3 Morphology and Size Distribution of Endotoxin Aggregates;69
6.3.4;3.4 Intramolecular Conformation;70
6.3.5;3.5 Biophysical Mechanisms of Agonism and Antagonism;72
6.3.6;3.6 Endotoxically Active Unit;74
6.3.7;References;76
6.4;4 The Diversity of the Core Oligosaccharide in Lipopolysaccharides;80
6.4.1;4.1 Introduction;81
6.4.2;4.2 Core Structures;86
6.4.2.1;4.2.1 Enterobacteria;86
6.4.2.2;4.2.2 Pasteurellaceae;90
6.4.2.3;4.2.3 Pseudomonas;92
6.4.2.4;4.2.4 Acinetobacter;94
6.4.2.5;4.2.5 Xanthomonas;95
6.4.2.6;4.2.6 Burkholderia;96
6.4.2.7;4.2.7 Ralstonia;98
6.4.2.8;4.2.8 Shewanella;98
6.4.2.9;4.2.9 Alteromonadaceae;99
6.4.2.10;4.2.10 Arenibacter Certesii;100
6.4.2.11;4.2.11 Psychromonas Arctica;101
6.4.2.12;4.2.12 Vibrionaceae;102
6.4.2.13;4.2.13 Rizhobiaceae;102
6.4.2.14;4.2.14 Loktanella Rosea;102
6.4.2.15;4.2.15 Halomonas Pantellerensis;104
6.4.3;4.3 Conclusion;105
6.4.4;References;105
6.5;5 Salmonella-Regulated Lipopolysaccharide Modifications;111
6.5.1;5.1 Introduction;112
6.5.1.1;5.1.1 Clinical Features and Relevance;112
6.5.1.2;5.1.2 Salmonella Pathogenesis;113
6.5.1.3;5.1.3 Host Defenses Against Salmonella Infection;115
6.5.1.4;5.1.4 Bacterial Modification of LPS and Other Surface Moieties;116
6.5.2;5.2 Two-Component Regulatory Systems;117
6.5.2.1;5.2.1 PhoP--PhoQ Regulatory System;119
6.5.2.2;5.2.2 PmrA--PmrB Regulatory System;120
6.5.2.3;5.2.3 RcsC--RcsD--RcsB Regulatory System;122
6.5.3;5.3 Additional Bacteria Capable of Modifying LPS;124
6.5.4;5.4 Summary and Significance;124
6.5.5;References;125
6.6;6 The Variation of O Antigens in Gram-Negative Bacteria;133
6.6.1;6.1 Introduction;134
6.6.2;6.2 O Serotyping Schemes;135
6.6.2.1;6.2.1 Conventional O Serotyping Methods;135
6.6.2.2;6.2.2 Molecular Typing Methods;136
6.6.2.2.1;6.2.2.1 PCR-RFLP;136
6.6.2.2.2;6.2.2.2 Gene-Specific PCR;137
6.6.2.2.3;6.2.2.3 DNA Microarray;137
6.6.3;6.3 O antigen Diversity in Gram-Negative Bacteria;138
6.6.3.1;6.3.1 Enterobacteriaceae;138
6.6.3.1.1;6.3.1.1 Escherichia and Shigella;138
6.6.3.1.2;6.3.1.2 Salmonella ;139
6.6.3.1.3;6.3.1.3 Yersinia ;139
6.6.3.1.4;6.3.1.4 Citrobacter ;140
6.6.3.1.5;6.3.1.5 Klebsiella ;140
6.6.3.1.6;6.3.1.6 Serratia ;140
6.6.3.1.7;6.3.1.7 Hafnia ;141
6.6.3.1.8;6.3.1.8 Proteus ;141
6.6.3.2;6.3.2 Pseudomonadaceae;141
6.6.3.2.1;6.3.2.1 P. aeruginosa ;142
6.6.3.2.2;6.3.2.2 P. syringae ;142
6.6.3.3;6.3.3 Vibrionaceae;142
6.6.4;6.4 General Properties of O Antigen Gene Clusters;142
6.6.4.1;6.4.1 O Antigen Biosynthesis;143
6.6.4.2;6.4.2 Examples of O Antigen Gene Clusters;145
6.6.4.2.1;6.4.2.1 E. coli, S. enterica and Shigella spp;145
6.6.4.2.2;6.4.2.2 Enterobacter Sakazakii;146
6.6.4.2.3;6.4.2.3 P. aeruginosa;146
6.6.4.2.4;6.4.2.4 V. cholerae;146
6.6.4.2.5;6.4.2.5 Yersinia;147
6.6.4.2.6;6.4.2.6 Legionella Pneumophila;148
