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Current Topics in Microbiology and Immunology Gad Frankel · Eliora Z. Ron Editors Escherichia coli, a Versatile Pathogen Current Topics in Microbiology and Immunology Volume 416 Series editors RafiAhmed SchoolofMedicine,RollinsResearchCenter,EmoryUniversity,RoomG211,1510Clifton Road,Atlanta, GA30322,USA ShizuoAkira Immunology Frontier Research Center, OsakaUniversity, 3-1 Yamadaoka, Suita,Osaka 565-0871, Japan KlausAktories Medizinische Fakultät, Institut für Experimentelle undKlinische Pharmakologie und Toxikologie, Abt. I,Albert-Ludwigs-Universität Freiburg, Albertstr.2579104, Freiburg, Germany ArturoCasadevall W.HarryFeinstoneDepartmentofMolecularMicrobiology&Immunology,JohnsHopkins BloombergSchool ofPublic Health, 615N.Wolfe Street, RoomE5132,Baltimore MD 21205, USA Richard W.Compans DepartmentofMicrobiologyandImmunology,EmoryUniversity,1518CliftonRoad,CNR 5005, Atlanta GA30322,USA Jorge E. Galan BoyerCtr. for Molecular Medicine, Schoolof Medicine,Yale University,295Congress Avenue,room 343, NewHaven,CT 06536-0812,USA AdolfoGarcia-Sastre IcahnSchoolofMedicineatMountSinai,DepartmentofMicrobiology,1468MadisonAve., Box1124, NewYork,NY10029, USA AkikoIwasaki Department ofImmunobiology, TACS655, YaleUniversity Schoolof Medicine, PO Box208011, NewHaven,CT 06520-8011,USA Bernard Malissen Centred’ImmunologiedeMarseille-Luminy,ParcScientifiquedeLuminy,Case906,13288, Marseille Cedex9, France KlausPalme Institute of Biology II/Molecular Plant Physiology, Albert-Ludwigs-Universität Freiburg, Freiburg, 79104,Germany RinoRappuoli GSKVaccines, ViaFiorentina 1, Siena53100,Italy More information about this series at http://www.springer.com/series/82 Gad Frankel Eliora Z. Ron (cid:129) Editors Escherichia coli, a Versatile Pathogen Responsible series editor: Rino Rappuoli 123 Editors Gad Frankel Eliora Z. Ron Department ofLife Sciences Faculty of LifeSciences Imperial CollegeLondon TelAviv University London,UK TelAviv, Israel ISSN 0070-217X ISSN 2196-9965 (electronic) CurrentTopics inMicrobiology andImmunology ISBN978-3-319-99663-9 ISBN978-3-319-99664-6 (eBook) https://doi.org/10.1007/978-3-319-99664-6 LibraryofCongressControlNumber:2018961004 ©SpringerNatureSwitzerlandAG2018 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpart of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission orinformationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodologynowknownorhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfrom therelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontainedhereinor for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations. ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Foreword The species Escherichia coli represents well-known microorganisms that are used as “working horses” in molecular biology, genomics, and biotechnology. It has long been recognized that Escherichia coli is also a group of organisms with high pathogenic potential both intestinally and extraintestinally. In addition, E. coli is a member of the microbiome in humans, animals, and even plants. In summary, E. coli is an organism with countless faces and the present book addresses various aspects of this organism. Bacteria of Shigella species are strongly related to E. coli, so one could claim that Shigella organisms belong to the E. coli species. In the first chapter, Ilia Belotserkovsky and Philippe Sansonetti describe the cell biology of E. coli like Shigella pathogens causing infections of the gut. Claire Jenkins describes enteroaggregative E. coli bacteria, which have thecapacity tocolonize thegut and to induce gut-associated infectious diseases. Her findings are presented in the second chapter. ShigellaandanumberofE.colipathogenspossessgeneclustersencodingfora TypeIIIsecretionsystem(T3SS).Inhischapter,GadFrankeldescribestheTypeIII system machinery of EPEC, which enables the transport of proteins from microorganisms. The Type III secretion machineries allow the transfer of effector molecules to the outside and into intestinal host cells. Intestinal pathogenic E. coli uses this mechanism to stimulate diseases. The chapter of Abigail Clements describes the roles of the infected E. coli effectors, while the chapter written by Helge Karch deals with enterohemorrhagic E. coli (EHEC), which play an important role in public health issues. EHEC bacteria are able to induce gut-associatedinfections.Furthermore,theShigatoxins—producedbyEHEC—are