Advances in Biochemical Engineering/Biotechnology 135 Series Editor: T. Scheper Andreas Vilcinskas Editor Yellow Biotechnology I Insect Biotechnologie in Drug Discovery and Preclinical Research 135 Advances in Biochemical Engineering/Biotechnology Series editor T. Scheper, Hannover, Germany Editorial Board S. Belkin, Jerusalem, Israel P. M. Doran, Hawthorn, Australia I. Endo, Saitama, Japan M. B. Gu, Seoul, Korea W.-S. Hu, Minneapolis, MN, USA B. Mattiasson, Lund, Sweden J. Nielsen, Göteborg, Sweden G. Stephanopoulos, Cambridge, MA, USA R. Ulber, Kaiserslautern, Germany A.-P. Zeng, Hamburg-Harburg, Germany J.-J. Zhong, Shanghai, China W. Zhou, Framingham, MA, USA For furthervolumes: http://www.springer.com/series/10 Aims and Scope Thisbookseriesreviewscurrenttrendsinmodernbiotechnologyandbiochemical engineering. Its aim is to cover all aspects of these interdisciplinary disciplines, where knowledge, methods and expertise are required from chemistry, biochem- istry, microbiology, molecular biology, chemical engineering and computer science. Volumes are organized topically and provide a comprehensive discussion of developments in the field over the past 3–5 years. The series also discusses new discoveries and applications. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their syn- thesis and purification. Ingeneral, volumes are edited by well-knownguest editors. Theseries editor and publisher will, however, always be pleased to receive suggestions and supple- mentary information. Manuscripts are accepted in English. Inreferences,AdvancesinBiochemicalEngineering/Biotechnologyisabbreviated as Adv. Biochem. Engin./Biotechnol. and cited as a journal. Andreas Vilcinskas Editor Yellow Biotechnology I Insect Biotechnologie in Drug Discovery and Preclinical Research With contributions by Iris V. Adam (cid:2) Yiorgos Apidianakis (cid:2) Ludmila Bauer Katja Becker (cid:2) Helge B. Bode (cid:2) Michael Boll Alexander O. Brachmann (cid:2) Annely Brandt Theodoulakis Christofi (cid:2) Christine Fink (cid:2) Rainer Fischer Stefanie Grünwald (cid:2) Ana-Maria Gurmai Julia Hoffmann (cid:2) Yuan-Ying Jiang (cid:2) De-Dong Li Franziska Mohring (cid:2) Krishnendu Mukherjee Eleftherios Mylonakis (cid:2) Jette Pretzel (cid:2) Stefan Rahlfs Ramya Raju (cid:2) Thomas Roeder (cid:2) Renja Romey Andreas Vilcinskas (cid:2) Yan Wang (cid:2) Uwe Wenzel 123 Editor Andreas Vilcinskas Bioresources ProjectGroup Fraunhofer InstituteforMolecular Biology Giessen Germany ISSN 0724-6145 ISSN 1616-8542 (electronic) ISBN 978-3-642-39862-9 ISBN 978-3-642-39863-6 (eBook) DOI 10.1007/978-3-642-39863-6 SpringerHeidelbergNewYorkDordrechtLondon LibraryofCongressControlNumber:2013948660 (cid:2)Springer-VerlagBerlinHeidelberg2013 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. 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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. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface Yellow Biotechnology has been introduced as a synonymous term for insect bio- technology, which can be defined as the use of biotechnology-based methods for the development of insects (or their molecules, cells, organs or associated microorganisms) into products and services for specific applications in medicine, plant protection or industry. This emerging field has an enormous economic potential and the remarkable promise of the Yellow Biotechnology value chain is attracting increasing interest and investment, particularly from the growing Asian economiesofChina,JapanandSouthKorea.In2010,thegrowthofthisemerging field inspired Springer to publish the first book dedicated to this subject, entitled Insect Biotechnology (edited by Prof. Andreas Vilcinskas), which has now been translated into a number of languages. Therapiddevelopmentofinsectbiotechnologyandtheexpandingapplications of insect-derived models and tools have motivated both Springer and the editor Andreas Vilcinskas to publish two further volumes on Yellow Biotechnology within the Springer book series Advances in Biochemical Engineering and Bio- technology, to complement the original publication. Yellow Biotechnology Part I focuses on the use of insects in drug discovery and preclinical research, whereas YellowBiotechnologyPartIIconsiderstheapplicationsofinsectbiotechnologyin plant protection and industry. Insects can be used as sources of new drugs, particularly antibiotics, but their medical use extends well beyond insects as bioresources, and now