6.6.4.2.7;6.4.2.7 C. freundii;148
6.6.5;6.5 Formation and Distribution of O Antigen Gene Clusters;148
6.6.5.1;6.5.1 Lateral Transfer of O Antigen Genes by Homologous Recombination;149
6.6.5.2;6.5.2 Insertion and Deletion of O Antigen Genes Mediated by IS Elements;150
6.6.5.3;6.5.3 Role of Plasmids in Evolution of O Antigen gene Clusters;150
6.6.5.4;6.5.4 O Antigen Modification Mediated by Phages;151
6.6.6;6.6 O antigen and Virulence;153
6.6.6.1;6.6.1 The Complete Loss of O Antigen Leads to Severe Attenuation of Virulence;153
6.6.6.2;6.6.2 The O Antigen Differences Can Account for Differences in the Nature of Pathogenicity;153
6.6.6.3;6.6.3 The Effect of the Chemical Composition and Structure of an O Side Branch on Virulence;154
6.6.6.4;6.6.4 The O Antigen Chain Lengths is Important for the Full Virulence;154
6.6.7;6.7 Conclusions;155
6.6.8;References;155
6.7;7 Regulators of TLR4 Signaling by Endotoxins;163
6.7.1;7.1 Introduction;164
6.7.2;7.2 TLR4 Signaling Pathway;165
6.7.2.1;7.2.1 MyD88-Dependent Pathway;166
6.7.2.2;7.2.2 MyD88-Independent Pathway;168
6.7.3;7.3 Localisation of TLR4 and its Adaptor Molecules;168
6.7.4;7.4 Chaperones;169
6.7.5;7.5 Negative Regulators of TLR4 Signaling;170
6.7.5.1;7.5.1 Cell Surface Receptors;170
6.7.5.2;7.5.2 Splice Variants;171
6.7.5.3;7.5.3 Inhibitory Molecules;172
6.7.5.3.1;7.5.3.1 IRAK-M;172
6.7.5.3.2;7.5.3.2 TRAF1 and TRAF4;172
6.7.5.3.3;7.5.3.3 TANK;173
6.7.5.3.4;7.5.3.4 RIP3;173
6.7.5.3.5;7.5.3.5 A20;173
6.7.5.3.6;7.5.3.6 SOCS-1;174
6.7.5.3.7;7.5.3.7 Rab7b;175
6.7.6;7.6 Conclusion;175
6.7.7;References;175
6.8;8 Membrane Partitioning: Is Location Everything When It Comes to Endotoxin Recognition?;182
6.8.1;8.1 Introduction;183
6.8.2;8.2 The Innate Immune System;183
6.8.2.1;8.2.1 The Toll Like Receptor Family;184
6.8.2.2;8.2.2 Innate Immune Recognition of Bacterial Endotoxin or Lipopolysaccharide;185
6.8.2.3;8.2.3 Protein--Protein Interactions in Innate Immunity: PRRs Are Part of Multi-component Sensor Apparatuses;186
6.8.2.4;8.2.4 Is TLR4 Recruited in Membrane Microdomains Upon Ligand Engagement?;187
6.8.2.5;8.2.5 Does Membrane-Partitioning Play a Major Role in Protein Uptake and Intracellular Routing?;188
6.8.2.6;8.2.6 Concluding Remarks;189
6.8.3;References;190
7;Part II Infection, Treatment and Immunity;194
7.1;9 Endotoxin Detection from Limulus Amebocyte Lysate to Recombinant Factor C;195
7.1.1;9.1 General Introduction;196
7.1.2;9.2 Gram-Negative Bacterial Membrane A Wall of Fire;197
7.1.3;9.3 Lipopolysaccharide: A Mediator of Septic Shock Pathophysiological Properties;197
7.1.4;9.4 The Structure of LPS;198
7.1.4.1;9.4.1 The O-Specific Chain;198
7.1.4.2;9.4.2 The Core Oligosaccharide Domain;199
7.1.4.3;9.4.3 The Lipid A;200
7.1.5;9.5 Plasma LPS-Binding Proteins Protect and Provoke Septic Shock The Achilles Heel?;201
