MycologyMycology解读解读 •Fungi are eukaryotes. They possess a nucleus enclosed by a nuclear membrane, a cell wall (chitin 几丁质 and glycoproteins 糖 蛋 白 ), endoplasmic reticulum, Golgi apparatus and mitochondria. • Medical Mycology is the subject on pathogenic fungi.General introduction2 •There are approximately 70,000 recognized species of fungi.•Most are beneficial to humankind. (e.g., The production of food, antibiotics and immunosuppressive drugs. Used as model systems in molecular biology) •Some fungi act as the plant and animal pathogens in the agricultural industry. •About 300 species of fungi involve human infections. Role of fungi in natureAspergillus oryzae 米曲霉Ciclosporin 环孢素3 Basic understanding of fungi4 Comparison of fungi and bacteriaFeatureFungiBacteriadiameter4 µm 1 µmnucleuseukaryoticprokaryoticcytoplasmwith mitochondria and endoplasmic reticulumwithout mitochondria and endoplasmic reticulumCell wallchitinpeptidoglycansporessexual and asexual spore for proliferationspore for survival, not for proliferation dimorphismyesNometabolismNo anaerobesAerobes or anaerobes5 Fungi CharacteristicsThe fungi are classified into their own separate kingdom, Kingdom Fungi (Myceteae 真菌界) with the following characteristics:Eukaryotic organisms.Rigid cell wall composed of chitin.Lack chloroplast 叶绿体 to produce chlorophyll 叶绿素.Reproduce by means of spores which can be produced either asexually or sexually.Fungal spores germinate to produce either a mycelia 霉 or a yeast 酵母, or both (depending on the conditions). Cellular Morphology •A pathogenic fungi can exist either as yeasts or as hyphae 菌丝 (mycelium). A mass of hyphae is called mycelia (molds) .yeastMycelia Mycelia (molds)8 •Yeasts are unicellular organisms without hyphae.•The yeasts propagate usually by blastoconidia formation 芽生 (budding) and rarely by binary fission 二分裂.• If the yeast continue to propagate by forming more and more buds, but do not detach from one another, they will produce elongated forms similar to hyphae called as pseudohyphae 假菌丝. YeastsA. Yeast cells propagating by blastoconidia / buddingB. Yeast dividing by binary fissionC. Development of pseudohyphae 9 • Molds have two different structural parts: Hyphae and Spores.• Hyphae are multi-cellular filamentous structures. • Structurally, according to hyphae do or do not have septa 横隔 they are called septate or nonseptate hyphae.• Functionally, three kinds of hyphae are defined: vegetative, aerial and reproductive hyphae. • Hyphae form branches and the pattern of branching is helpful for morphological identification.• Hyphae proliferate asexually and/or sexually.MoldsCoenocytic多核septate10 Aseptate Hyphae Septate Hyphae Vegetative mycelia:penetrate into the medium inorder to obtain nutrientsAerial mycelia: extend from the medium into the air.Reproductive mycelia: the part of aerial mycelia that can produce spores13 • An aerial hyphae often produces asexual propagates named as asexual spores (produced by one cell). Conidium 分生孢子 is the most common asexual spore. Relatively large and complex conidia are termed as macroconidia, while the smaller and simpler conidia are termed as microconidia. When many conidia are enclosed in a sac, it is called as endospores / sporangiospore 包囊孢子. •The size, shape and location of spores are used in laboratory to identify some species of fungi. Spores14 包囊孢子分生孢子叶状孢子关节孢子芽生孢子厚膜孢子15 • Thus, a mold is multicellular microbes composed of two parts: spore and hypha.Hyphaspore16 Sporangiospores Sporangium with Sporangiospores Conidia管管分生孢子梗分生孢子梗小囊小囊 Conidia Culture & Colony morphologySabouraud 沙保沙保 culture medium.Optimal pH 4-6.Optimal temperature 22-28 ℃℃, while 37 ℃℃ for some deep pathogenic fungi.Aerobic.21 •Types of colonies: 1. Yeast type colony 酵母型菌落 are usually soft, round, 2-3 mm in size and cream colored，smooth. 2. Yeast-like type colony 类酵母型菌落 is similar to yeast type colony but forms pseudohyphae. 