The Comprehensive Sourcebook of Bacterial Protein Toxins

This book describes the major achievements and discoveries relevant to bacterial protein toxins since the turn of the new century illustrated by the discovery of more than fifty novel toxins (many of them identified through genome screening). The establishment of the three-dimensional crystal structure of more than 20 toxins during the same period offers deeper knowledge of structure-activity relationships and provides a framework to understand how toxins recognize receptors, penetrate membranes and interact with and modify intracellular substrates.

In Memoriam

Contributors

Preface to Third Edition

Preface to Second Edition

Preface to First Edition

Introduction

Chapter 1: A 116-year story of bacterial protein toxins (1888–2004): from “diphtheritic poison” to molecular toxinology

INTRODUCTION

REPERTOIRE OF BACTERIAL PROTEIN AND PEPTIDE TOXINS (1888–2004)

DISCOVERY OF THE FIRST BACTERIAL PROTEIN TOXINS: DIPHTHERIA, TETANUS, AND BOTULINAL TOXINS (1888, 1890, 1896)

TOXIN RESEARCH BETWEEN 1900 AND 1975

MAJOR ACHIEVEMENTS IN TOXIN RESEARCH FROM 1975 TO DATE

RATIONAL / CANONICAL CLASSIFICATION OF BACTERIAL TOXINS

CONCLUSION

SECTION I: BASIC GENOMIC AND PHYSIOLOGICAL ASPECTS OF BACTERIAL PROTEIN TOXINS

Chapter 2: Evolutionary aspects of toxin-producing bacteria

INTRODUCTION

MOLECULAR ECOLOGY OF TOXIN-PRODUCING BACTERIA

MOLECULAR EVOLUTION OF TOXINS THROUGH GENETIC EXCHANGE

CONCLUSION

Chapter 3: Mobile genetic elements and pathogenicity islands encoding bacterial toxins

INTRODUCTION: THE GENOME STRUCTURE OF PROKARYOTES

PROTEIN TOXINS ENCODED BY MOBILE GENETIC ELEMENTS

TOXINS ENCODED BY PATHOGENICITY ISLANDS

CONCLUSION

ACKNOWLEDGMENTS

Chapter 4: Regulation systems of toxin expression

INTRODUCTION

REGULATION OF VIRULENCE GENE EXPRESSION IN BACILLUS CEREUS

THE BORDETELLA BVGA/S SYSTEM

GENETIC REGULATION IN CLOSTRIDIA

GENETIC REGULATION OF STAPHYLOCOCCUS AUREUS EXOTOXINS

Chapter 5: Toxin secretion systems

INTRODUCTION

INNER MEMBRANE TRANSLOCATION

OUTER MEMBRANE TRANSLOCATION

CLOSING REMARKS

Chapter 6: Toxin receptors

GENERAL NOTES ON BACTERIAL TOXIN RECEPTORS

HOW DO YOU IDENTIFY BACTERIAL TOXIN RECEPTORS?

EXAMPLES OF TOXIN RECEPTORS

CONCLUSION

Chapter 7: Translocation of bacterial protein toxins into the cytosol

INTRODUCTION AND BRIEF DESCRIPTION OF RELEVANT TOXINS

BINDING TO CELL SURFACE RECEPTORS

ENDOCYTOSIS

RETROGRADE VESICULAR TRANSPORT

TRANSLOCATION TO THE CYTOSOL

STABILITY OF TOXINS IN THE CYTOSOL

TRANSLOCATION OF FUSION PROTEINS

ACKNOWLEDGMENTS

Chapter 8: Intracellular trafficking of bacterial and plant protein toxins

INTRODUCTION

GENERAL CONSIDERATIONS

CELL SURFACE RECEPTORS

MULTIPLE ENDOCYTIC PATHWAYS OPERATE IN MAMMALIAN CELLS

CLATHRIN-DEPENDENT ENDOCYTOSIS

CLATHRIN-INDEPENDENT PATHWAYS

INTRACELLULAR DISTRIBUTION PATHWAYS

RECYCLING OF TOXINS TO THE PLASMA MEMBRANE

TOXIN TRAFFICKING TO LATE ENDOSOMES/LYSOSOMES

THE RETROGRADE ROUTE

NON-CONVENTIONAL ENDOSOMAL PATHWAYS

CONCLUSION

ACKNOWLEDGMENTS

Chapter 9: Bacterial toxins and virulence factors targeting the actin cytoskeleton and intercellular junctions

