Bacterial Protein Toxins

by Aktories, Klaus; Just, Ingo

ISBN13: 9783540661252

ISBN10: 3540661255

Format: Hardcover

Pub. Date: 2000-06-01

Publisher(s): Springer Verlag

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Summary

In recent years remarkable progress has been accomplished with respect to our knowledge about bacterial protein toxins. This refers especially to structural aspects of protein toxins but also holds true for genetics, molecular biology and biochemical mechanisms underlying the action of toxins. This volume covers the very current and exciting aspects of up-to-date bacterial toxicology and comprehensively reviews the most important bacterial protein toxins such as the intracellular acting toxins which exhibit enzyme activity, as well as those toxins that interact with cell plasma membranes by damaging the membranes (pore formation) or stimulating cell receptors (superantigens). This is the most current reference work on these important bacterial protein toxins, which are presented from the point of view of different disciplines such as pharmacology, microbiology, cell biology and protein chemistry.

Uptake of Protein Toxins Acting Inside Cells

(20)

S. Olsnes

J. Wesche

P.O. Falnes

Introduction and Brief Description of Relevant Toxins

(3)

Binding to Cell-Surface Receptors

(1)

Endocytosis

(2)

Retrograde Vesicular Transport

(1)

Transport to the Golgi Apparatus

(1)

Transport to the Endoplasmic Reticulum

(1)

Translocation to the Cytosol

(3)

From the Surface

(1)

From Endosomes

(1)

From the ER

(2)

Stability of Toxins in the Cytosol

(1)

Translocation of Fusion Proteins

(9)

References

(7)

Common Features of ADP-Ribosyltransferases

(24)

V. Masignani

M. Pizza

R. Rappuoli

Introduction

(1)

The Well-Characterized Toxins

(5)

A Common Structure for the Catalytic Site

(7)

Region 1

(2)

Region 3

(1)

Region 2

(3)

Other Bacterial Toxins with ADP-Ribosylating Activity

(2)

Eukaryotic Mono-ADP-Ribosyltransferases

(2)

Practical Applications

(8)

References

(6)

Diphtheria Toxin and the Diphtheria-Toxin Receptor

(22)

T. Umata

K.D. Sharma

E. Mekada

Introduction

(1)

Diphtheria Toxin

(6)

Synthesis of Diphtheria Toxin

(1)

Toxicity of Diphtheria Toxin

(2)

Structure and Function of Diphtheria Toxin

(1)

The Catalytic Domain

(1)

The T Domain

(1)

The R Domain

(1)

Sensitivity to Diphtheria Toxin

(1)

The Diphtheria-Toxin Receptor

(16)

Identification of the Diphtheria-Toxin-Receptor Protein

(1)

Cloning of the Diphtheria-Toxin-Receptor Gene

(1)

The Structure and Function of the Diphtheria-Toxin Receptor

(2)

Molecules Associated with the Diphtheria-Toxin Receptor

(1)

DRAP27/CD9

(2)

Heparin-Like Molecules

(1)

Receptor and Toxin Entry Process

(1)

Physiological Role of the Diphtheria-Toxin Receptor

(1)

EGF-Family Growth Factor

(1)

Juxtacrine Growth Regulator

(1)

Conversion of the Membrane-anchored Form to the Soluble Form

(1)

References

(6)

Pseudomonas aeruginosa Exotoxin A: Structure/Function, Production, and Intoxication of Eukaryotic Cells

(24)

S.E.H. West

Introduction

(4)

Basic Structure

(2)

Role of ETA in Disease

(1)

Production of ETA by the Bacterial Cell

(5)

Characterization of the toxA Structural Gene

(1)

Environmental and Temporal Signals Affecting ETA Production

(1)

Regulation of ETA Production

(3)

Secretion from the Bacterial Cell

(1)

Intoxication of Eukaryotic Cells

(15)

Binding to a Specific Receptor on the Eukarvotic Cell Surface and Internalization by Receptor-Mediated Endocytosis

(2)

Activation by Proteolytic Cleavage and/or a Conformational Change

(1)

Removal of a Terminal Lysine Residue and Translocation into the Cytosol

(1)

