Table Of ContentToxinology
P. Gopalakrishnakone Editor-in-Chief
Brad Stiles · Alberto Alape-Girón
J. Daniel Dubreuil · Manas Mandal Editors
Microbial
Toxins
Toxinology
Editor-in-Chief
P.Gopalakrishnakone
In recent years, the field of toxinology has expanded substantially. On one hand it
studies venomous animals, plants and microorganisms indetailto understand their
mode of action on targets. While on the other, it explores the biochemical compo-
sition, genomics and proteomics of toxins and venoms to understand their interac-
tions with life forms (especially humans), development of antidotes and exploring
their pharmacological potential. Therefore, toxinology has deep linkages with bio-
chemistry, molecular biology, anatomy and pharmacology. In addition, there is a
fast-developing applied subfield, clinical toxinology, which deals with understand-
ing and managing medical effects of toxins on the human body. Given the huge
impact of toxin-based deaths globally, and the potential of venom and toxin in
generation of drugs for so-far incurable diseases (for example, diabetes, chronic
pain),thecontinuedresearchandgrowthofthefieldisimminent.Thishasledtothe
growth of research in the area and the consequent scholarly output by way of
publications in journals and books. Despite this ever-growing body of literature
within biomedical sciences, there is still no all-inclusive reference work available
thathousesalloftheimportantbiochemical,biomedicalandclinicalinsightsrelating
to toxinology. Composed of 12 volumes, Toxinology provides comprehensive and
authoritativecoverageofthemainareasintoxinology,fromfundamentalconceptsto
new developments and applications in the field. Each volume comprises a focused
andcarefullychosencollectionofcontributionsfromleadingnamesinthesubject.
SeriesTitles
1. BiologicalToxinsandBioterrorism
2. ClinicalToxinologyintheAsiaPacificandAfrica
3. SpiderVenoms
4. ScorpionVenoms
5. MarineandFreshwaterToxins
6. VenomGenomicsandProteomics
7. SnakeVenoms
8. EvolutionofVenomousAnimalsandTheirVenoms
9. MicrobialToxins
10. PlantToxins
11. ToxinsandDrugDiscovery
12. ClinicalToxinologyinAustralia,Europe,andAmericas
Moreinformationaboutthisseriesisathttp://www.springer.com/series/13330
P. Gopalakrishnakone
Editor-in-Chief
(cid:129)
Brad Stiles Alberto Alape-Girón
(cid:129)
J. Daniel Dubreuil Manas Mandal
Editors
Microbial Toxins
With77Figuresand16Tables
Editor-in-Chief
P.Gopalakrishnakone
YongLooLinSchoolofMedicine
NationalUniversityofSingapore
Singapore,Singapore
Editors
BradStiles AlbertoAlape-Girón
BiologyDepartment DepartmentofBiochemistry
WilsonCollege SchoolofMedicineandInstitutoClodomiro
Chambersburg,Pennsylvania,USA Picado,FacultyofMicrobiology
UniversityofCostaRica
SanPedrodeMontesdeOca,CostaRica
J.DanielDubreuil ManasMandal
DepartmentofPathologyandMicrobiology CollegeofPharmacy
UniversitédeMontréal RosemanUniversityofHealthSciences
Saint-Hyacinthe,Québec,Canada Henderson,Nevada,USA
ISBN978-94-007-6448-4 ISBN978-94-007-6449-1(eBook)
ISBN978-94-007-6450-7(printandelectronicbundle)
https://doi.org/10.1007/978-94-007-6449-1
LibraryofCongressControlNumber:2017951719
#SpringerScience+BusinessMediaB.V.2018
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Series Preface
The term TOXIN is derived from the Greek word Toeikov and is defined as a
substance derived from tissues of a plant, animal, or microorganism that has a
deleterious effect on other living organisms. Studying their detailed structure,
function, and mechanism of action as well as finding an antidote to these toxins is
thefieldofTOXINOLOGY,andthescientistsarecalledTOXINOLOGISTS.
