Ricin and Shiga Toxins: Pathogenesis, Immunity, Vaccines and Therapeutics

283 Pages·2012·3.921 MB·English

by  Nilgun E. Tumer, Xiao-Ping Li (auth.), Nicholas Mantis (eds.)

Current Topics in Microbiology and Immunology
Volume 357
Series Editors
Klaus Aktories
Medizinische Fakultät, Institut für Experimentelle und Klinische Pharmakologie
und Toxikologie, Albert-Ludwigs-Universität Freiburg, Abt. I, Albertstr. 25,
79104 Freiburg, Germany
Richard W. Compans
Influenza Pathogenesis and Immunology Research Center, Emory University,
School of Medicine, Atlanta, GA 30322, USA
Max D. Cooper
Department of Pathology and Laboratory Medicine, Georgia Research Alliance,
Emory University, 1462 Clifton Road, Atlanta, GA 30322, USA
Yuri Y. Gleba
ICON Genetics AG, Biozentrum Halle, Weinbergweg 22, 06120 Halle, Germany
Tasuku Honjo
DepartmentofMedicalChemistry,FacultyofMedicine,KyotoUniversity,Sakyo-ku,
Yoshida,Kyoto,606-8501,Japan
Hilary Koprowski
Biotechnology Foundation, Inc., 119 Sibley Avenue, Ardmore, PA 19003, USA
Bernard Malissen
Centre d’Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case
906, 13288, Marseille Cedex 9, 13288, France
Fritz Melchers
MaxPlanckInstituteforInfectionBiology,Charitéplatz1,10117Berlin,Germany
Michael B. A. Oldstone
Department of Neuropharmacology, Division of Virology, The Scripps Research
Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Peter K. Vogt
Department of Molecular and Experimental Medicine, The Scripps Research
Institute, 10550 North Torrey Pines Road, BCC-239, La Jolla, CA 92037, USA
Current Topics in Microbiology and Immunology
Previously publishedvolumes
Further volumes canbe foundatwww.springer.com
Vol.329:Griffin,DianeE.; Vol.342:Arvin,AnnM.(Ed.):
Oldstone,MichaelB.A.(Eds.):Measles.2009 Varicella-zosterVirus.2010.
ISBN978-3-540-70522-2 ISBN978-3-642-12727-4
Vol.330:Griffin,DianeE.; Vol.343:Johnson,JohnE.(Ed.):
Oldstone,MichaelB.A.(Eds.): CellEntrybyNon-EnvelopedViruses.2010.
Measles.2009. ISBN978-3-642-13331-2
ISBN978-3-540-70616-8
Vol.344:Dranoff,Glenn(Ed.):
Vol.331:Villiers,E.M.de(Ed.): CancerImmunologyandImmunotherapy.2011.
TTViruses.2009. ISBN978-3-642-14135-5
ISBN978-3-540-70917-8
Vol.345:Simon,M.Celeste(Ed.):
Vol.332:KarasevA.(Ed.): DiverseEffectsofHypoxiaonTumorProgression.2010.
PlantproducedMicrobialVaccines.2009. ISBN978-3-642-13328-2
ISBN978-3-540-70857-5
Vol.346:ChristianRommel;BartVanhaesebroeck;
Vol.333:Compans,RichardW.; PeterK.Vogt(Ed.):
Orenstein,WalterA.(Eds.): Phosphoinositide3-kinaseinHealthandDisease.2010.
VaccinesforPandemicInfluenza.2009. ISBN978-3-642-13662-7
ISBN978-3-540-92164-6
Vol.347:ChristianRommel;BartVanhaesebroeck;
Vol.334:McGavern,Dorian;Dustin,Micheal(Eds.): PeterK.Vogt(Ed.):
VisualizingImmunity.2009. Phosphoinositide3-kinaseinHealthandDisease.2010.
ISBN978-3-540-93862-0 ISBN978-3-642-14815-6
Vol.335:Levine,Beth;Yoshimori,Tamotsu; Vol.348:LyubomirVassilev;DavidFry(Eds.):
Deretic,Vojo(Eds.): Small-MoleculeInhibitorsofProtein-Protein
AutophagyinInfectionandImmunity.2009. Interactions.2011.
ISBN978-3-642-00301-1 ISBN978-3-642-17082-9
Vol.349:MichaelKartin(Ed.):
Vol.336:Kielian,Tammy(Ed.): NF-kBinHealthandDisease.2011.
Toll-likeReceptors:RolesinInfectionand ISBN:978-3-642-16017-2
Neuropathology.2009.
ISBN978-3-642-00548-0 Vol.350:RafiAhmed;TasukuHonjo(Eds.):
NegativeCo-receptorsandLigands.2011.