INTRODUCTION

ACTIN CYTOSKELETON AND REGULATION OF ACTIN POLYMERIZATION

BACTERIAL PROTEIN TOXINS TARGETING ACTIN

TYPE-III SECRETION OF ACTIN ADP-RIBOSYLATING FACTORS

TOXINS INACTIVATING RHO-GTPASES

CLOSTRIDIAL GLUCOSYLATING TOXINS

TYPE-III VIRULENCE FACTORS WITH GAP ACTIVITY

OTHER TYPE-III VIRULENCE FACTORS INACTIVATING RHO-GTPASES

TOXINS ACTIVATING RHO-GTPASES

VIRULENCE FACTORS WITH GEF ACTIVITY

OTHER TOXINS MODIFYING ACTIN POLYMERIZATION

TOXINS TARGETING INTERCELLULAR JUNCTION MOLECULES

VIRULENCE FACTORS PROMOTING ACTIN NUCLEATION AND POLYMERIZATION

BACTERIAL REORGANIZATION OF ACTIN AND PHYSIOPATHOLOGICAL EFFECTS

CONCLUSION

Chapter 10: Bacterial toxins and mitochondria

INTRODUCTION

STRUCTURE AND BIOGENESIS OF MITOCHONDRIA

MITOCHONDRIA: ORGANELLES DEDICATED TO THE LIFE AND DEATH OF THE CELL

BACTERIAL TOXINS AND VIRULENCE FACTORS TARGETING MITOCHONDRIA

WHY DO BACTERIAL TOXINS AND VIRULENCE FACTORS TARGET MITOCHONDRIA?

CONCLUSION

ACKNOWLEDGMENTS

Chapter 11: Toxins activating Rho GTPases and exploiting the cellular ubiquitin/proteasome machineries

INTRODUCTION

THE FAMILY OF RHO GTPASE–ACTIVATING TOXINS

CNF1 AND DNT STRUCTURE/FUNCTION RELATIONSHIP

CELLULAR EFFECTS OF RHO ACTIVATION/DEGRADATION BY BACTERIAL TOXINS

ACKNOWLEDGMENTS

SECTION II: BACTERIAL PROTEIN TOXINS ACTING IN THE INTRACELLULAR COMPARTMENT OF EUKARYOTIC CELLS

Chapter 12: Molecular, functional, and evolutionary aspects of ADP-ribosylating toxins

