医学微生物学资料：Pathogenic Fungi

1、Pathogenic FungiWhats the difference between fungus and bacteria? what are the factors that may account for the increasing of Mycoses?What are the common themes in the immunity and chemotherapy of fungal diseases?Which factors should be considered when we select (an) antifungal(s) for a patient?33Fu

2、ngus 真菌Hypha /hyphae 菌丝Mycelium 菌丝体Spore 孢子Chitin 几丁质Septa 隔膜，横膈Septate hyphae 有隔菌丝Aseptate hyphae无隔菌丝Eukaryocyte 真核细胞Prokaryotic 原核的Ergosterol 麦角固醇Yeast 酵母酵母菌Budding : 芽殖Conidia 分生孢子Ascospore 囊孢子Pseudohypha 假菌丝Granulomatous response 肉芽肿反应Pyogenic response 化脓性反应Induration 硬化Aflatoxin 黄曲霉素Amanitin 鹅膏

3、菌素Cocidodomycosis球孢子菌病Cryptococcus neoformans 新生隐球菌Opportunistic fungal infection 机会性真菌感染Primary fungal infection 原发性真菌感染Candida albicans 白假丝酵母菌 Vocabulary 44Fungus kingdomFungus phylum subphylum Mastigomycotina Zygomycotina接合菌亚门 mucor 毛霉菌 Ascomycotina 子囊菌亚门 histoplasma 组织胞浆菌 Basodopmycotina 担子菌亚门 C

4、. neoformans 星形隐球菌 Deutemycotina 半知菌亚门 coccidiodes 球孢子菌55Fungi are everywhere in our daily life 66Fungal diseases are increasingLimits of resolutionClasses of organisms50,000-V electron microscope 0.003mBacteria 0.1-10mMicroscopic protozoa and fungi, 4-40mViruses0.03-0.3mLight microscope 0.2mUnaided

5、 human eye 40mSize (m)Comparison of fungi and bacteriaGeneral Characteristics of FungiSize : varies immensely. bacteria size macroscopically visible size 99Comparison of fungi and bacteria fungi bacteriaSize 4m about 1mNucleus eukaryotic prokaryoticCell membrane sterols no sterolsCell wall chitin PG

6、Spores for reproduction not1010Nucleus ：Cytoplasm : Cytoplasmic membrane: ergosterol （麦角固醇）Cell wall : polysacchrides mannan, chitin, -glucanStructure 1111Fibrillar proteinsMannoprotein Glucan Chitin Cytoplasmic membrane The fungi cell wall Hyphae： multicellular branching structures,Mycelium： Integr

7、ated masses of hyphae Each hypha is about 5-10 m wide.myceliumUnicellular fungi multicelluar fungi sporesHyphae of fungiBlastoconidiaAscospores BlastoconidiumPseudohypha Ascus Growth of yeast or yeast-like fungi (budding)Yeast formsVegitative mycelium Nucleus Sporangiospores Arthroconidia Conidia Sp

8、orangia Nucleus Microconidia Macroconidia Conidiophore Nonseptate hyphaChlamydoconidia Ssepta Kenneth J.Ryan/C.Geore Ray. Sherris Medicial Microbiolgy Fourth edition :634Growth of Mold 1616？ ？ ?Where do those bad guys come from?17171818Airconditioner system1919 person to person transmission animal t

9、o person transmission inhalation from environment endogenous infection. eg. Candiada albicans. Transmission of fungus infectionPrimary pathogensOpportunistic pathogens Candia spp., Aspergillus sppthe state of the host is of primary importanceAttention Pathogenesis of fungusGranulomatous responsePyog

10、enic responseInduration ( delayed hypersensitivity)Toxins like aflatoxin(黄曲霉素), amanitin(鹅膏菌素) Allergic disease ( IgE-mediated hypersensitivityGastrointestinal toxicity Bone marrow toxicityEndocrine toxicity Neurotoxcicity Lung toxicity Allergy Hemorrhage Tumor Hepatoxicity Hepatitis Hepatoma Immune

11、 system toxicityNephrotoxicity Contaminated grain or other food stuffMould in the enviroument Aspergillus sppFusarium sppClaviceps sppPenicillin sppStachybotrys sppMycotoxins in particulatesContact Inhaletion Ingestion Mycotoxins an mycotoxicoses Immunity Humoral immunity Cryptococcus neoformans, ca

12、ndida albicansCoccidioides immitis coccidioidomycosis Cellular immunity Systemic disease :steroid treatment,leukemia, hodgkins disease, and acquired immunodeficiency syndrome.Cell-medicated immunity to fungal infectionsT helper cellCytokines Bound cytokinesInfection of fungusDifferent organisms or s

13、ystems involvedDifferent manifestations subacute to chronic acute diseasesystemic disease26Classification of fungal diseasesSuperficial mycosesCutaneous,hair,and nail mycosesSubcutaneous mycosesSystemic mycoses27Superficial mycosescutaneous, hair, and nail mycosesTinea pedisTinea captis28Subcutaneou

14、s mycosesLaboratory diagnosis Specimen sampling skin ， nails，hairs; blood, CSF, sputum and other secretions Microscopy of slide samples 10-20%KOH treatmentDiagnosis CultureMedia: Sabourauds agar , selective mediaTemperature :pH：4.06.0Laboratory diagnosis Serologic tests : To detect fungus antigen or

15、 antibody Molecular biology methods: Based on G+C mol%, RFLP(ristriction fragment length polymorphism ) analysis, Laboratory diagnosis Principles of anti-fungus chemotherapyMost opportunistic fungal infections are self-limited and re-building of normal flora is essential for the infection controlThe

16、 chemotherapy is specially needed for patients with poor immunity Anti-fungal drugs can be applied locally or systemicallyResistance to anti-fungal drugs: concepts are similar to bacteria resistance Principles of anti-fungus Chemotherapy Cell wallInhibitors of Glucan synthesis : Echinocandins:Caspof

17、ungin Inhibitors of chintin synthesis:Nikkomycin Cell membrane Inhibitors of ergosterol synthesis:AzolesAllylamines Direct membrane damage:Polyenes : amphotericin BDisruption of microtubules and inhibition of mitosis :Griseofulvin Nucleic acid synthesis :Flucytosine Inhibition of protein synthesis :SordarinsAzasordarins Sites of acti