Inrecentyears,thefieldoftoxinologyhasexpandedsubstantially.Ononehand,it
studiesvenomousanimals,plants,andmicroorganismsindetailtounderstandtheir
habitat,distribution,identification,aswellasmodeofactionontargets,whileonthe
other,itexploresthebiochemicalcomposition,genomics,andproteomicsoftoxins
andvenomstounderstandtheirinteractionwithlifeforms(especiallyhumans),the
development of antidotes, and their pharmacological potential for drug discovery.
Therefore, toxinology has deep linkages with biochemistry, molecular biology,
anatomy,pharmacologyanddrugdevelopment.Inaddition,thereisafastdevelop-
ingappliedsubfield,clinicaltoxinology,whichdealswith understandingandman-
aging medical effects of venoms and toxins on the human body following
envenomations. Given the huge impact of envenomation-based deaths globally,
and the potential of venom and toxin in the generation of drugs for debilitating
diseases(e.g.,diabetes,chronicpain,andcancer),thecontinuedresearchandgrowth
ofthefieldisimminent.
Springerhastakentheboldinitiativeofproducingthisseries,whichisnotaneasy
task of generating 12 volumes, namely, biological toxins and bioterrorism, clinical
toxinology,scorpionvenoms,spidervenoms,snakevenoms,marineandfreshwater
toxins, toxins and drug discovery, venom genomics and proteomics, evolution of
venomousanimalsandtheirtoxins,planttoxins,andmicrobialtoxins.
Singapore P.Gopalakrishnakone
M.B.B.S.,Ph.D.,F.A.M.S.,D.Sc.
Editor-in-Chief
v
Acknowledgments
Iwouldliketosincerelythankthesectioneditorsofthisvolume,BradStiles,Alberto
Alape-Girón,J.DanielDubreuilandManasMandalfortheinvaluablecontribution
of their expertise and time and the authors who obliged with my request and
providedacomprehensivereviewonthetopics.
Springerprovidedsubstantialtechnicalandadministrativehelpbymanyindivid-
ualsatvaryinglevels,butspecialmentionshouldgotoSarahMathews,SunaliMull,
MeghnaSingh,MokshikaGaur,andAudreyWongfortheirtirelesseffortinbringing
thesevolumestoreality.
Singapore P.Gopalakrishnakone
M.B.B.S.,Ph.D.,F.A.M.S.,D.Sc.
Editor-in-Chief
vii
Volume Preface
This volume provides an overview of microbial toxins from diverse bacterial and
fungal origins. These molecules, produced by various species and consisting of
protein or small organic molecules, can play a pivotal role in the pathogenesis of
plants,animals,andhumansthatinturncanleadtothesurvival/disseminationofthe
hostmicrobe.Manyofthesemicrobes,duetotheirtoxins,impactoursocietyfroma
health and economic perspective. In particular, this volume addresses the diverse
niches of these organisms focused upon their associated toxins. The structures,
functions, and genetics of these toxins will be addressed. Besides the ill-effects
elicitedbythesetoxins,itmustbenotedthatthereisimmensepotentialforturning
someoftheseharmfulmolecules intousefultoolssuchasspecificreceptorprobes,
noveldrugsordrug-conjugatesforthetreatmentofvariousdiseases,andimmunomo-
dulating agents for targeted vaccine delivery. Recent progress in bacterial genome
mappingandestablishmentofthree-dimensionalcrystalstructuresofseveralbacte-
rial toxins provides a deeper knowledge and greater understanding of structure-
function relationships. Moreover, the emergence of some bacteria such as Bacillus
anthracis,Burkholderiapseudomallei,andStaphylococcusaureus,andtheirtoxins,
as biological weapons also necessitates a thorough understanding of these agents,
theirpathophysiology,anddevelopmentofcountermeasures.Thisvolumewillalso
serve as a common resource for researchers interested in many other medically
relevant microorganisms, and their toxins, that include Clostridium botulinum,
C. difficile, C. perfringens, C. tetani, Escherichia coli, Helicobacter pylori, and
Listeriamonocytogenes.