ADP-Ribosylation of Elongation Factor 2

(2)

References

(9)

Diphtheria-Toxin-Based Fusion-Protein Toxins Targeted to the Interleukin-2 Receptor: Unique Probes for Cell Biology and a New Therapeutic Agent for the Treatment of Lymphoma

(18)

J.R. Murphy

J.C. Vanderspek

Introduction

(1)

Diphtheria-Toxin-Based Cytokine Fusion Proteins

(4)

DAB389IL-2 as a Novel Biological Probe for Cell Biology

(2)

Pre-Clinical Characterization of DAB486IL-2 and DAB389IL-2

(1)

Clinical Evaluation of DAB486IL-2 and DAB389IL-2

(11)

Rheumatoid Arthritis

(1)

Psoriasis

100

(1)

Non-Hodgkin's Lymphoma

101

(1)

Cutaneous T-Cell Lymphoma

102

(2)

References

104

(5)

Structure and Function of Cholera Toxin and Related Enterotoxins

109

(24)

F. Van Den Akker

E. Merritt

W.G.J. Hol

Introduction

109

(1)

Three-Dimensional Structures of Holotoxins

110

(2)

Toxin Assembly and Secretion

112

(1)

Design of Assembly Antagonists

113

(1)

Cell-Surface-Receptor Recognition

113

(2)

Design of Receptor Anatagonists

115

(1)

Toxin Internalization

115

(2)

Enzymatic Mechanism

117

(3)

Substrates, Artificial Substrates, and Inhibitors

117

(2)

NAD-Binding Site

119

(1)

The LT-II Family

120

(5)

Perspectives

125

(8)

References

125

(8)

Mechanism of Cholera Toxin Action: ADP-Ribosylation Factors as Stimulators of Cholera Toxin-Catalyzed ADP-Ribosylation and Effectors in Intracellular Vesicular Trafficking Events

133

(34)

W.A. Patton

N. Vitale

J. Moss

M. Vaughan

Introduction

133

(2)

Cholera Toxin

135

(2)

Structure

135

(1)

Biochemistry

135

(1)

Toxin Internalization

136

(1)

ADP-Ribosylation Factors

137

(15)

Discovery of ARFs

137

(1)

Biochemical Characterization of ARFs

138

(1)

ARF Structure

139

(1)

The Primary Structures of ARFs

139

(1)

The Tertiary Structures of ARFs

140

(1)

Other ARF Family Members

141

(1)

ARF-Related Proteins

141

(2)

ARF-Domain Protein 1

143

(2)

Molecules that Regulate ARF Function: GEPs and GAPs

145

(1)

ARF Guanine Nucleotide-Exchange Proteins

145

(2)

ARF GTPase-Activating Proteins

147

(2)

Other ARF-Interacting Molecules

149

(1)

Phospholipase D

149

(1)

Arfaptins

150

(1)

ARF in Cells

150

(1)

ARFs' Role in Vesicular Trafficking Events

150

(1)

Subcellular Localization of ARF

151

(1)

Summary

152

(15)

References

152

(15)

Pertussis Toxin: Structure-Function Relationship

167

(20)

C. Locht

R. Antoine

A. Veithen

D. Raze

Introduction

167

(1)

The Receptor-Binding Activity of PTX

168

(2)

Membrane Translocation of PTX

170

(5)

The Enzymatic Activity of S1

175

(1)

The Enzyme Mechanism of S1-Catalyzed ADP-Ribosylation

176

(2)

The Catalytic Residues of PTX

178

(2)

Substrate Binding by PTX

180

(2)

Conclusions

182

(5)

References

182

(5)

Pertussis Toxin as a Pharmacological Tool

187

(20)

B. Nurnberg

Introduction

187

(2)

Molecular Aspects of PT Activity on G Proteins

189

(6)

General Considerations

189

(1)

PT-Sensitive G Proteins

190

(1)

Mechanism of PT Action

190

(1)

G-Protein Specificity

191

(2)

PT as a Tool with which to Study G-Protein-Subunit Composition

193

(2)

Functional Consequences of PT Activity

195

(12)

