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1,Mycology真菌学,2,Fungiareeukaryotes.Theypossessanucleusenclosedbyanuclearmembrane,acellwall(chitin几丁质andglycoproteins糖蛋白),endoplasmicreticulum,Golgiapparatusandmitochondria.MedicalMycologyisthesubjectonpathogenicfungi.,Generalintroduction,3,Thereareapproximately70,000recognizedspeciesoffungi.Mostarebeneficialtohumankind.(e.g.,Theproductionoffood,antibioticsandimmunosuppressivedrugs.Usedasmodelsystemsinmolecularbiology)Somefungiactastheplantandanimalpathogensintheagriculturalindustry.About300speciesoffungiinvolvehumaninfections.,Roleoffungiinnature,Aspergillusoryzae米曲霉,Ciclosporin环孢素,4,Basicunderstandingoffungi,5,Comparisonoffungiandbacteria,FungiCharacteristics,Thefungiareclassifiedintotheirownseparatekingdom,KingdomFungi(Myceteae真菌界)withthefollowingcharacteristics:Eukaryoticorganisms.Rigidcellwallcomposedofchitin.Lackchloroplast叶绿体toproducechlorophyll叶绿素.Reproducebymeansofsporeswhichcanbeproducedeitherasexuallyorsexually.Fungalsporesgerminatetoproduceeitheramycelia霉orayeast酵母,orboth(dependingontheconditions).,CellularMorphology,Apathogenicfungicanexisteitherasyeastsorashyphae菌丝(mycelium).Amassofhyphaeiscalledmycelia(molds).,yeast,Mycelia,8,Mycelia(molds),9,Yeastsareunicellularorganismswithouthyphae.Theyeastspropagateusuallybyblastoconidiaformation芽生(budding)andrarelybybinaryfission二分裂.Iftheyeastcontinuetopropagatebyformingmoreandmorebuds,butdonotdetachfromoneanother,theywillproduceelongatedformssimilartohyphaecalledaspseudohyphae假菌丝.,Yeasts,A.Yeastcellspropagatingbyblastoconidia/buddingB.YeastdividingbybinaryfissionC.Developmentofpseudohyphae,10,Moldshavetwodifferentstructuralparts:HyphaeandSpores.Hyphaearemulti-cellularfilamentousstructures.Structurally,accordingtohyphaedoordonothavesepta横隔theyarecalledseptateornonseptatehyphae.Functionally,threekindsofhyphaearedefined:vegetative,aerialandreproductivehyphae.Hyphaeformbranchesandthepatternofbranchingishelpfulformorphologicalidentification.Hyphaeproliferateasexuallyand/orsexually.,Molds,Coenocytic多核,septate,AseptateHyphae,SeptateHyphae,13,Vegetativemycelia:penetrateintothemediuminordertoobtainnutrients,Aerialmycelia:extendfromthemediumintotheair.,Reproductivemycelia:thepartofaerialmyceliathatcanproducespores,14,Anaerialhyphaeoftenproducesasexualpropagatesnamedasasexualspores(producedbyonecell).Conidium分生孢子isthemostcommonasexualspore.Relativelylargeandcomplexconidiaaretermedasmacroconidia,whilethesmallerandsimplerconidiaaretermedasmicroconidia.Whenmanyconidiaareenclosedinasac,itiscalledasendospores/sporangiospore包囊孢子.Thesize,shapeandlocationofsporesareusedinlaboratorytoidentifysomespeciesoffungi.,Spores,15,包囊孢子,分生孢子,叶状孢子,关节孢子,芽生孢子,厚膜孢子,16,Thus,amoldismulticellularmicrobescomposedoftwoparts:sporeandhypha.,Hypha,spore,Sporangiospores,SporangiumwithSporangiospores,Conidia,管,分生孢子梗,小囊,Conidia,21,Culture&Colonymorphology,Sabouraud沙保culturemedium.OptimalpH4-6.Optimaltemperature22-28,while37forsomedeeppathogenicfungi.Aerobic.,22,Typesofcolonies:1.Yeasttypecolony酵母型菌落areusuallysoft,round,2-3mminsizeandcreamcolored,smooth.2.Yeast-liketypecolony类酵母型菌落issimilartoyeasttypecolonybutformspseudohyphae.3.Filamentoustypecolony丝状型菌落havespecialfeaturessuchasvarioushyphaeandspecialpigmentation.Unicellularfungi(onecellmeansonefungus,e.g.,yeastfungus)formyeastoryeast-likecolony.Multicellularfungi(manycellsconsistonefungus,e.g.,mold)formfilamentoustypecolony.,23,Unicellularfungi,24,Multicellularfungi,25,Multicellularfungi,26,Dimorphicfungi双相性真菌,Afewoffungioccurinboththeyeastandmycelial(filamentous)forms.Thesefungiiscalledasdimorphicfungi.Yeastform:aparasitic寄生orpathogenicform.Thisformisusuallyseenintissueofpatientsorculturedat37.Conversiontoyeastformappearstobeessentialforpathogenicity.Mycelialform(filamentousform):asaprophytic腐生form.Thisistheformexistedinnatureorculturedat25.,27,Yeasttypecolony,Filamentoustypecolony,28,DimorphicFungi,25oC,37oC,29,ClinicalManifestations,30,Fungaldiseasesinhumantendtoberelativelybenignandfewoffungaldiseasesarelife-threatening.Fungaldiseasesareanincreasingproblemduetotheuseofantibacterialandimmunosuppressiveagents.Individualswithanalteredbacterialfloraorcompromiseddefensemechanismeasilyhaveopportunisticfungalinfectionsthanhealthypeople.,Fungaldiseases,Mycosis霉菌病:Adiseasecausedbyafungus.,31,Themajorclinicalmanifestationsforfungaldiseases:Hypersensitivity超敏反应:anallergicreactiontomoldsandspores.Mycotoxicosis真菌毒素中毒:poisoningofhumanandanimalsbyfoodsandfeedscontaminatedwithmycotoxins.Infectiousdiseases:causedbyexogenouspathogenicfungi致病性orendogenousfungi(opportunisticinfections)机会致病性.Inducingtumors:Somemycotoxinscaninducetumors(e.g.,aflatoxin黄曲霉毒素producedbyAspergillusflavuscauseslivercancer).,32,Anti-fungusImmunity&fungalInfectiousdiseases,33,Ingeneral,humanshaveahighlevelofinnateimmunitytofungiandmostofthefungalinfectionsaremildandself-limiting.ExogenouspathogensOpportunisticpathogens,34,Fortheexogenouspathogenicfungi,thecausedinfectionsareclassifiedaccordingtothetissuelevels:A.Superficialmycoses表皮真菌病B.Systemicmycoses全身性真菌病,TineaVersicolor花斑癣,A.Superficialmycoses:theinfectionslimitedtotheoutlayersofskinandhair.,Commonsuperficialmycosis:,TineaVersicolor,Commonsuperficialfungalinfectionthatisseenworldwide.Incertaintropicalenvironments,itmayaffectupto60%ofthepopulation.CausedbyMalasseziafurfur糠秕状鳞斑癣菌,TineaVersicolor,Worldwidedistribution:Mostcommonintropicalclimates.Moreprevalentinsummermonthsintemperateclimates.Presentsmostofteninyoungadults(20-40yearsofage).F:M=2:1.Humaninfectionisthoughttoresultfromthedirectorindirecttransferofinfectedkeratinousmaterialfromonepersontoanother.,TineaVersicolor,Chronicmultipleirregularareasofhypo-orhyper-pigmentation.Colorvariesfrompinktoyellow,yellow-brown,orevendarkbrownindark-skinnedpatients.Infairskinnedindividuals,lesionscanappearhyperpigmentedbrownonwhite.Usuallyonseborrheicareasofbody.Thecircularmacularlesionscanbecomeconfluent.Surfacecoveredbyafinescalewhichcanbemademorevisiblebyscratchingwithafingernail.,TineaVersicolor,ConditionsPredisposing易患toTineaVersicolor,GreasyskinHyperhidrosis多汗ImmunosuppressionincludingAIDSDiabetesmellitus糖尿病Pregnancy,HistologyofTineaVersicolor,Stratumcorneum角质层containsyeastsandshortseptatehyphae(=“spaghettiandmeatballs”).,Malasseziafurfur“SpaghettiandMeatballs”,TineaVersicolor,TineaVersicolor,45,B.Systemicmycoses:theinfectionsoriginateprimarilyinthelungandthenmayspreadtomanyorgansystems.Thecommonfungicausingsystemicmycosesdescribedasthefollowing:Cryptococcusneoformans新生隐球菌Histoplasmacapsulatum荚膜组织胞浆菌Blastomyesdermatitides皮炎芽生菌Paracoccidiodesbrasiliensis巴西副球孢子菌,46,Oval,buddingyeastsurroundedbyacharacteristicwidepolysaccharidecapsule荚膜多糖.,Cryptococcusneoformans,C.neoformanswithcapsulesnegativelystainedbyInk,47,Cryptococcusneoformanscausescryptococcosis隐球菌病,asub-acuteorchronicinfectionpresentsinlungs,boneandskin,andmostcommonlymanifestsasameningitis脑膜炎.ThemeningitiscausedbyC.neoformanshasaprolongedevolutionofseveralmonthsandarehighlyfatal.Thereisnohumantohumantransmission.Infectionfollowsinhalationofpigeonorchickendroppingscontainingthemicrobe.,48,Opportunisticmycoses,Patientsorindividualswithimmunedeficiencyeasilysufferingfromopportunisticmycosescausedbyfungibelongingtonormalflora.Themajorpathogenscausingopportunisticmycosesaredescribedasthefollowing:Candida假丝酵母菌属Aspergillus曲霉菌Mucor毛霉菌,49,8speciesinthegenusCandidacaninfecthumans.Thediseaseiscalledascandidiasis.Amongthe8pathogenicspecies,Candidaalbicans假丝酵母菌isthemostcommonspeciestocausediseasesinskin,mucosa,internalorgansandcentralnervoussystem.Candidaalbicanscanbefoundin40-80%ofnormalhumanbeings.Itispresentinmouthandintestine.Candidaalbicansisdimorphicfungus.,Candidaalbicans,50,HyphaeofCandidaalbicans,Oralthrush,Oralthrush鹅口疮isatypicalandcommondiseasecausedbyCandidaalbicans,52,Fungihavestrongresistance
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