responsible for diseases outside the gut, e.g., the kidney. Inadditiontointestinalinfections,E.colistrainsmayalsoinduceextraintestinal diseases, such as infections of the urinary tract and systemic infections. Eliora Ron’s chapter introduces the various types of extraintestinal pathogens containing the capacity to induce diseases in humans and animals. The analysis of these pathogensunderthe“OneHealth”aspectisofutmostimportance,sinceE.coliisa v vi Foreword “melting pot” for gene transfer both among various strains of E. coli as well as of other bacterial species. Uri Gophna, an expert in genetic analysis of E. coli, describes in his chapter evolutionary processes and the emerging drug resistance in E. coli—another important topic in the biology of this microorganism. Next to its role as intestinal and extraintestinal pathogens, E. coli act is also a commensal bacterium in the gut of many species. Various sequence types of E. coli play a role in drug resistance, gene transfer, and pathogenicity. Joseph Paitan illustrates these aspects in his chapter. Asmentioned,E.colistrainsareseriouspathogens.Therefore,itisnecessaryto developvaccinesinorder tocombatintestinal andextraintestinalinfections.Inher chapter,MariagraziaPizzadescribestheseeffortsundertakeninthedevelopmentof vaccines against different types of E. coli. Summarizing thearticles published inthis bookonE.coli,,itisclear thatthese highlydiverseorganismsplayanimportantroleinmanyareasfrompublichealthto biotechnologyandotherfields.Istronglyrecommendthisbookforfurtherreading and discussions. Halle, Germany Jörg Hacker President of the German Academy of Sciences Leopoldina—National Academy of Sciences Contents Shigella and Enteroinvasive Escherichia Coli . . . . . . . . . . . . . . . . . . . . . 1 Ilia Belotserkovsky and Philippe J. Sansonetti Enteroaggregative Escherichia coli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Claire Jenkins The Type III Secretion System of Pathogenic Escherichia coli. . . . . . . . 51 Sabrina L. Slater, Agnes M. Sågfors, Dominic J. Pollard, David Ruano-Gallego and Gad Frankel Modulation of Host Cell Processes by T3SS Effectors . . . . . . . . . . . . . . 73 Avinash R. Shenoy, R. Christopher D. Furniss, Philippa J. Goddard and Abigail Clements The 2011 German Enterohemorrhagic Escherichia Coli O104:H4 Outbreak—The Danger Is Still Out There . . . . . . . . . . . . . . . 117 Stefanie Kampmeier, Michael Berger, Alexander Mellmann, Helge Karch and Petya Berger Extraintestinal Pathogenic Escherichia coli . . . . . . . . . . . . . . . . . . . . . . 149 Dvora Biran and Eliora Z. Ron Pandemic Bacteremic Escherichia Coli Strains: Evolution and Emergence of Drug-Resistant Pathogens. . . . . . . . . . . . . . . . . . . . . 163 Yael Yair and Uri Gophna Current Trends in Antimicrobial Resistance of Escherichia coli . . . . . . 181 Yossi Paitan Vaccines Against Escherichia coli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 Barbara Nesta and Mariagrazia Pizza vii Shigella and Enteroinvasive Escherichia Coli Ilia Belotserkovsky and Philippe J. Sansonetti Contents 1 Introduction.......................................................................................................................... 2 2 EvolutionofEnteroinvasivePathovarsofE.Coli............................................................. 3 3 ColonizationoftheIntestinalLumenandPreparationoftheVirulenceArsenal............. 5 4 SubversionofIntestinalEpithelialCells............................................................................. 6 4.1 Diarrhea-InducingToxins........................................................................................... 6 4.2 InvasiontotheColonicEpithelium........................................................................... 7 4.3 IntracellularMovement,AutophagyEscape,andDissemination.............................. 11 4.4 EpithelialIntegrityPreservation................................................................................. 12 5 SubversionoftheImmuneSystem..................................................................................... 13 5.1 ManipulationoftheHostInnateImmunity............................................................... 13 5.2 ManipulationoftheHostAdaptiveImmunity.......................................................... 16 6 ConcludingRemarks........................................................................................................... 