7.1.6;9.6 Overcoming the LPS Problem The Horseshoe Crab, a Creature Small and Great;204
7.1.7;9.7 Drawbacks with LAL;206
7.1.7.1;9.7.1 Differential Endotoxin Reactivities and Lack of Specificity;206
7.1.7.2;9.7.2 Problems with Sample and Specimen Preparations;207
7.1.7.3;9.7.3 LAL Production Endangers the Horseshoe Crab;207
7.1.8;9.8 Factor C: A Horseshoe Crab Serine Protease with Multiple High Affinity LPS-Binding Sites LPS Detection and Prevention Strategies Towards Non-LAL Based LPS Detection;208
7.1.9;9.9 Genetic Engineering and Production of Recombinant Factor C (rFC) Necessity Spawns Innovation: Cloning and Subcloning the Factor C cDNA into Bacterial, Yeast, Insect and Mammalian Cells;208
7.1.10;9.10 Development of a Quantitative Endotoxin Assay;209
7.1.11;9.11 Commercialization of the Endotoxin Detection Kit The Route to PyroGene and Pyrosense;210
7.1.12;References;211
7.2;10 The Role of Endotoxin in Infection: Helicobacter pylori and Campylobacter jejuni ;217
7.2.1;10.1 Introduction;218
7.2.1.1;10.1.1 Helicobacter pylori and Campylobacter jejuni Infections;218
7.2.1.2;10.1.2 Nature of H. pylori and C. jejuni Endotoxins;219
7.2.2;10.2 Structure and Properties of H. pylori and C. jejuni Lipid A Moieties;221
7.2.2.1;10.2.1 Structural Analysis of H. pylori Lipid A;221
7.2.2.2;10.2.2 Structural Analysis of C. jejuni Lipid A;223
7.2.2.3;10.2.3 Molecular and Supramolecular Basis for the Contrasting Immunological Activities of C. jejuni and H. pylori Lipid A Moieties;224
7.2.3;10.3 Relevance of Low Endotoxin and Lipid A Immuno-Activities to Chronic Infection: H. pylori as a Comparative Model;225
7.2.4;10.4 Molecular Mimicry in H. pylori Endotoxin;227
7.2.4.1;10.4.1 H. pylori Expression of Lewis (Le) and Blood Group Antigen Mimicry;227
7.2.4.2;10.4.2 Anti-Le Antibodies in Autoimmune Pathogenesis;229
7.2.4.2.1;10.4.2.1 Anti-Le Antibodies and the Inflammatory Response;229
7.2.4.2.2;10.4.2.2 Anti-Le Antibodies in Gastric Atrophy;230
7.2.5;10.5 Molecular Mimicry in C. jejuni Endotoxin;232
7.2.5.1;10.5.1 Expression of Gangliosiode Mimicry by C. jejuni;232
7.2.5.2;10.5.2 Pathogenic Anti-Ganglioside Antibodies and C. jejuni Ganglioside Mimicry;235
7.2.5.2.1;10.5.2.1 Pathogenic Anti-Ganglioside Antibodies in GBS;235
7.2.5.2.2;10.5.2.2 T-Cells in GBS Development;236
7.2.5.2.3;10.5.2.3 C. jejuni Ganglioside Mimicry and Anti-Ganglioside Antibodies;236
7.2.5.3;10.5.3 Relevance of Molecular Mimicry in the Pathogenesis of GBS;237
7.2.5.3.1;10.5.3.1 Galway Postulates;237
7.2.5.3.2;10.5.3.2 Experimental Models;238
7.2.6;10.6 Conclusions and Future Perspective;239
7.2.7;References;240
7.3;11 The Role of Pseudomonas Lipopolysaccharide in Cystic Fibrosis Airway Infection;249
7.3.1;11.1 Introduction;250