Vol.337:Sasakawa,Chihiro(Ed.):
ISBN:978-3-642-19545-7
MolecularMechanismsofBacterialInfectionviatheGut.
2009. Vol.351:Marcel,B.M.Teunissen(Ed.):
ISBN978-3-642-01845-9 IntradermalImmunization.2011.
ISBN:978-3-642-23689-1
Vol.338:Rothman,AlanL.(Ed.):
DengueVirus.2009. Vol.352:RudolfValenta;RobertL.Coffman(Eds.):
ISBN978-3-642-02214-2 VaccinesagainstAllergies.2011.
ISBN978-3-642-20054-0
Vol.339:Spearman,Paul;Freed,EricO.(Eds.):
HIVInteractionswithHostCellProteins.2009. Vol.353:CharlesE.Samuel(Ed.):
ISBN978-3-642-02174-9 AdenosineDeaminasesActingonRNA(ADARs)
andA-to-IEditing.2011.
Vol.340:Saito,Takashi;Batista,FacundoD.(Eds.):
ISBN978-3-642-22800-1
ImmunologicalSynapse.2010.
ISBN978-3-642-03857-0 Vol.354:PamelaA.Kozlowski(Ed.):
MucosalVaccines.2012.
Vol.341:Bruserud,Øystein(Ed.):
ISBN978-3-642-23692-1
TheChemokineSysteminClinical
andExperimentalHematology.2010.
ISBN978-3-642-12638-3
Nicholas J. Mantis
Editor
Ricin and Shiga Toxins
Pathogenesis, Immunity, Vaccines
and Therapeutics
Responsible series editor: Klaus Aktories
123
Nicholas J.Mantis
Division ofInfectious Diseases
WadsworthCenter
New YorkState Department ofHealth
120New Scotland Ave
Albany,NY12208
USA
ISSN 0070-217X
ISBN 978-3-642-27469-5 e-ISBN978-3-642-27470-1
DOI 10.1007/978-3-642-27470-1
SpringerHeidelbergNewYorkDordrechtLondon
LibraryofCongressControlNumber:2011945111
(cid:2)Springer-VerlagBerlinHeidelberg2012
Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor
informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar
methodology now known or hereafter developed. Exempted from this legal reservation are brief
excerpts in connection with reviews or scholarly analysis or material supplied specifically for the
purposeofbeingenteredandexecutedonacomputersystem,forexclusiveusebythepurchaserof
thework.Duplicationofthispublicationorpartsthereofispermittedonlyundertheprovisionsofthe
CopyrightLawofthePublisher’slocation,initscurrentversion,andpermissionforusemustalwaysbe
obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright
ClearanceCenter.ViolationsareliabletoprosecutionundertherespectiveCopyrightLaw.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt
fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
While the advice and information in this book are believed to be true and accurate at the date of
publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor
anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with
respecttothematerialcontainedherein.
Coverdesign:Deblik,Berlin
Printedonacid-freepaper
SpringerispartofSpringerScience+BusinessMedia(www.springer.com)
Preface
At first glance, a volume dedicated to two seemingly very different toxins, ricin
andShiga,mayseempuzzling.Ricintoxinisaby-productofcastorbeans,which
are cultivated and processed on an industrial scale throughout the world for their
oils. Shiga toxins (Stx), on the other hand, are produced by enteric bacterial
pathogens, namely Shigella dysenteriae serotype 1 and certain strains of Esche-
richia coli, which collectively are responsible for causing illness in thousands of
individuals each year. Ricin is a heterodimer, consisting of a single enzymatic
subunit and a single receptor-binding subunit, while Stx is comprised of a single
enzymatic subunit and five receptor-binding subunits. The two toxins show very
limited primary amino acid identity and have little to no demonstrable immune
cross-reactivity.
Uponcloserexamination,however,thetoxinsareremarkablysimilar.Ricinand
Stx are both ribosome-inactivating proteins (RIPs), by virtue of their ability to
depurinateahighlyconservedadenosineresiduewithinthesarcin-ricinloop(SRL)
of 28S ribosomal RNA. Structural analysis by X-ray crystallography, in con-
junction with mutagenesis studies, has revealed that the two toxins have identical
catalytic centers and enzymatic mechanisms. Although ricin and Stx use different
receptors to adhere to cell surfaces, the two toxins follow the same intracellular
retrogradetraffickingpathwaysfromthecellsurfacetotheendoplasmicreticulum
and beyond. Both toxins induce apoptosis of mammalian cells via complicated
signaling cascades involvingtheribotoxicstressresponse(RSR),aswellasstress
activated protein kinases (SAPK) pathways. Thus, ricin and Stx are more similar
than they are different.