INTRODUCTION

THE ENZYMATIC REACTION AND THE SUBSTRATES

CELL ENTRY

BACTERIAL TOXINS

EUKARYOTIC MONO-ADP-RIBOSYLTRANSFERASES

A COMMON STRUCTURE OF THE CATALYTIC SITE

Chapter 13: Diphtheria toxin

INTRODUCTION

GENETICS AND REGULATION OF DIPHTHERIA TOXIN PRODUCTION

STRUCTURE OF DIPHTHERIA TOXIN

DIPHTHERIA TOXIN RECEPTOR

INTERNALIZATION AND TRANSLOCATION OF DIPHTHERIA TOXIN

ACTIVITY OF DIPHTHERIA TOXIN AND INTRACELLULAR TARGET

DIPHTHERIA TOXIN AS A VACCINE COMPONENT

POTENTIAL MEDICAL USES OF THE DIPHTHERIA TOXIN R DOMAIN AND THE CELLULAR RECEPTOR

USES OF THE DIPHTHERIA TOXIN C AND T DOMAINS IN TREATMENT OF DISEASE

CONCLUSION

ACKNOWLEDGMENTS

Chapter 14: Pseudomonas aeruginosa toxins

INTRODUCTION

TYPE III SECRETION IN P. AERUGINOSA

DISCUSSION

CONCLUSION

Chapter 15: Vibrio cholerae and Escherichia coli thermolabile enterotoxin

INTRODUCTION

CHOLERA AND RELATED ENTEROPATHIES

STRUCTURE OF CHOLERA TOXIN AND RELATED ENTEROTOXINS

BIOGENESIS OF CHOLERA TOXIN AND RELATED ENTEROTOXINS

ACTION OF CHOLERA TOXIN AND RELATED ENTEROTOXINS IN MEDIATING DIARRHEA

CONCLUSION

ACKNOWLEDGMENTS

Chapter 16: Bordetella protein toxins

INTRODUCTION

PERTUSSIS TOXIN

ADENYLATE CYCLASE TOXIN

DERMONECROTIC TOXIN

Chapter 17: The Shiga toxins: properties and action on cells

INTRODUCTION

THE SHIGA TOXINS AND THE BACTERIA THAT PRODUCE THEM

DETECTION OF SHIGA AND SHIGA-LIKE TOXINS

BINDING OF TOXIN TO CELL SURFACE RECEPTORS

ENDOCYTIC UPTAKE OF SHIGA TOXIN

TRANSPORT OF STX BETWEEN ENDOSOMES AND THE GOLGI APPARATUS

RETROGRADE STX TRANSPORT TO THE ER AND TRANSLOCATION OF THE A-CHAIN TO THE CYTOSOL

TRANSPORT OF STX ACROSS EPITHELIAL CELLS

INDUCTION OF CYTOKINE PRODUCTION

TOXIN-INDUCED APOPTOSIS

PROTECTION AGAINST SHIGA TOXINS

EXPLOITATION OF SHIGA TOXIN IN MEDICINE

CONCLUSION

ACKNOWLEDGMENTS

Chapter 18: Bacillus anthracis toxins

INTRODUCTION

THE GENETICS OF TOXIN AND VIRULENCE

THE PROTEINS

TOXIN ACTION ON CELLS AND ANIMALS

CONCLUSION

Chapter 19: Attack of the nervous system by clostridial toxins: physical findings, cellular and molecular actions

INTRODUCTION

THE CELLULAR AND MOLECULAR MECHANISMS INVOLVED IN EXOCYTOSIS: AN OVERVIEW

BOTULINUM AND TETANUS NEUROTOXINS

OTHER TOXINS WITH DISTINCT NEUROTOXIC ACTIVITIES

ENTEROTOXINS AND THE ENTERIC NERVOUS SYSTEM

CONCLUSION

Chapter 20: Uptake and transport of Clostridium neurotoxins

INTRODUCTION

CLOSTRIDIUM NEUROTOXINS

STRUCTURE-FUNCTION RELATIONSHIP

INTERNALIZATION

AXONAL TRANSPORT IN SPINAL CORD MOTOR NEURONS

TRANSPORT OF CLOSTRIDIAL NEUROTOXINS

TRANSLOCATION OF CNT THROUGH VESICLE MEMBRANES

INTRACELLULAR ZINC-ENDOPEPTIDASE ACTIVITY

CLOSTRIDIUM NEUROTOXIN TARGETS

BASIS FOR CLOSTRIDIUM NEUROTOXIN RECOGNITION OF SNARE PROTEINS

PROTEIN AND GENE TRANSFER VIA TENT

CLOSTRIDIUM NEUROTOXINS AND SIGNALING

ACKNOWLEDGMENTS

Chapter 21: Large clostridial cytotoxins modifying small GTPases

INTRODUCTION

MOLECULAR BIOLOGY OF LARGE CLOSTRIDIAL TOXINS

STRUCTURAL AND FUNCTIONAL PROPERTIES OF LCTS

LARGE CLOSTRIDIAL CYTOTOXINS IN PATHOGENESIS

APPLICATION OF THE CYTOTOXINS AS TOOLS IN CELL BIOLOGY

ACKNOWLEDGMENTS

Chapter 22: Pasteurella multocida toxin

INTRODUCTION

PMT CHARACTERIZATION

PMT INTERACTION WITH AND ENTRY INTO MAMMALIAN CELLS

MOLECULAR AND CELLULAR MECHANISMS OF PMT ACTION

PMT STRUCTURE AND FUNCTIONAL ORGANIZATION

CONCLUSION

ACKNOWLEDGMENTS

Chapter 23: Cytolethal distending toxins

INTRODUCTION

ACTION OF CDT ON MAMMALIAN CELLS

CDTs AND DISEASE

CONCLUSION

ACKNOWLEDGMENTS

Chapter 24: Helicobacter pylori vacuolating toxin

INTRODUCTION

VacA SYNTHESIS AND GENETIC DIVERSITY

ROLE OF VacA IN VIVO

IN VITRO ACTIVITIES

VacA STRUCTURE AND FUNCTION

INTERACTIONS WITH HOST CELLS

VacA AS A VACCINE ANTIGEN

CONCLUSION

ACKNOWLEDGMENTS

Chapter 25: Escherichia coli heat-stable enterotoxin b

INTRODUCTION

STb POLYPEPTIDE

BIOCHEMICAL CHARACTERISTICS

DISULFIDE BOND FORMATION AND SECRETION OF STb

STb RECEPTOR

TOXIC DOMAIN AND 3D STRUCTURE OF STb

MECHANISM OF ACTION/MEDIATORS OF SECRETION

PORE FORMATION AND INTERNALIZATION OF STb

CONCLUSION

ACKNOWLEDGMENTS

SECTION III: TOXINS ACTING ON THE SURFACE OF TARGET CELLS (EXCEPT SUPERANTIGENS)