PT-Affecting Receptor-G-Protein-Effector Coupling

195

(2)

PT-Affecting Receptor-Independent Activation of G Proteins

197

(1)

Use of PT in Studying Cellular Signal Transduction

198

(1)

Appendix: Experimental Protocols for Using PT

199

(1)

Source of PT and Preparation of Solutions

199

(1)

Treatment of Mammalian Cell Cultures with PT

199

(1)

Activation of PT for in Vitro ADP-Ribosylation

199

(1)

ADP-Ribosylation of Cell-Membrane Proteins by PT

200

(1)

ADP-Ribosylation of Isolated Proteins by PT

200

(1)

Preparation of Samples for Sodium Dodecyl Sulfate Polyacrylamide-Gel Electrophoresis

200

(1)

Cleavage of ADP-Ribose from Gα Subunits

201

(1)

References

201

(6)

Clostridium Botulinum C3 Exoenzyme and C3-Like Transferases

207

(28)

K. Aktories

H. Barth

I. Just

Introduction

207

(1)

Origin and Purification of C3 Exoenzymes

207

(2)

Origin of C3 Exoenzymes

207

(1)

Purification of C3 Exoenzymes

208

(1)

Genetics of C3 and C3-Like Exoenzymes

209

(1)

Structure-Function Analysis of C3 Exoenzymes

210

(2)

ADP-Ribosyltransferase Activity

212

(6)

Basic Properties

212

(1)

Regulation by Detergents and Divalent Cations

212

(1)

Rho Proteins as Substrates for C3

213

(2)

Functional Consequences of the ADP-Ribosylation of Rho

215

(3)

Application of C3-Like Exoenzymes as Tools

218

(1)

Cellular Effects of C3 Exoenzymes

219

(5)

Effects of C3 on Cell Morphology and Actin Structure

219

(3)

Effects of C3 on Cell-Cell Contacts

222

(1)

Effects of C3 on Endocytosis and Phagocytosis

223

(1)

Effects of C3 on Cell Signalling not Directly Involving the Actin Cytoskeleton

223

(1)

Phospholipase D and PIP5 Kinase

223

(1)

Signalling to the Nucleus and Gene Transcription

224

(1)

Concluding Remarks

224

(11)

References

225

(10)

Pseudomonas aeruginosa Exoenzyme S, a Bifunctional Cytotoxin Secreted by a Type-III Pathway

235

(18)

J.T. Barbieri

D.W. Frank

Introduction

235

(1)

Initial Biochemical Characterization of ExoS

236

(1)

Genetic Analysis of the Structural Genes Encoding ExoS

236

(1)

ExoS Requires FAS to Express ADP-Ribosyltransferase Activity

237

(1)

Molecular Properties of ExoS

237

(2)

Secretion of ExoS via a Type-III Secretion Pathway

239

(1)

Regulation of exoS Regulation Expression

240

(1)

The Carboxyl Terminus of ExoS Comprises the ADP-Ribosyltransferase Domain

240

(4)

Functional Mapping of ExoS

240

(1)

ExoS is a Biglutamic-Acid Transferase

240

(2)

ExoS can ADP-Ribosylate Numerous Proteins

242

(1)

ExoS ADP-Ribosylates Ras at Multiple Arginine Residues

243

(1)

ExoS is a Bifunctional Cytotoxin

244

(2)

Cytotoxic Properties of ExoS

245

(1)

The Amino Terminus of ExoS Stimulates Rho-Dependent Depolymerization of Actin

245

(1)

The Carboxyl Terminus of ExoS is an ADP-Ribosyltransferase that is Cytotoxic to Cultured Cells

246

(1)

Mechanism for the Inhibition of Ras-Mediated Signal Transduction by ExoS

246

(1)

Functional and Sequence Relationship Between ExoS and the Vertebrate ADP-Ribosyltransferases

247

(1)

Conclusion

248

(5)

References

248

(5)

Structure and Function of Actin-Adenosine-Diphosphate-Ribosylating Toxins

253

(22)

I. Ohishi

Introduction

253

(1)

Clostridium Botulinum C2 Toxin

253

(9)