includes their development as powerful preclinical research models, facilitating both the inves- tigationofmolecularmechanismsunderlyinghumandiseasesandtheinexpensive and ethical in vivo testing of drugs in suitable whole-animal-high-throughput systems.YellowBiotechnologyPartIcomprisessixchaptersaddressingtheuseof insect models for the analysis of human diseases, preclinical research and food safety, and is the largest collection of chapters on this subject. The transferability of data representing molecular mechanisms from insect models to humans has profited from the availability of insects with completely-sequenced genomes and rapidprogressingenome-scalebioinformatics.Twofurtherchaptershighlightthe use of insects in drug discovery. Insects are taxonomically diverse and therefore offer the opportunity to source thousands of new molecular entities with phar- macological properties. In contrast, pest insects are major competitors for human food/animal feed, and vector insects transmit diseases such as plague and malaria v vi Preface thathavethreatenedhumansanddomesticanimalsthroughouthistoryandstillkill millions of people every year. Yellow Biotechnology therefore considers bio- technology-basedstrategiestodevelopsustainablemethodstocontrolinsectpests and vectors. The majority of authors contributing to Yellow Biotechnology are members of the first German collaborative Insect Biotechnology research group, which is funded by the Hessen State Ministry of Higher Education, Research and the Arts via the excellence program LOEWE. This research program is hosted by the Justus-Liebig-University of Giessen and coordinated by the Editor Andreas Vilcinskas. In collaboration with the Fraunhofer Institute of Molecular Biology andAppliedEcology,it represents thefirst operational unitinGermany thataims to explore insects as a source of new compounds for specific applications in medicine, plant protection and industry. The Hessian research focus on Insect Biotechnologyincludesfundingfor25Ph.D.students,someofwhomcontributed chapters to this publication. We are aware that even two volumes are not sufficient to provide exhaustive coverage of this burgeoning research and development field, butwe hope that the collectedchapterswillprovideanoverviewofthediverseandexpandingfrontiers of Yellow Biotechnology. Summer 2013 Andreas Vilcinskas Contents Utility of Insects for Studying Human Pathogens and Evaluating New Antimicrobial Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Yan Wang, De-Dong Li, Yuan-Ying Jiang and Eleftherios Mylonakis Galleria Mellonella as a Model Host to Study Gut Microbe Homeostasis and Brain Infection by the Human Pathogen Listeria Monocytogenes. . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Krishnendu Mukherjee, Ramya Raju, Rainer Fischer and Andreas Vilcinskas Drosophila as a Model to Study Metabolic Disorders . . . . . . . . . . . . . 41 Julia Hoffmann, Renja Romey, Christine Fink and Thomas Roeder The Fruit Fly Drosophila melanogaster as a Model for Aging Research. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Annely Brandt and Andreas Vilcinskas Drosophila and the Hallmarks of Cancer . . . . . . . . . . . . . . . . . . . . . . 79 Theodoulakis Christofi and Yiorgos Apidianakis The Red Flour Beetle Tribolium castaneum as a Model to Monitor Food Safety and Functionality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 Stefanie Grünwald, Iris V. Adam, Ana-Maria Gurmai, Ludmila Bauer, Michael Boll and Uwe Wenzel Identification and Bioanalysis of Natural Products from Insect Symbionts and Pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Alexander O. Brachmann and Helge B. Bode Antiparasitic Peptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Jette Pretzel, Franziska Mohring, Stefan Rahlfs and Katja Becker Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 vii AdvBiochemEngBiotechnol(2013)135:1–25 DOI:10.1007/10_2013_194 (cid:2)Springer-VerlagBerlinHeidelberg2013 PublishedOnline:19April2013 Utility of Insects for Studying Human Pathogens and Evaluating New Antimicrobial Agents Yan Wang, De-Dong Li, Yuan-Ying Jiang and Eleftherios Mylonakis Abstract Insectmodels,suchasGalleriamellonellaandDrosophilamelanogaster have significant ethical, logistical, and economic advantages over mammalian modelsforthestudiesofinfectiousdiseases.Usingthesemodels,variouspathogenic microbeshavebeenstudiedandmanynovelvirulencegeneshavebeenidentified. Notably,becauseinsectsaresusceptibletoawidevarietyofhumanpathogensand