Chapter 26: Paradigms and classification of bacterial membrane-damaging toxins

INTRODUCTION

HISTORICAL BACKGROUND

GENERAL FEATURES OF THE MEMBRANE–DAMAGING TOXINS

PATHOGENIC EFFECTS OF MEMBRANE-DAMAGING TOXINS

CLASSIFICATION AND REPERTOIRE OF THE SUPERFAMILY OF MEMBRANE–DAMAGING TOXINS

THE CONCEPT OF TOXIN (PROTEIN)-INDUCED TRANSMEMBRANE PORES

TYPOLOGY OF PORE-FORMING TOXINS

CONCLUSION

Chapter 27: Membrane-damaging and cytotoxic phospholipases

INTRODUCTION

SUBSTRATES FOR PHOSPHOLIPASES

PHOSPHOLIPASES PRODUCED BY BACTERIA

ROLES OF PHOSPHOLIPASES IN DISEASE

INTERACTION OF PHOSPHOLIPASES WITH MEMBRANE PHOSPHOLIPIDS

THE MOLECULAR BASIS OF SUBSTRATE SPECIFICITY

VACCINES AND THERAPEUTIC APPLICATIONS OF PHOSPHOLIPASES

Chapter 28: Bacteroides fragilis toxins

INTRODUCTION

THE GENES AND PROTEIN STRUCTURE OF THE BACTEROIDES FRAGILIS TOXINS

MOLECULAR GENETICS OF ETBF

BIOLOGIC AND PHYSIOLOGIC ACTIVITIES OF THE BACTEROIDES FRAGILIS TOXINS

FUTURE CHALLENGES IN ETBF AND BFT RESEARCH

ACKNOWLEDGMENTS

Chapter 29: Structure and mode of action of RTX toxins

INTRODUCTION

GENERAL CHARACTERISTICS OF RTX TOXINS

MEMBERS OF THE RTX TOXIN FAMILY

PROPERTIES AND ACTIVITIES OF INDIVIDUAL RTX TOXINS

SPECIFIC ASPECTS OF THE STRUCTURE AND MODE OF ACTION OF RTX TOXINS

CONCLUSION

Chapter 30: Genetics and phylogeny of RTX cytolysins

INTRODUCTION

OPERON STRUCTURES

REGULATION OF GENE EXPRESSION OF RTX CYTOLYSINS

PHYLOGENY AND THE SPREAD OF RTX CYTOLYSIN GENES

CONCLUSION

Chapter 31: The family of two-component cytolysins of Serratia and other bacteria

INTRODUCTION

PHOSPHOLIPIDS ARE REQURED FOR ShlA ACTIVITY

ACTIVATION OF ShlA BY A CONFORMATIONAL CHANGE

SECRETION OF ShlA

THE TWO-PARTNER SECRETION (TPS) PATHWAY

ShlAB AND ITS HOMOLOGUES: COMPARATIVE GENOME ANALYSIS

INTERACTION OF ShlA WITH MEMBRANES

PORE FORMATION AND CYTOTOXICITY OF ShlA ON EUKARYOTIC CELLS

THE ROLE OF ShlA IN PATHOGENICITY

CYTOTOXICITY OF ShlA-RELATED HEMOLYSINS/CYTOTOXINS

CONCLUSION

Chapter 32: Alpha-helix and beta-barrel pore-forming toxins (leucocidins, alpha-, gamma-, and delta-cytolysins) of Staphylococcus aureus

INTRODUCTION

AN ALPHA-HELIX CYTOLYSIN PROTOTYPE: DELTA-HEMOLYSIN

A BETA-BARREL PORE-FORMING TOXIN PROTOTYPE: ALPHA-HEMOLYSIN

STAPHYLOCOCCAL BICOMPONENT LEUKOTOXINS

STAPHYLOCOCCAL PORE-FORMING TOXINS CHALLENGED IN PATHOGENESIS

APPLICATIONS AND ENGINEERED PORE-FORMING TOXINS IN PERSPECTIVE

CONCLUSION

ACKNOWLEDGMENTS

Chapter 33: Aerolysin and related Aeromonas toxins

INTRODUCTION

PRODUCTION, PURIFICATION, AND PRIMARY STRUCTURE

STRUCTURE OF PROAEROLYSIN

SECRETION OF PROAEROLYSIN

RECEPTOR BINDING

FROM THE PRECURSOR TO THE ACTIVE TOXIN

HEPTAMER FORMATION

MEMBRANE INSERTION AND CHANNEL PROPERTIES

CELLULAR CONSEQUENCES OF AEROLYSIN

AEROLYSIN AS A TOOL

CONCLUSION

ACKNOWLEDGMENTS

Chapter 34: Clostridium septicum pore-forming α-toxin

INTRODUCTION

MECHANISM OF ACTION AND STRUCTURE OF α-TOXIN

AT AND PATHOGENESIS

CONCLUSION

ACKNOWLEDGMENTS

Chapter 35: Clostridium perfringens ɛ-toxin

INTRODUCTION

-TOXIN

GENETIC ARRANGEMENT

SEQUENCE ANALYSIS OF -TOXIN

PATHOLOGY ASSOCIATED WITH INTOXICATION

NEUROTOXICITY

TOXICITY TOWARD CULTURED CELLS

THE -TOXIN STRUCTURE

COMPARISON OF -TOXIN AND AEROLYSIN

CONCLUSION

Chapter 36: Repertoire and general features of the family of cholesterol-dependent cytolysins