7.3.2;11.2 Cystic Fibrosis is an Important Disease of Children and Young Adults;250
7.3.2.1;11.2.1 Persistent Inflammation and Chronic Infection are the Hallmarks of CF Pulmonary Disease;251
7.3.2.2;11.2.2 P. aeruginosa Is an Important Pathogen in the CF Airway;252
7.3.2.3;11.2.3 Adaptation of P. aeruginosa to the Airway Is Important for CF Lung Disease;252
7.3.2.4;11.2.4 P. aeruginosa Lipid A Structures in CF Clinical Isolates are Distinct from Those Seen in Acute Clinical Infections and Isolates from the Environment;252
7.3.2.5;11.2.5 Synthesis of Cystic Fibrosis-Specific Lipid A Modifications in P. aeruginosa;255
7.3.2.6;11.2.6 P. aeruginosa Lipid A Modifications Promote CAP Resistance;256
7.3.2.7;11.2.7 P. aeruginosa Lipid A Modifications Modulate Host Inflammatory Responses;258
7.3.3;11.3 Conclusions;259
7.3.4;References;259
7.4;12 Development of Small-Molecule Endotoxin Sequestering Agents;262
7.4.1;12.1 Introduction;263
7.4.2;12.2 Endotoxin, the Trigger in Gram-Negative Sepsis;264
7.4.2.1;12.2.1 Host Responses to Endotoxin;264
7.4.2.2;12.2.2 Complexation of LPS by Macromolecules: A Failed Therapeutic Strategy?;267
7.4.2.3;12.2.3 The Paradigm of Non-Immunologic Sequestration of LPS by Small Molecules: A More Accessible Strategy?;267
7.4.3;12.3 Lipopolyamines as Endotoxin Sequestrants;269
7.4.3.1;12.3.1 Further SAR Lessons Learned En Route to DS-96, an N-Alkylhomospermine Lipopolyamine;275
7.4.3.2;12.3.2 Activity of DS-96 in Human Blood;279
7.4.3.3;12.3.3 In Vivo Potency, Pharmacodynamics and Pharmacokinetics of DS-96;279
7.4.3.4;12.3.4 Toxicity of DS-96;279
7.4.3.5;12.3.5 Pharmacokinetics of DS-96 and Further Developments;283
7.4.4;12.4 Conclusions and Future Prospects;284
7.4.5;References;285
7.5;13 Development of an Anti-Endotoxin Vaccine for Sepsis;291
7.5.1;13.1 Introduction;292
7.5.2;13.2 Endotoxin as a Therapeutic Target;292
7.5.3;13.3 Endotoxin Structure and Immunity;293
7.5.4;13.4 Initial Studies of Anti-LPS Core Antibodies as Therapy for Gram-Negative Bacterial Infections;295
7.5.4.1;13.4.1 Anti-Core LPS Antibody Levels;297
7.5.4.2;13.4.2 Anti-Lipid A Antibodies;297
7.5.5;13.5 Anti Core Monoclonal Antibodies;298
7.5.6;13.6 Development of J5 Subunit Vaccine;298
7.5.6.1;13.6.1 Initial Studies with Unadjuvanted Vaccine;299
7.5.6.2;13.6.2 J5 dLPS/OMP Vaccine and Adjuvants;301
7.5.7;13.7 Other Anti-Endotoxin Vaccines;301
7.5.8;13.8 Immunization Strategies with Anti-Endotoxin Vaccines;303
7.5.9;13.9 Other Potential Applications of Anti-Endotoxin Vaccine;303
7.5.10;References;304
7.6;14 Synthetic and Natural TLR4 Agonists as Safe and Effective Vaccine Adjuvants;309
7.6.1;14.1 Introduction;310
7.6.2;14.2 Immune Recognition of Lipopolysaccharide (LPS) and Related Molecules;314
7.6.3;14.3 Lipid A Structure and Activity;315