Actin-ADP-Ribosylating Toxin of C. Botulinum Types C and D

253

(1)

Molecular Structure of Botulinum C2 Toxin

254

(2)

Molecular Functions of Two Components of C2 Toxin

256

(1)

ADP-Ribosylation of Actin by C2 Toxin

257

(1)

ADP-Ribosylation of Intracellular Actin of Cultured Cells

258

(2)

ADP-Ribosylation of Purified Actin

260

(2)

C. Perfringens Iota Toxin

262

(3)

Actin-ADP-Ribosylating Toxin of C. Perfringens Type E

262

(1)

Molecular Structure and Function

263

(2)

C. Spiroforme Toxin

265

(1)

Actin-ADP-Ribosylating Toxin of C. Spiroforme

265

(1)

Molecular Structure and Function

265

(1)

C. Difficile Toxin

266

(2)

Actin-ADP-Ribosylating Toxin of C. Difficile

266

(1)

Molecular Structure and Function

266

(2)

Concluding Remarks

268

(7)

References

269

(6)

Molecular Biology of Actin-ADP-Ribosylating Toxins

275

(32)

M.R. Popoff

Introduction

275

(1)

Bacteria Producing Actin-ADP-Ribosylating Toxins

276

(1)

C. Botulinum

276

(1)

C. Perfringens

276

(1)

C. Spiroforme

277

(1)

C. Difficile

277

(1)

Families of Actin-ADP-Ribosylating Toxins

277

(5)

C2-Toxin Family

278

(1)

Iota-Toxin Family

279

(1)

Relatedness Between C2-Toxin and Iota-Toxin Families

279

(3)

Actin-ADP-Ribosylating-Toxin Genes and Predicted Molecules

282

(2)

Iota-Toxin Genes and Iota-Toxin Proteins

282

(1)

C. Spiroforme Toxin and CDT Genes

283

(1)

C. Spiroforme Toxin and CDT Proteins

283

(1)

C2-Toxin Genes and C2 Proteins

284

(1)

Relatedness of Actin-ADP-Ribosylating Toxins with Other Toxins

284

(8)

Relatedness with ADP-Ribosylating Toxins

284

(4)

Relatedness with Bacillus anthracis Toxins

288

(1)

Sequence Homology

288

(1)

Immunological Relatedness

289

(1)

Functional Comparison

289

(1)

Relatedness with Other Binary Toxins

290

(1)

Bacillus Binary Toxins

290

(1)

Leukocidins and γ-Lysins

291

(1)

Genetics of the Actin-ADP-Ribosylating Toxins

292

(2)

Genomic Localization

292

(1)

Gene Transfer

293

(1)

Gene Expression

294

(3)

Genes of Enzymatic and Binding-Component Genes are Organized in an Operon

294

(1)

Gene Regulation

295

(2)

Identification of Actin-ADP-Ribosylating-Toxin-Producing Clostridia by Genetic Methods

297

(1)

Functional Domains

297

(5)

Enzymatic-Component Domains

297

(1)

Enzymatic Site

297

(2)

Enzymatic-Component Domain which Interacts with the Binding Component

299

(1)

Actin-Binding Site

300

(1)

Binding-Component Domains

300

(2)

Concluding Remarks

302

(5)

References

302

(5)

Molecular Mechanisms of Action of the Large Clostridial Cytotoxins

307

(26)

I. Just

F. Hofmann

K. Aktories

Introduction

307

(1)

Structure of the Toxins

308

(1)

Cell Entry

309

(6)

Molecular Mode of Action

315

(12)

Elucidation of the Molecular Mechanism of Action

315

(1)

Enzymatic Activity

316

(1)

Co-Substrates

316

(2)

Catalytic Domain and Requirements for Catalysis

318

(2)

Recognition of the Protein Substrates

320

(1)

Cellular Targets of the Cytotoxins

321

(1)

Rho and Ras Proteins as Substrates

321

(1)

Site of Modification

321

(1)

Cellular Functions of Rho Proteins

322

(2)

Functional Consequences of Glucosylation

324

(1)

Consequences on the GTPase Cycle

324

(1)

