广西大学分子微生物学

分子微生物学从分子水平上研究微生物生命现象物质基础的学科。研究微生物细胞成分的物理、化学的性质和变化以及这些性质和变化与生命现象的关系，如遗传信息的传递，基因的结构、复制、转录、翻译、表达调控和表达产物的生理功能，以及细胞信号的转导等。《分子微生物学前沿》一书的内容聚焦在细菌分类、命名和鉴定领域的新进展；微生物抗不利环境的分子基础；微生物的基因水平转移与适应性进化；病原体相关分子模式与机体的模式识别；微生物群落与宿主相互作用；细菌的免疫系统、分泌系统、毒力系统、生物钟系统、生物波系统、纳管系统、膜囊泡系统等的构成及其意义；微生物菌群体感应系统和群体行为；病毒工厂和病毒与宿主相互作用的分子基础等方面。分子病毒学任课教师：温荣辉教授SARSCasesWorldwideReportedtoWHOasofJune6,2003China(5329)Singapore(206)HongKong(1750)Vietnam(63)Canada(219)U.S.(68)Europe:8countries(38)Thailand(8)Taiwan(676)Total:8404cases;779deaths(~10%casefatality)Australia&NZ(6)SA(2)Tenyearslater……Onehundredyearslater……2013.4.17Today……Chapter1Introductiontovirology病毒学简介Oncompletingthissession,youshouldbeableto:Understandwhatavirusis&explainhowvirusesdifferfromallotherorganisms.Summarizethehistoryofvirology&explainhowthepresentstateofourknowledgeofviruseswasachieved.Understandthecontentofmodernvirology.LearningObjectives:1.1TheHistoryofVirologyThefirstwrittenrecordofavirusinfectionisfromancientEgypt(3700BC),whichshowsatemplepriestwithtypicalsignsofparalyticpoliomyelitis.ThePharaohRaisesVdiedfromsmallpoxin1196BC&smallpoxwasendemicinChinaby1000BC.VirusisderivedfromtheGreekwordforpoisonandwasinitiallydescribedbyEdwardJennerin17981)Recognizingthatsurvivorsofsmallpoxoutbreakswereprotectedfromsubsequentinfection,theChineseinhaledthedriedcrustsfromsmallpoxlesionslikesnufforinoculatedthepusfromalesionintoascratchontheforearm-“variolation”.2)EdwardJennerwasnearlykilledbyvariolationattheageofseven!On14May1796,heusedcowpoxtosuccessfullyvaccinatean8-year-oldchild.Vaccinationagainstsmallpoxwasalmostuniversallyadoptedworldwideduringthenineteenthcentury.RobertKoch&LouisPasteurinthe1880sjointlyproposedthe'germtheory'ofdiseaseandthesignificanceoftheseorganismsbecameapparent.Koch’sPostulates1.Theagentmustbepresentineverycaseofthedisease.2.Theagentmustbeisolatedfromthehost&growninvitro.3.Thediseasemustbereproducedwhenapurecultureoftheagentisinoculatedintoahealthysusceptiblehost.4.Thesameagentmustberecoveredonceagainfromtheexperimentallyinfectedhost.1.1TheHistoryofVirologyRobertKoch(1843-1910)DimitriIwanowski(1892)showedthatextractsfromdiseasedtobaccoplantscouldtransmitdiseasetootherplantsafterpassagethroughceramicfiltersfineenoughtoretainthesmallestknownbacteria.Unfortunately,hedidnotrealizethefullsignificanceoftheseresults.ceramicfilterDimitriIwanowski(1864-1920)MartinusBeijerinick(1898)confirmed&extendedIwanowski'sresultsonTobaccomosaicvirus&wasthefirsttodevelopthemodernideaofthevirus,whichhereferredtoascontagiumvivumfluidum('solublelivinggerm').FreidrichLoeffler&PaulFrosch(1898)showedthatasimilaragentwasresponsibleforfoot-and-mouthdiseaseincattle.MartinusBeijerinick(1851-1931)FreidrichLoeffler(1852-1915)KarlLandsteiner&ErwinPopper(1909)showedthatpoliomyelitiswascausedbya'filterableagent'-thefirsthumandiseasetoberecognizedasbeingcausedbyavirus.KarlLandsteiner(1868-1945)poliomyelitis脊髓灰质炎FrederickTwort(1915)&Felixd'Herelle(1917)werethefirsttorecognizeviruseswhichinfectbacteria,whichd'Herellecalledbacteriophages(eatersofbacteria).Inthe1930s&subsequentdecades,pioneerssuchasSalvadorLuria,MaxDelbruck&manyothersusedthesevirusesasmodelsystemstoinvestigatemanyaspectsofvirology,includingvirusstructure,genetics,replication,etc.FrederickTwort(1877-1950)Theserelativelysimpleagentshavesincebeenveryimportanttoourunderstandingofalltypesofviruses,includingvirusesofhumanswhicharemuchmoredifficulttopropagate&study.Thehistoryofvirologyisthestoryofthedevelopmentofexperimentaltools&systemswithwhichvirusescouldbeexamined&bywhichwholenewareasofbiologywereopenedup.1.1TheHistoryofVirology.Virusesaresubmicroscopic,obligateintracellularparasitesVirusparticlesareproducedfromtheassemblyofpre-formedcomponents,whereasotheragentsgrowfromanincreaseintheintegratedsumoftheircomponents&reproducebydivisionVirusescontainnoenzymesofenergymetabolism,thuscannotmakeATP;Virusesdonotencodesufficientenzymaticmachinerytosynthesizetheircomponentmacromolecules,specifically,noproteinsynthesismachinery.VirusesaredistinctfromlivingorganismsVirusescanbeusefulVaccinedevelopmentGenetherapyToolstoinvestigatehostcells1.2whatisavirusVirusesmaybedefinedasobligateintracellularparasitesorganismsandvaryfrom20-200nminsize.Theyhavevariedshapeandchemicalcomposition,butcontainonlyDNAorRNA.Theintactparticleistermeda‘virion’whichconsistsofacapsidthatmaybeenvelopedfurtherbyaglycoprotein/lipidmembrane.Virusesareresistanttoantibiotics.Virusescannotbegrownonsterilemedia,butrequirethepresenceofspecifichostcells.Whatareviruses?“Apieceofbadnewswrappedupinaprotein”Whatareviruses?Nucleicacidgenome:DNAorRNAProteincoatProtection,entryLipidenvelopeinsomevirusesSmall-(20-400nm)ObligateintracellularparasitesGROWTHONARTIFICIALMEDIADIVISIONBYBINARYFISSIONCONTAINSBOTHRNAANDDNACONTAINSRIBOSOMESCONTAINSMURAMICACIDSENSITIVETOANTIBIOTICSBACTERIA++++++MYCOPLASMA++++-+RICKETTSIA-+++++CHLAMYDIA-+++-+VIRUSES---(-)*--*Thearenavirusfamilyappearsto‘accidentally’packageribosomes,buttheseappeartoplaynoroleinproteinsynthesis.ConsequencesHea