haveimmuneresponsessimilartothoseofmammals,theyoffertheopportunityto understandinnateimmuneresponsesagainsthumanpathogensbetter.Itisimportant tonotethatinsectpathosystemshavealsoofferedasimplestrategytoevaluatethe efficacyandtoxicityofmanyantimicrobialagents.Overall,insectmodelsprovidea rapid, inexpensive, and reliable way as complementary hosts toconventional ver- tebrateanimalmodelstostudypathogenesisandantimicrobialagents. Keywords Antimicrobial efficacy (cid:2) Drosophila (cid:2) Galleria (cid:2) Infection (cid:2) Insect (cid:2) Pathogen (cid:2) Pathogenesis Abbreviations MRSA Methicillin-resistant Staphylococcus aureus RNAi RNA interference Y.Wang(cid:2)D.-D.Li(cid:2)Y.-Y.Jiang NewDrugResearchandDevelopmentCenter,SchoolofPharmacy, SecondMilitaryMedicalUniversity,Shanghai200433,China Y.Wang(&)(cid:2)E.Mylonakis(&) DivisionofInfectiousDiseases,MassachusettsGeneralHospital, HarvardMedicalSchool,BostonMA,02114,USA e-mail:[email protected] E.Mylonakis e-mail:[email protected] E.Mylonakis DivisionofInfectiousDiseases,RhodeIslandHospital,WarrenAlpertMedical SchoolofBrownUniversity,RhodeIsland02903,USA 2 Y.Wangetal. Contents 1 Introduction.......................................................................................................................... 2 2 UseofInsectsforStudyingHumanPathogens................................................................. 3 2.1 GalleriamellonellaInfectionModel.......................................................................... 3 2.2 DrosophilamelanogasterInfectionModel................................................................. 5 2.3 OtherInsectInfectionModels.................................................................................... 7 3 UseofInsectsforEvaluatingNewAntimicrobialAgents................................................ 8 3.1 GalleriamellonellaInfectionModelforEvaluatingNewAntimicrobialAgents.... 8 3.2 DrosophilamelanogasterInfectionModelforEvaluatingNew AntimicrobialAgents.................................................................................................. 12 3.3 OtherInsectInfectionModelsforEvaluatingNewAntimicrobialAgents............. 12 4 Conclusion........................................................................................................................... 13 References.................................................................................................................................. 13 1 Introduction Pathogenicmicrobescauseavarietyofinfectiousdiseasesinhumanhosts,andthe threatfromthesepathogenshasneverfadedinhumanhistory[1–6].Forexample, methicillin-resistant Staphylococcus aureus (MRSA) alone infects more than 94,000peopleandkillsnearly19,000intheUnitedStateseveryyear,moredeaths than those caused by HIV/AIDS, Parkinson’s disease, emphysema, and homicide combined[7,8].Also,inadditiontobacterialinfections,thefrequency,spectrum, and associated cost of opportunistic invasive fungal infections have significantly increased over the past two decades and accounted for the rapidly growing pop- ulations of immunosuppressed and debilitated patients [9–11]. The substantial disease burden of infectious diseases in humans underscores the need for better understanding of the pathogenicity and virulence of human pathogens. Pathogenesis, immunology, and pharmacology research have traditionally reliedonmammalianmodelssuchasmice,rats,rabbits,andguineapigs,butsuch experiments are costly, time consuming, and require full ethical consideration. Hence,cheaperandethicallymoreacceptableinsectmodelsofinfectionhavebeen introduced, including the larvae of the greater wax moth Galleria mellonella, Drosophila melanogaster, and other insects. Accumulating data indicate that the virulence of many human pathogens is comparable in insects and mammals, and often identical virulencefactors are used byhumanpathogenic microbes to infect insects and mammals. Moreover, insects have an immune system that is func- tionally similar to the innate immune system of mammals, which offers a simple model to understand innate immunity better. Furthermore, the insect infection models provide a rapid, inexpensive, and reliable evaluation of the efficacy and toxicity of new antimicrobial agents in vivo. In this chapter, we discuss how the insectsG.mellonella,D.melanogaster,andotherinsectscanbeemployedtostudy various human pathogens and to evaluate new antimicrobial agents.
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