Biological Consequences

325

(2)

Concluding Remarks

327

(6)

References

327

(6)

Molecular Biology of Large Clostridial Toxins

333

(28)

J.S. Moncrief

D.M. Lyerly

T.D. Wilkins

Introduction

333

(2)

Purification and Characterization of Large Clostridial Toxins

335

(6)

Toxin Production

335

(1)

Purification and Physicochemical Properties

336

(1)

C. Difficile Toxins

336

(1)

C. Sordellii and C. Novyi Toxins

337

(1)

Biological Properties

337

(1)

C. Difficile Toxins

337

(2)

C. Sordellii and C. Novyi Toxins

339

(1)

Receptors

340

(1)

Mechanism of Action

341

(1)

Molecular Genetics of the Toxins

342

(7)

C. Difficile Toxin A and B Genes

342

(2)

C. Difficile Toxigenic Element

344

(1)

Atypical Strains of C. Difficile

344

(1)

C. Sordellii and C. Novyi Genes

345

(1)

Sequence Identity and Conserved Features of the Toxins

346

(1)

N-Terminal Glucosyltransferase Domain

346

(1)

Repeating Units

347

(1)

Additional Conserved Features

348

(1)

Gene Transfer in C. Difficile

349

(1)

Regulation of C. Difficile Toxins

349

(2)

Conclusions

351

(10)

References

351

(10)

The Cytotoxic Necrotizing Factor 1 from Escherichia Coli

361

(24)

P. Boquet

C. Fiorentini

Introduction

361

(1)

The CNF1 Gene and the Prevalence of CNF1-Producing Strains among Uropathogenic E. coli

362

(2)

The CNF1 Gene

362

(1)

Prevalence of CNF1-Producing Strains among Uropathogenic E. coli

363

(1)

Production, Purification and Cellular Effects of E. coli CNF1

364

(1)

Production and Purification of E. coli CNF1

364

(1)

Cellular Effects of E. coli CNF1

365

(1)

CNF1 Molecular Mechanism of Action

365

(8)

Intracellular Enzymatic Activity of CNF1

365

(3)

Consequences of CNF1 Activity on Rho GTP-Binding Proteins

368

(5)

Structure-Function Relationships of CNF1 and the Family of Dermonecrotic Toxins

373

(2)

The C-Terminal Part of CNF1 Contains its Enzymatic Activity

373

(2)

The N-Terminal Part of CNF1 Contains its Cell-Binding Activity

375

(1)

Possible Roles for CNF1 as a Virulence Factor

375

(4)

CNF1 and Induction of Phagocytosis

375

(2)

CNF1 and Cell Apoptosis

377

(1)

CNF1: Epithelial Cell Permeability and PMN Trans-Epithelial Migration

378

(1)

Conclusions

379

(6)

References

379

(6)

Shiga Toxins of Shigella dysenteriae and Escherichia coli

385

(22)

A.R. Melton-Celsa

A.D. O'Brien

Profile of the Shiga-Toxin Family

385

(4)

Nomenclature and History

385

(1)

The Stx Family

386

(1)

Traits that Make the Members Part of a Family

386

(1)

Characteristics that Distinguish Stx Family Members

387

(1)

Role of Stxs in S. Dysenteriae Type 1 and STEC Disease

388

(1)

Pathogenesis of Infection Caused by Organisms that Produce Stxs

388

(1)

Associations Between Stxs and Development of HC and/or the HUS

388

(1)

Findings with Animal and Tissue Culture Models that Support a Primary Role for Stxs in Virulence of Shiga's Bacillus and STEC

389

(1)

Stx Genetics and Expression

389

(3)

Location, Organization, and Nucleotide and Deduced Amino Acid Sequences of Stx Family Member Operons

389

(2)

Regulation of Toxin Production

391

(1)

Toxin Purification

391

(1)

Structure-Function Analyses of Stx Family Members

392

(4)

Structure of Stx

392

(1)

Genetic Analyses of Stx Function

393

(3)

Intracellular Trafficking of the Shiga Toxins

396

(1)

Virulence/Toxicity Differences among the Stxs

397

(1)