INTRODUCTION

REPERTOIRE OF THE CHOLESTEROL-DEPENDENT CYTOLYSINS

HISTORICAL BACKGROUND AND IDENTIFICATION OF CHOLESTEROL-DEPENDENT CYTOLYSINS

GENOMIC AND STRUCTURAL ASPECTS OF THE CHOLESTEROL-DEPENDENT CYTOLYSINS

PURIFICATION AND BIOCHEMICAL CHARACTERIZATION OF THE TOXINS

STEROL-BINDING PROPERTIES

CYTOLYTIC AND MEMBRANE-DAMAGING EFFECTS

ELECTRON MICROSCOPY STUDIES OF TOXIN INTERACTION WITH BIOLOGICAL AND ARTIFICIAL TARGET MEMBRANES

CONCLUSION

Chapter 37: Comparative three-dimensional structure of cholesterol-dependent cytolysins

INTRODUCTION

CDC PRIMARY STRUCTURES

PFO—AN ARCHETYPICAL CDC

CRYSTAL STRUCTURE OF PFO

STRUCTURE/FUNCTION STUDIES OF PFO

NEW CRYSTAL STRUCTURE OF PFO

MOLECULAR BASIS OF THIOL ACTIVATION

INTERMEDILYSIN—AN ATYPICAL CDC

CRYSTAL STRUCTURE OF ILY

STRUCTURAL COMPARISON OF ILY AND PFO

CHOLESTEROL-BINDING SITES

CONCLUSION

ACKNOWLEDGMENTS

Chapter 38: Perfringolysin O and intermedilysin: mechanisms of pore formation by the cholesterol-dependent cytolysins

INTRODUCTION

GENERAL FEATURES OF CDC STRUCTURE AND FUNCTIONAL MECHANISM

CHOLESTEROL INVOLVEMENT IN THE CDC CYTOLYTIC MECHANISM

THE ROLE OF DOMAIN 4 IN CDC PORE FORMATION

FORMATION OF THE PREPORE

PREPORE TO PORE CONVERSION

ROLE IN PATHOGENESIS

CONCLUSION

ACKNOWLEDGMENTS

Chapter 39: Pneumolysin: structure, function, and role in disease

INTRODUCTION

HISTORICAL

STRUCTURE AND FUNCTION STUDIES OF PLY

BIOLOGICAL EFFECTS OF PLY

THE ROLE OF PLY IN PATHOGENESIS

ASSAY OF ISOGENIC STRAINS IN VITRO

ASSAY OF ISOGENIC STRAINS IN VIVO: SYSTEMIC INFECTION

PNEUMONIA MODELS

REGULATION OF PLY EXPRESSION

USE OF PLY AS A VACCINE

CONCLUSION

ACKNOWLEDGMENTS

Chapter 40: Listeriolysin

INTRODUCTION

CHARACTERIZATION

STRUCTURE-FUNCTION

ROLE IN INTRACELLULAR PARASITISM

OTHER ROLES IN INFECTION

APPLICATIONS OF LLO RESEARCH

ACKNOWLEDGMENTS

Chapter 41: Enterococcus faecalis cytolysin toxin

BACKGROUND ON ENTEROCOCCI

PRE–MOLECULAR–ERA STUDIES OF CYTOLYSIN

THE CYTOLYSIN LOCUS

THE MOLECULAR COMPONENTS OF CYTOLYSIN

REGULATION OF CYTOLYSIN EXPRESSION

MOLECULAR MECHANISM OF CYTOLYSIN ACTIVITY

CYTOLYSIN AS A COLONIZATION AND VIRULENCE FACTOR

CONCLUSION

ACKNOWLEDGMENTS

Chapter 42: Streptolysin S: one of the most potent and elusive of all bacterial toxins