17 References.................................................................................................................................. 19 Abstract Shigella and enteroinvasive Escherichia coli (EIEC) are gram-negative bacteria responsible for bacillary dysentery (shigellosis) in humans, which is characterized by invasion and inflammatory destruction of the human colonic epithelium. Different EIEC and Shigella subgroups rose independently from com- mensal E. coli through patho-adaptive evolution that included loss of functional genes interfering with the virulence and/or with the intracellular lifestyle of the bacteria, as well as acquisition of genetic elements harboring virulence genes. Among the latter isthe large virulenceplasmid encoding for a type three secretion system (T3SS), which enables translocation of virulence proteins (effectors) from I.Belotserkovsky(&) UnitédePathogénieMicrobienneMoléculaire,InstitutPasteur, 28RueDuDrRoux,75724Cedex15Paris,France e-mail:[email protected] P.J.Sansonetti MicrobiologieetMaladiesInfectieuses,CollègedeFrance, 11PlaceMarcelinBerthelot,75005Paris,France e-mail:[email protected] CurrentTopicsinMicrobiologyandImmunology(2018)416:1–26 DOI10.1007/82_2018_104 ©SpringerInternationalPublishingAG,partofSpringerNature2018 PublishedOnline:15September2018 2 I.BelotserkovskyandP.J.Sansonetti the bacterium directly into the host cell cytoplasm. These effectors enable the pathogentosubvertepithelial cell functions, promotingits own uptake,replication in the host cytosol, and dissemination to adjacent cells while concomitantly inhibiting pro-inflammatory cell death. Furthermore, T3SS effectors are directly involved in Shigella manipulation of immune cells causing their dysfunction and promoting cell death. In the current chapter, we first describe the evolution of the enteroinvasivepathovarsandthensummarizetheoverallknowledgeconcerningthe pathogenesis of these bacteria, with a particular focus on Shigella flexneri. Subversion of host cell functions in the human gut, both epithelial and immune cells, by different virulence factors is especially highlighted. 1 Introduction Bacillarydysentery(orshigellosis)isclinicallycharacterizedbyseverebloodyand mucous diarrhea associated with fever and abdominal cramps. These symptoms reflect invasion of bacteria into colonic and rectal mucosa, provoking a strong inflammatory response that leads to destruction of the colonic epithelium. Life-threatening complications may also occur including hypoglycemia, bac- teremia, septicemia, hemolytic uremic syndrome leading to acute renal failure and toxic megacolon (a lower intestinal occlusion accompanied by perforation and peritonitis) (van den Broek et al. 2005). Unlike other enteric infections (i.e., rota- virus, enterotoxigenic E. coli (ETEC), and Vibrio cholerae) that are marked by severe watery diarrhea, shigellosis is less likely to induce major purge; hence, dehydrationandelectrolyteimbalancearelessfrequent.Shigellosisremainsoneof the leading causes of morbidity and mortality mostly in low-income countries especially among children under 5 years old in endemic regions (Kotloff et al. 2013). In addition, bacillary dysentery contributes to malnutrition causing severe growth retardation in young children (van den Broek et al. 2005). The etiological agents of shigellosis are E. coli-related bacteria which, histori- cally, were divided into Shigella species (with four subgroups) and enteroinvasive Escherichia coli (EIEC) species, depending on several clinical and biochemical differences. However, with the development of molecular tools and the rise of the genomicsera,itbecameclearthatthesespeciesbelongtothesamegenusaswellas other pathogenic and commensal E. coli (discussed below). The unique feature of dysentery-causing strains is theability to invade host cells,which requires specific molecular adaptations from the bacterial side and induces a particular immune response from the host side. In the current chapter, we first briefly describe the evolution of enteroinvasive E. coli subgroups and then focus on the virulence factors that enable these bacteria to invade and colonize the intestinal mucosa through manipulation of both epithelium and immune system. Since Shigella flexneri is the most studied subgroup, it is used as an example throughout this review while other subgroup specific factors are occasionally discussed.

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