Immune Response to Stxs, Passive Anti-Stx Therapy, and Vaccine Development

397

(2)

Anti-Toxin Responses during STEC Infection

397

(1)

Passive Therapy with Anti-Stx Antibodies

398

(1)

Vaccine Development

398

(1)

Summary

399

(8)

References

399

(8)

Clostridial Neurotoxins

407

(38)

H. Bigalke

L.F. Shoer

Introduction

407

(2)

Tetanus and Botulism in Man and Animals

409

(3)

Modes of Poisoning

409

(1)

Clinical Manifestations

410

(1)

Pathophysiology

410

(2)

Structure of Clostridial Neurotoxins

412

(5)

Genetic Determination

412

(1)

Structure of Proteins

413

(4)

Toxicokinetics of Clostridial Neurotoxins

417

(5)

Receptor Binding and Internalization

417

(2)

Translocation from Endosomes into the Cytosol and Priming

419

(2)

Sorting, Routing and Axonal Transport

421

(1)

Toxicodynamics of Clostridial Neurotoxins

422

(5)

Mode of Action of Clostridial Neuroproteases

422

(3)

Function of Substrates

425

(2)

Clostridial Neurotoxins serve as Tools in Cell Biology and as Therapeutic Agents

427

(18)

References

431

(14)

Anthrax Toxin

445

(28)

S.H. Leppla

Introduction

445

(1)

Toxin Genes

446

(1)

Gene Location and Organization

446

(1)

DNA Sequences and Transcriptional Regulation

446

(1)

Toxin-Component Proteins

447

(9)

Toxin Production, Purification, and Properties

447

(1)

PA Structure and Function

448

(4)

LF Structure and Function

452

(2)

EF Structure and Function

454

(1)

PA Family Members

455

(1)

Cellular Uptake and Internalization

456

(6)

Cellular Receptor for PA

456

(1)

Proteolytic Activation of PA

456

(1)

LF and EF Binding to PA63

457

(1)

Endocytic Uptake

458

(1)

Channel Formation

459

(2)

Translocation and Cytosolic Trafficking

461

(1)

Intracellular Actions

462

(2)

EF Adenylate Cyclase

462

(1)

LF Metalloprotease

463

(1)

Therapeutic Applications of LF Fusion Proteins

464

(1)

Summary and Future Prospects

465

(8)

References

465

(8)

Adenylyl-Cyclase Toxin from Bordetella pertussis

473

(16)

E.L. Hewlett

M.C. Gray

Introduction and Background

473

(1)

Gene and Protein Structure

474

(1)

Biological Activities of AC Toxin

475

(5)

Enzymatic Activity

475

(1)

Cell-Invasive Activity

476

(1)

Pore Formation and Hemolysis

477

(2)

Summary

479

(1)

Possible Role/s for AC Toxin in Pathogenesis

480

(1)

AC toxin as a Protective Antigen

481

(1)

Uses of AC Toxin as a Novel Research Reagent

482

(1)

Future Directions

482

(7)

References

483

(6)

Helicobacter Pylori Vacuolating Cytotoxin

489

(20)

W. Fischer

R. Haas

Introduction

489

(1)

Identification and Purification of the H. pylori Vacuolating Cytotoxin

490

(1)

Gene Structure and Mechanism of Secretion

491

(4)

Cloning and Molecular Characterisation of vacA Encoding the Vacuolating Cytotoxin

491

(2)

Autotransporter Organisation of the VacA Precursor

493

(1)

Mosaic Gene Structure of vacA Alleles in the H. pylori Population

493

(1)

Consequences of the vacA Mosaic Gene Structure

494

(1)

Presence of vacA Homologues in the H. pylori Genome

494

(1)

Regulation of vacA Gene Expression

495

(1)

Extracellular Structure and Activation of the Vacuolating Cytotoxin

496

(1)

Processing and Quaternary Structure

496

(1)

Activation by Acid

496

(1)

Effects of VacA on Eucaryotic Cells

497

(5)

Binding to Target Cells and Mechanism of Uptake

497

(2)

Vacuole Formation

499

(2)

Other Effects of VacA

501

(1)