7.6.4;14.4 Formulation Effects on TLR4 Agonist Activity;317
7.6.5;14.5 Conclusion;322
7.6.6;References;323
7.7;15 Targeting Endotoxin in the Treatment of Sepsis;328
7.7.1;15.1 Introduction;329
7.7.2;15.2 Endotoxin and the Initiation of the Sepsis Cascade;329
7.7.3;15.3 Rationale for Targeting Endotoxin in Sepsis;330
7.7.4;15.4 Potential for Targeting Endotoxin in Sepsis;331
7.7.5;15.5 Anti-Endotoxin Antibodies;331
7.7.6;15.6 Vaccines;333
7.7.7;15.7 Endotoxin-Binding Peptides;333
7.7.7.1;15.7.1 Bactericidal/Permeability Increasing Protein;333
7.7.7.2;15.7.2 Human Lactoferrin;334
7.7.8;15.8 Lipid A Analog;334
7.7.9;15.9 Phospholipid Emulsion;335
7.7.10;15.10 Hemoperfusion Through a Polymixin B Embedded Cartridge;335
7.7.10.1;15.10.1 Animal Studies;336
7.7.10.2;15.10.2 Human Studies;337
7.7.11;15.11 Conclusion;338
7.7.12;References;338
7.8;16 Lipopolysaccharides in Rhizobium-Legume Symbioses;344
7.8.1;16.1 Introduction;345
7.8.2;16.2 Rhizobial Lipopolysaccharide Structures;347
7.8.2.1;16.2.1 Lipid A (LA) Structures;348
7.8.2.2;16.2.2 Core Oligosaccharide (COS) Structures;350
7.8.2.3;16.2.3 O-Chain Polysaccharide (OPS) Structures;354
7.8.3;16.3 Rhizobial Lipopolysaccharide Biosynthesis;359
7.8.3.1;16.3.1 LA Biosynthesis;359
7.8.3.2;16.3.2 Core Biosynthesis;364
7.8.3.3;16.3.3 O-Chain Polysaccharide Synthesis;366
7.8.4;16.4 Structural Modifications to Rhizobial LPSs During Symbiosis;371
7.8.4.1;16.4.1 Modifications to the O-Chain Polysaccharide During Symbiosis;372
7.8.4.2;16.4.2 Modifications to the Core Oligosaccharide During Symbiosis;376
7.8.4.3;16.4.3 Modifications to the LA During Symbiosis;376
7.8.5;16.5 Rhizobial Lipopolysaccharide Function;377
7.8.5.1;16.5.1 The Symbiotic Function of the Unique Structural Features and Modifications of Rhizobial Lipopolysaccharides;377
7.8.5.2;16.5.2 Rhizobial Lipopolysaccharide, Symbiosis, and the Plant Defense Response;380
7.8.6;References;382
7.9;17 Lipopolysaccharides and Plant Innate Immunity;392
7.9.1;17.1 Introduction;393
7.9.2;17.2 LPS as a M394
7.9.2.1;17.2.1 LPS as a Direct Inducer of Basal Plant Defenses;394
7.9.2.2;17.2.2 LPS as a Primer of Plant Defense Response Induction;395
7.9.2.3;17.2.3 LPS can Modulate the Hypersensitive Response, a Programmed Cell Death Associated with Resistance;395
7.9.2.4;17.2.4 LPS Induces Systemic Effects in Plants;396
7.9.3;17.3 Different Sub-Structures Within LPS can Act as MAMPs;397
7.9.4;17.4 Structural Variations in LPS Influence its Activity in Plants;398
7.9.5;17.5 Subversion of LPS-Induced Effects;399
7.9.6;17.6 Perception of LPS by Plants;399
7.9.6.1;17.6.1 SNARE Proteins, Vesicle Trafficking and Plant Defense;400
7.9.6.2;17.6.2 A Role for the Syntaxin PEN1 in LPS Signalling in Plants?;401
7.9.7;17.7 Concluding Remarks;403
7.9.8;References;404
8;Index;409