INTRODUCTION

GENERAL PROPERTIES AND PRODUCTION OF SLS

BIOCHEMISTRY OF SLS

MECHANISM OF ACTION

GENETIC BASIS OF SLS PRODUCTION

REGULATION

ROLE OF SLS IN DISEASE PATHOGENESIS

SLS PRODUCTION IN OTHER PATHOGENIC STREPTOCOCCI

CONCLUSION

Chapter 43: The group B streptococcal β-hemolysin/cytolysin

INTRODUCTION

BIOCHEMISTRY AND GENETICS

BIOLOGICAL EFFECTS

βH/C IN THE PATHOGENESIS OF GBS NEONATAL INFECTION

CONCLUSION

ACKNOWLEDGMENTS

Chapter 44: Hemolysins of vibrio cholerae and other vibrio species

INTRODUCTION

VIBRO CHOLERAE HEMOLYSINS

VIBRIO PARAHEMOLYTICUS HEMOLYSINS

VIBRIO VULNIFICUS HEMOLYSINS

VIBRIO MIMICUS HEMOLYSINS

OTHER VIBRIO HEMOLYSINS

CONCLUSION

Chapter 45: Clostridium perfringens enterotoxin

INTRODUCTION

THE GENETICS AND EXPRESSION OF CPE

THE INTESTINAL ACTION OF CPE

THE CELLULAR ACTION OF CPE

SUMMARY: A CURRENT MODEL FOR CPE ACTION

CPE STRUCTURE/FUNCTION RELATIONSHIPS

DEVELOPMENT OF A CPE VACCINE?

POTENTIAL THERAPEUTIC USE OF CPE

CONCLUSION

ACKNOWLEDGMENTS

Chapter 46: Bacillus cereus enterotoxins, bi- and tri-component cytolysins, and other hemolysins

INTRODUCTION: BACILLUS CEREUS SENSU LATO

BACILLUS CEREUS SENSU STRICTO

TOXINS OF B. CEREUS S.L.

REGULATION OF VIRULENCE FACTORS IN B. CEREUS S.L.

CONCLUSION

Chapter 47: Uropathogenic Escherichia coli cytolysins

INTRODUCTION

GENETICS OF α-HEMOLYSIN

REGULATION OF α-HEMOLYSIN EXPRESSION

ACTIVATION OF α-HEMOLYSIN

THE α-HEMOLYSIN SECRETION SYSTEM

RECEPTOR(S) AND MECHANISM(S) OF ACTION

CONCLUSION

Chapter 48: Escherichia coli, Vibrio, and Yersinia species heat-stable enterotoxins

INTRODUCTION

DISEASES CAUSED BY E. COLI, YERSINIA, AND VIBRIO

E. COLI STa ENTEROTOXIN

E. coli-EAST1 TOXIN

VIBRIO AND YERSINIA STs

CONCLUSION

SECTION IV: SUPERANTIGENIC TOXINS

Chapter 49: What are superantigens?

INITIAL INVESTIGATIONS

MAJOR FUNCTIONAL FEATURES OF SUPERANTIGENS

INTERACTION OF SAGS WITH IMMUNE SYSTEM CELLS

IMMUNOPATHOPHYSIO-LOGICAL PROPERTIES OF SAGS

REPERTOIRE OF BACTERIAL SUPERANTIGENS

STAPHYLOCOCCAL SUPERANTIGENS

STREPTOCOCCAL SUPERANTIGENS

CONCLUSION

ACKNOWLEDGMENTS

Chapter 50: Staphylococcal superantigens and the diseases they cause

INTRODUCTION

EMERGENCE OF STAPHYLOCOCCAL SAGS

SAG ACTIVITY AND T CELL-DEPENDENT PATHOGENIC ACTIVITY OF STAPHYLOCOCCAL TOXINS

INFECTIOUS DISEASES CAUSED BY STAPHYLOCOCCAL SAGS

CORRELATION BETWEEN THE LEVEL OF T CELL ACTIVATION AND CLINICAL SYMPTOM SEVERITY IN TSS AND NTED

Chapter 51: Streptococcal superantigenic toxins

INTRODUCTION

SUPERANTIGENS

GROUP A STREPTOCOCCAL SUPERANTIGENS

MOLECULAR BIOLOGY OF STREPTOCOCCAL SUPERANTIGENS

SUPERANTIGENS FROM NON-GAS

BIOCHEMICAL PROPERTIES OF SUPERANTIGENS

BIOLOGICAL AND PHARMACOLOGICAL ACTIVITIES

SUPERANTIGENS AND HUMAN DISEASE

ACKNOWLEDGMENTS

Chapter 52: The superantigenic toxin of Yersinia pseudotuberculosis

INTRODUCTION

YERSINIA PSEUDOTUBERCULOSIS, AN ENTEROPATHOGENIC BACTERIUM

Y. PSEUDOTUBERCULOSIS PRODUCES AN EXOTOXIN WITH SUPERANTIGEN ACTIVITY

THE THREE YPM VARIANTS ARE UNRELATED TO OTHER BACTERIAL SUPERANTIGENS

YPMA DISPLAYS A JELLY-ROLL FOLD

YPM IS CHROMOSOMALLY ENCODED

Y. PSEUDOTUBERCULOSIS IS THE ONLY PATHOGENIC YERSINIAE THAT PRODUCES SUPERANTIGENS

A SCENARIO FOR THE ACQUISITION OF YPM BY Y. PSEUDOTUBERCULOSIS

YPM IS A BACTERIAL VIRULENCE FACTOR

DOES YPM TRIGGER KAWASAKI DISEASE?