Clinical Relevance of the Vacuolating Cytotoxin

502

(1)

VacA as a Vaccine Candidate

503

(1)

Concluding Remarks

503

(6)

References

504

(5)

Staphylococcal α Toxin

509

(20)

S. Bhakdi

I. Walev

M. Palmer

A. Valeva

Occurrence and Biological Significance

509

(1)

Purification and Properties of Monomeric Toxin

509

(1)

Mechanism of Action

510

(2)

Binding

510

(1)

Oligomerization

511

(1)

Pore Formation

512

(1)

Structure of Oligomeric Pores

512

(5)

Structure of the Heptameric Pore Formed in Detergent Solution

512

(2)

Structure of the Membrane-Bound Oligomer

514

(3)

Biological Effects

517

(3)

Cytocidal Action

517

(1)

Secondary Cellular Reactions

517

(1)

Reactions Provoked by Transmembrane Flux of Monovalent Ions

517

(1)

Ca2+-Dependent Reactions

518

(2)

Long-Range Effects of α Toxin

520

(1)

Synergism Between α Toxin and Other Toxins

520

(1)

Resistance and Repair Mechanism

520

(2)

Use of α Toxin in Cell Biology

522

(1)

Medical Relevance of α Toxin

523

(6)

References

524

(5)

Bacterial Phospholipases

529

(28)

R.W. Titball

J.I. Rood

Introduction

529

(1)

Related Groups of Phospholipases

529

(7)

Zinc Metallophospholipase Cs

530

(5)

Gram-Negative PLCs

535

(1)

Phosphatidylinositol PLCs

535

(1)

Phospholipase Ds

536

(1)

Functional and Biological Properties of Phospholipases

536

(2)

Modulation of Eukaryotic Cell Metabolism

538

(4)

Hydrolysis of Membrane Phospholipids

538

(3)

Hydrolysis of Membrane Phospholipids Modulates Cell Metabolism

541

(1)

Regulation

542

(2)

Regulation of the C. perfringens plc gene

542

(1)

Environmental Control of PLC Production in P. aeruginosa

542

(1)

Regulation of the Listeria Phospholipases by PrfA

543

(1)

Role in Disease

544

(4)

Gas Gangrene

544

(2)

P. aeruginosa Infections

546

(1)

The Pathogenesis of Listeriosis

547

(1)

Caseous Lymphadenitis in Ruminants

548

(1)

Conclusions

548

(9)

References

549

(8)

Pore-Forming Toxins as Cell-Biological and Pharmacological Tools

557

(20)

G. Ahnert-Hilger

I. Pahner

M. Holtje

Permeabilized Cells: an Approach to the Study of Intracellular Processes

557

(2)

α-Toxin and SLO as Tools with which to Study Functional Aspects of Intracellular Organelles

559

(13)

Biological Activity and Cell Permeability

559

(1)

Protocol 1: Permeabilization of Attached Cells by α-Toxin or SLO

560

(1)

Alternate Protocol 1

560

(1)

Protocol 2: Permeabilization of Cells in Suspension

560

(1)

Commentary for Protocols 1 and 2

561

(1)

Protocol 3: Assay to Compare Biological Activity of Various Pore-Forming Toxins Using Rabbit Erythrocytes

561

(1)

Commentary for Protocol 3

562

(1)

Protocol 4: Trypan-Blue Exclusion Test

562

(1)

Commentary for Protocol 4

563

(1)

Introduction of Membrane Impermeable Proteins

563

(2)

Protocol 5: Introduction of Membrane-Impermeable Proteins. Immunofluorescence for Synaptophysin

565

(1)

Commentary for Protocol 5

565

(1)

Protocol 6: Introduction of Membrane-Impermeable Proteins. TeNT/LC

566

(1)

Commentary for Protocol 6

567

(1)

Assay for Exocytosis in Permeabilized Cells

567

(1)

Protocol 7: Measuring Exocytosis in Permeabilized Suspension Cells

568

(2)

Protocol 8: Measuring Exocytosis in Permeabilized Attached Cells

570

(1)

Commentary for Basic Protocols 7 and 8

570

(1)