This current handbook, consisting of 24 chapters, is a major reference work on
microbialtoxinswrittenbyapanelofinternationalexperts.
ix
Contents
PartI BacillusToxins ...................................... 1
1 BacillusanthracisToxins:EfficientBiochemicalWeaponsfor
theInfectiousBattle .................................... 3
YannickTrescos,ClémenceRougeaux,andJean-NicolasTournier
2 ModeofActionofCryToxinsfromBacillusthuringiensisand
ResistanceMechanisms .................................. 15
MarioSoberón,RoseMonnerat,andAlejandraBravo
PartII BurkholderiaToxins ................................. 29
3 BurkholderiapseudomalleiToxinsandClinicalImplications ..... 31
PerumalSamyRamar,GautamSethi,BradleyG.Stiles,SokLinFoo,
OctavioLuizFranco,ArfusoF.,LinaH.K.Lim,and
P.Gopalakrishnakone
PartIII ClostridiumToxins .................................. 51
4 ClostridiumperfringensEpsilonToxin:Structuraland
MechanisticInsights .................................... 53
MichelR.Popoff,BradleyStiles,andBernardPoulain
5 ClostridiumperfringensIotaToxin:ASuccessfullySharedTemplate
forCommonEntericPathogens ........................... 73
BradleyG.Stiles,HolgerBarth,andMichelR.Popoff
6 RoleofClostridiumperfringensAlpha,Beta,Epsilon,andIota
ToxinsinEnterotoxemiaofMonogastricsandRuminants ....... 93
MarianoE.Fernandez-MiyakawaandLeandroM.Redondo
7 RoleofClostridiumperfringensToxinsinNecroticEnteritisin
Poultry ............................................... 119
M.Flores-Díaz,E.Barquero-Calvo,M.Ramírez,andA.Alape-Girón
xi
xii Contents
8 StructureFunctionStudiesofLargeClostridialCytotoxins ..... 135
JosephW.AlvinandD.BordenLacy
9 RoleofClostridiumdifficileToxinsinAntibiotic-Associated
DiarrheaandPseudomembranousColitis ................... 153
DianaLópez-Ureña,CarlosQuesada-Gómez,CésarRodríguez,and
EstebanChaves-Olarte
10 TetanusandBotulinumNeurotoxins ....................... 171
OrnellaRossettoandCesareMontecucco
PartIV EscherichiaToxins ................................. 187
11 EscherichiacoliShigaToxin .............................. 189
SamuelM.ChekababandJoséeHarel
12 EscherichiacoliSTbEnterotoxin:AMultifacetedMolecule ..... 205
J.DanielDubreuil
13 Structure,Enterotoxicity,andImmunogenicityof
EnterotoxigenicEscherichiacoliHeat-StableTypeIToxin(STa)
andDerivatives ........................................ 223
QiangdeDuanandWeipingZhang
PartV HelicobacterToxins ................................ 245
14 HelicobacterpyloriCagA:TheBacterialOncoprotein .......... 247
PaoloRuggiero
15 InteractionofHelicobacterpyloriVacAToxinwithItsTarget
Cells ................................................. 267
VittorioRicciandPatriziaSommi
PartVI ListeriaToxins .................................... 295
16 RoleofListeriamonocytogenesExotoxinsinVirulence ......... 297
JuanJoséQuereda,PascaleCossart,andJavierPizarro-Cerdá
17 BacterialPore-FormingToxininMacromoleculeDelivery:
LessonsLearnedfromListeriolysinO ...................... 317
ManasMandal
PartVII GeneralMechanismsofToxinAction ................ 329
18 ChaperonesandADP-RibosylatingBacterialToxins ........... 331
HolgerBarthandKatharinaErnst