CONCLUSION

Chapter 53: Comparative three-dimensional structure of bacterial superantigenic toxins

INTRODUCTION

BINDING TO MHC CLASS II MOLECULES

BINDING TO THE T CELL RECEPTOR

OTHER STRUCTURAL FEATURES AND IDIOSYNCRASIES

FORMATION OF THE TRIMERIC COMPLEX FOR SIGNAL TRANSDUCTION

ACKNOWLEDGMENTS

SECTION V: CLINICAL, IMMUNOLOGICAL ASPECTS AND APPLICATIONS OF BACTERIAL PROTEIN TOXINS IN CELL BIOLOGY AND THERAPY

Chapter 54: Induction and modulation of inflammatory networks by bacterial protein toxins

INTRODUCTION

HELICOBACTER PYLORI –– GENERAL VIRULENCE MECHANISMS

CYSTIC FIBROSIS

ROLE OF BIOPROSTHETIC DEVICES AND BACTERIAL EXOPRODUCTS / TOXINS

CONCLUSION

ACKNOWLEDGMENTS

Chapter 55: Clostridial toxins in the pathogenesis of gas gangrene

INTRODUCTION

THE MAJOR HISTOTOXIC CLOSTRIDIAL INFECTIONS

THE ROLE OF EXOTOXINS IN C. PERFRINGENS GAS GANGRENE

CONCLUSION

ACKNOWLEDGMENTS

Chapter 56: Staphylococcal exfoliative toxins

INTRODUCTION

CLINICAL FEATURES

THE ORGANISM

THE EXFOLIATIVE TOXINS

FUTURE DIRECTIONS

CONCLUSION

Chapter 57: Bacterial toxins as food poisons

INTRODUCTION

THE FOOD-POISONING BACTERIA

THE TOXINS

CONCLUSION

Chapter 58: Medical applications of botulinum neurotoxins

INTRODUCTION

NEUROTOXIGENIC CLOSTRIDIA AND BOTULISM

BOTULINUM NEUROTOXIN STRUCTURE AND FUNCTION

PHARMACEUTIC BASIS OF BOTULINUM AND TETANUS TOXINS AS THERAPEUTIC AGENTS

HISTORICAL DEVELOPMENT OF BOTULINUM TOXIN AS A PHARMACEUTICAL

EFFECT OF BOTULINUM TOXIN COMPOSITION AND FORMULATION ON PHARMACEUTICAL EFFICACY

SAFETY IN WORKING WITH BoNTS AND TeNT

CLINICAL ASPECTS

CONCLUSION

Chapter 59: Toxins as tools

INTRODUCTION

PORE-FORMING TOXINS AS TOOLS

PROTEIN TOXINS TO STUDY GTP-BINDING PROTEINS

INACTIVATION OF RHO GTPases BY BACTERIAL PROTEIN TOXINS

RHO-ACTIVATING TOXINS

ADP-RIBOSYLATING TOXINS TO STUDY ACTIN

CLOSTRIDIAL NEUROTOXINS AS TOOLS TO STUDY EXOCYTOSIS

TOXINS FOR INTRACELLULAR PROTEIN DELIVERY

CONCLUSION

Chapter 60: Engineering of bacterial toxins for research and medicine

INTRODUCTION

ENGINEERING RECEPTOR-BINDING ACTIVITIES

ENGINEERING TOXIN ACTIVATION

EXPLOITING MEMBRANE BINDING AND TRANSLOCATION

ENGINEERING C DOMAINS

ENGINEERING OF ALPHA TOXIN FROM STAPHYLOCOCCUS AUREUS

CONCLUSION

Chapter 61: Engineered bacterial toxin vaccines and adjuvants

INTRODUCTION

CHOLERA TOXIN AND CHOLERA VACCINE DEVELOPMENT

TOXIN-BASED VACCINES AGAINST ENTEROTOXIGENIC ESCHERICHIA COLI (ETEC)