Regulation of Vesicular Transmitter Transporters in Permeabilized Cells

570

(1)

Protocol 9: Regulation of Vesicular Transmitter Transporters in Permeabilized Cells

571

(1)

Commentary for Basic Protocol 9

572

(1)

Chemicals Used in the Protocols

572

(1)

Concluding Remarks

573

(4)

References

573

(4)

Heat-Stable Enterotoxin of Escherichia Coli

577

(18)

T. Hirayama

A. Wada

Introduction

577

(1)

Heat-Stable Enterotoxin STa

578

(7)

Structure and Biological Properties of STa

578

(2)

Receptor for STa

580

(5)

STa-Like Heat-Stable Enterotoxin

585

(1)

Heat-Stable Enterotoxin STb

585

(3)

Structure of STb

585

(1)

Biological Function of STb

586

(2)

Concluding Remarks

588

(7)

References

588

(7)

Superantigenic Toxins

595

(24)

B. Fleischer

Summary

595

(1)

Introduction

595

(1)

PETs of S. Aureus and S. Pyogenes

596

(11)

Genes and Molecules

596

(4)

Molecular Mechanism of Action

600

(1)

Binding to MHC class-II Molecules

600

(1)

Non-MHC Receptors

601

(1)

Interaction with the TCR

602

(2)

Biological Significance of PETs

604

(1)

Role of PETs as Virulence Factors

604

(1)

Role in Pathogenesis

604

(1)

Association with Human Autoimmune Disease

605

(1)

The Enterotoxic Activity

606

(1)

Other Superantigens (or Pseudosuperantigens) of Gram-Positive Cocci?

607

(3)

The ETs of S. Aureus

607

(1)

M Proteins and SPE B of S. Pyogenes

607

(1)

The Mitogenic Factor of S. Pyogenes

608

(2)

The M. Arthritidis Superantigen

610

(1)

The Y. Pseudotuberculosis Mitogen

610

(1)

Concluding Remarks

611

(8)

References

611

(8)

Structure and Activity of Endotoxins

619

(50)

S. Hauschildt

W. Brabetz

A.B. Schromm

L. Hamann

P. Zabel

E.T. Rietschel

S. Muller-Loennies

Introduction

619

(5)

The Chemical Structure of LPS

624

(8)

Structural Characteristics of the O-Specific Chain

627

(1)

Structural Characteristics of the LPS Core

627

(2)

Structural Characteristics of Lipid A

629

(3)

Biosynthesis of LPS

632

(2)

Biosynthesis of Lipid A

632

(1)

Biosynthesis of the Core Region

632

(1)

Biosynthesis of the O-Specific Chain

633

(1)

Structure-Activity Relationships of LPS and Lipid A

634

(2)

Cellular and Humoral Responses to LPS in Mammals

636

(8)

Strategies for the Treatment of Gram-Negative Infections

644

(7)

Antibacterial Agents

645

(2)

Antagonists of Endotoxic Effects

647

(2)

Neutralizing Antibodies Against Endotoxin

649

(2)

Final Remarks

651

(18)

References

652

(17)

Translocated Toxins and Modulins of Yersinia

669

(22)

M. Aepfelbacher

R. Zumbihl

K. Ruckdeschel

B. Rouot

J. Heesemann

Introduction

669

(1)

Yersinia Protein Type-III Secretion/Translocation System

670

(4)

Virulence Plasmid pYV

670

(1)

Regulation of Yop Expression, Secretion and Translocation

671

(3)

Translocated Toxins and Modulins of Yersinia (Effector Yops)

674

(9)

YopH, a Highly Active Tyrosine Phosphatase

674

(3)

YopE, an Actin-Disrupting Cytotoxin

677

(1)

YopP, Modulator of Multiple Signal Pathways Leading to Apoptosis and Cytokine Suppression

678

(3)

YopT, Another Actin-Disrupting Cytotoxin

681

(1)

YopM-So Far, no Evidence for an Intracellular Function

681

(1)

YpkA, a Putative Serine/Threonine Kinase Affecting Cell Shape

682

(1)

Perspectives

683

(8)

References

685

(6)

Subject Index

691

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