The intent of this volume of Current Topics in Microbiology and Immunology
was to bring together a collection of in-depth and cutting edge reviews that
highlight our current understanding of the biology of ricin and Stx, with the long
term goal of advancing the development of countermeasures against these toxic
agents.InMayofthisyear,WesternEuropeexperiencedasevereoutbreakofStx-
producing E. coli (STEC) that culminated in more than 3,299 cases and over 40
deaths. While Stx is not the only virulence factor associated with STEC, it is
certainly the primary determinant associated with the onset of hemolytic uremic
v
vi Preface
syndrome(HUS).Atthepresenttime,therearenoclinicallyapprovedmeasuresto
neutralize Stx in individuals suffering from STEC infection. Nor are there any
preventatives or therapeutics for ricin toxin. Although incidents of ricin exposure
are largely unheard of, federal agencies and public health officials consider it a
significant threat. It is well documented that domestic and international terrorist
groups have stockpiled, and in some cases weaponized ricin with the intent of
releasing it into the public sphere and causing panic, illness and/or death on a
local, regional, or possibly national scale.
Asthetitleofthisvolumeindicates,thechapters,writtenbyleadingexpertsin
the field, are organized so as to cover all aspects of ricin and Stx, including
pathogenesis, immunity, vaccines and therapeutics. I would like to express my
sincereappreciationtoallmycolleagueswhotookgreatcareandeffortinputting
their chapters together andmakingthisvolume asuccess.Iam confident thatthis
outstandingcollectionofreviewswillserveasanimportantandreadilyaccessible
resource for the research community in the coming years.
Albany, NY, November 2011 Nicholas J. Mantis
Contents
Interaction of Ricin and Shiga Toxins with Ribosomes. . . . . . . . . . . . 1
Nilgun E. Tumer and Xiao-Ping Li
How Ricin and Shiga Toxin Reach the Cytosol of Target Cells:
Retrotranslocation from the Endoplasmic Reticulum . . . . . . . . . . . . . 19
Robert A. Spooner and J. Michael Lord
Ricin and Shiga Toxins: Effects on Host Cell Signal Transduction . . . 41
Dakshina M. Jandhyala, Cheleste M. Thorpe and Bruce Magun
Pathogenesis of Shiga-Toxin Producing Escherichia coli . . . . . . . . . . . 67
Angela Melton-Celsa, Krystle Mohawk, Louise Teel and Alison O’Brien
Shiga Toxin Pathogenesis: Kidney Complications
and Renal Failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Tom G. Obrig and Diana Karpman
The Induction of Apoptosis by Shiga Toxins and Ricin. . . . . . . . . . . . 137
Vernon L. Tesh
Small-Molecule Inhibitors of Ricin and Shiga Toxins . . . . . . . . . . . . . 179
Paul G. Wahome, Jon D. Robertus and Nicholas J. Mantis
Immunity to Ricin: Fundamental Insights into
Toxin–Antibody Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Joanne M. O’Hara, Anastasiya Yermakova and Nicholas J. Mantis
vii
viii Contents
Animal Models of Ricin Toxicosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Chad J. Roy, Kejing Song, Satheesh K. Sivasubramani,
Donald J. Gardner and Seth H. Pincus
Ricin Vaccine Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Joan E. Smallshaw and Ellen S. Vitetta
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Contributors
Donald J. GardnerNIAID Rocky Mountain Laboratories, Hamilton, MT 59840,
USA
Dakshina M. Jandhyala Tufts University School of Medicine, Tufts Medical
Center, 800 Washington Street, Box 041, Boston, MA 02111, USA, e-mail:
[email protected]
Diana Karpman Department of Pediatrics, Clinical Sciences Lund, Lund Uni-
versity, Lund, Sweden, e-mail: [email protected]
Xiao-Ping Li Department of Plant Biology and Pathology, School of Environ-
mental and Biological Sciences, Rutgers University, 59 Dudley Road, New
Brunswick, NJ 08901-8520, USA
J.MichaelLordSchoolofLifeSciences,UniversityofWarwick,Coventry,CV4
7AL, UK, e-mail: [email protected]
Bruce Magun Department of Cell and Developmental Biology, Oregon Health
and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239,
USA, e-mail: [email protected]
NicholasJ.MantisDivisionofInfectiousDisease,WadsworthCenter,NewYork
StateDepartmentofHealth,120NewScotlandAvenue,Albany,NY12208,USA;
DepartmentofBiomedicalSciences,UniversityatAlbanySchoolofPublicHealth,
Albany, NY 12201, USA, e-mail: [email protected]
Angela Melton-Celsa Department of Microbiology and Immunology, Uniformed
ServicesUniversityoftheHealthSciences,4301,JonesBridgeRd.,Bethesda,MD
20814, USA
Krystle Mohawk Department of Microbiology and Immunology, Uniformed
ServicesUniversityoftheHealthSciences,4301,JonesBridgeRd.,Bethesda,MD
20814, USA
ix