PERTUSSIS TOXIN AND DEVELOPMENT OF ACELLULAR PERTUSSIS VACCINE

DIPHTHERIA TOXIN CRM 197 AS CARRIER IN CONJUGATE VACCINES

CT AND LT AND DERIVATIVES AS MUCOSAL ADJUVANTS

DEVELOPMENT OF NON-TOXIC DERIVATIVES AS MUCOSAL ADJUVANTS

CT AND CTB AS ADJUVANTS FOR DENDRITIC CELL VACCINATION

CTB::CPG – A NOVEL POTENT IMMUNO-MODULATING ADJUVANT

Chapter 62: Bacterial protein toxins as biological weapons

INTRODUCTION: EVOLUTION OF BIOLOGICAL WEAPONRY

POST 9/11 ERA: THE U.S. RESPONSE TO BIOLOGICAL TERRORISM

BACTERIAL PROTEIN TOXINS AS BIOLOGICAL WEAPONS

CONCLUSION

Index

JA

Joseph E. Alouf

Joseph E. Alouf is Professor of Microbiology at the Pasteur Institute of Lille. He is former Head of the Department of Bacteriology and Mycology at the Pasteur Institute at Paris and Chairman of its Scientific Council. He served as Secretary General of the French Society of Immunology from 1984-1986 and President of the Federation of the European Microbiological Societies from 1989-1992. His 40-year research work relates to the field of bacterial protein toxins and immunology of infectious diseases. He is also the co-editor of several books.

Affiliations and expertise

Institute Pasteur de Lille, France

DL

Daniel Ladant

Daniel Ladant is Director of Research at French CNRS (National Center for Scientific Research) and head of the “Biochemistry of Macromolecular Interactions” unit at Institut Pasteur, Paris, France. He obtained a Ph.D. in Microbiology in 1989 and a « Habilitation à Diriger des Recherches » (HDR), in 1999 from the Université Paris Diderot, Paris, France. His research has been mainly focused on the study of the molecular mechanisms that underlie protein-protein and protein-membrane interactions, using as a model system a bacterial toxin, the adenylate cyclase (CyaA) produced by Bordetella pertussis, the causative agent of whooping cough. CyaA is an essential virulence factor from B. pertussis, and belongs to the large family of RTX (Repeat in ToXins) cytolysins produced by diverse Gram-negative bacteria. By combining molecular genetics, biochemical and biophysical approaches, he has characterized the structure, function and biogenesis of the CyaA toxin, with a particular emphasis on deciphering the molecular basis of its original entry pathway that involves a direct translocation of its catalytic domain across the plasma membrane. Basic knowledge gained on the mechanisms of CyaA entry into eukaryotic target cells and its interaction with cellular effectors has been used to develop various applications in vaccinology and biotechnology. In particular, the natural property of the CyaA toxin to target immune cells has been exploited to create innovative vaccines capable of stimulating potent cell-mediated immune responses against specific antigens. Two CyaA-based recombinant vaccines are currently evaluated in clinical trials. D. Ladant also designed a CyaA-based two-hybrid (BACTH) technology that has been exploited for studying, in bacteria, the assembly of protein complexes, and particularly to analyze membrane associated machineries such as bacterial secretion systems or the bacterial cell division apparatus. His other research interests include the other class II bacterial adenylate cyclase toxins, such as Edema Factor (EF) from Bacillus anthracis and ExoY toxin from Pseudomonas aeruginosa, in particular to explore of the allosteric mechanisms implicated in the activation of these enzymes by eukaryotic factors.

He has published more than 90 articles in peer-reviewed journals, 20 review articles or Book chapters and co-authored 11 patents.

Affiliations and expertise

PhD, Director of Research at French CNRS (National Center for Scientific Research) and head of the Biochemistry of Macromolecular Interactions unit at Institut Pasteur, Paris, France

MP

Michel R. Popoff

Michel R. Popoff, D.V.M., Ph.D. (Microbiology) from the University of Paris (1985), Habilitation à Diriger des Recherches (HDR) from the University of Paris (1990), is the Head of the Anaerobic Bacteria and Toxins Unit and the Director of the National Reference Center for Anaerobic Bacteria and Botulism at Pasteur Institute, Paris, France. He is member of the French Veterinary Academy. His laboratory is focused on Clostridium toxins through genetic and biological activity analysis and has investigated the regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani. In the recent years, we have analyzed the molecular mechanism of the actin depolymerizing C. sordellii lethal toxin and clostridial binary toxins, the pore-forming C. perfringens epsilon toxin, and the passage of botulinum neurotoxin through the intestinal barrier. He was co-editor of the 3° edition of the Sourcebook of Bacterial Protein Toxins Academic Press (2006).

Affiliations and expertise

CNR Anaerobies et Botulisme, Unite Bacteries anaerobies et Toxines, Institut Pasteur, FRANCE

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

The Comprehensive Sourcebook of Bacterial Protein Toxins

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Joseph E. Alouf

Michel R. Popoff

Joseph E. Alouf

Daniel Ladant

Michel R. Popoff