3. Filamentous type colony 丝状型菌落 have special features such as various hyphae and special pigmentation.•Unicellular fungi (one cell means one fungus, e.g., yeast fungus) form yeast or yeast-like colony.•Multicellular fungi (many cells consist one fungus, e.g., mold) form filamentous type colony.22 Unicellular fungi23 Multicellular fungi24 Multicellular fungi25 Dimorphic fungi 双相性真菌双相性真菌• A few of fungi occur in both the yeast and mycelial (filamentous) forms. These fungi is called as dimorphic fungi. Yeast form: a parasitic 寄生 or pathogenic form. This form is usually seen in tissue of patients or cultured at 37 ℃℃. Conversion to yeast form appears to be essential for pathogenicity. Mycelial form (filamentous form): a saprophytic 腐生 form. This is the form existed in nature or cultured at 25 ℃.℃.26 Yeast type colonyFilamentous type colony27 Dimorphic Fungi25o C37o C28 Clinical Manifestations29 • Fungal diseases in human tend to be relatively benign and few of fungal diseases are life-threatening. • Fungal diseases are an increasing problem due to the use of antibacterial and immunosuppressive agents. Individuals with an altered bacterial flora or compromised defense mechanism easily have opportunistic fungal infections than healthy people. Fungal diseasesMycosis 霉菌病霉菌病: A disease caused by a fungus.30 The major clinical manifestations for fungal diseases:◇◇Hypersensitivity 超超敏敏反反应应：：an allergic reaction to molds and spores.◇◇Mycotoxicosis真真菌菌毒毒素素中中毒毒: poisoning of human and animals by foods and feeds contaminated with mycotoxins.◇◇Infectious diseases: caused by exogenous pathogenic fungi 致病性 or endogenous fungi (opportunistic infections) 机会致病性. ◇◇Inducing tumors: Some mycotoxins can induce tumors (e.g., aflatoxin黄黄曲曲霉霉毒毒素素produced by Aspergillus flavus causes liver cancer).31 Anti-fungus Immunity& fungal Infectious diseases32 •In general, humans have a high level of innate immunity to fungi and most of the fungal infections are mild and self-limiting. •Exogenous pathogens •Opportunistic pathogens33 •For the exogenous pathogenic fungi, the caused infections are classified according to the tissue levels: A. Superficial mycoses 表皮真菌病表皮真菌病 B. Systemic mycoses 全身性真菌病全身性真菌病34 Tinea Versicolor花斑癣花斑癣 A. Superficial mycoses: the infections limited to the out layers of skin and hair. Common superficial mycosis: Tinea VersicolorCommon superficial fungal infection that is seen worldwide. In certain tropical environments, it may affect up to 60% of the population. Caused by Malassezia furfur 糠秕状鳞斑癣菌 Tinea VersicolorWorldwide distribution:Most common in tropical climates.More prevalent in summer months in temperate climates.Presents most often in young adults (20-40 years of age).F:M = 2:1.Human infection is thought to result from the direct or indirect transfer of infected keratinous material from one person to another. Tinea VersicolorChronic multiple irregular areas of hypo- or hyper-pigmentation.Color varies from pink to yellow, yellow-brown, or even dark brown in dark-skinned patients.In fair skinned individuals, lesions can appear hyperpigmented – brown on white.Usually on seborrheic areas of body.The circular macular lesions can become confluent.Surface covered by a fine scale which can be made more visible by scratching with a fingernail. Tinea Versicolor Conditions Predisposing 易患 to Tinea VersicolorGreasy skinHyperhidrosis 多汗Immunosuppression including AIDSDiabetes mellitus 糖尿病糖尿病Pregnancy Histology of Tinea VersicolorStratum corneum角质层角质层 contains yeasts and short septate hyphae (= “spaghetti and meatballs”). Malassezia furfur“Spaghetti and Meatballs” Tinea Versicolor Tinea Versicolor B. Systemic mycoses: the infections originate primarily in the lung and then may spread to many organ systems. ◇◇ The common fungi causing systemic mycoses described as the following: Cryptococcus neoformans 新生隐球菌 Histoplasma capsulatum 荚膜组织胞浆菌 Blastomyes dermatitides 皮炎芽生菌 Paracoccidiodes brasiliensis 巴西副球孢子菌45 Oval, budding yeast surrounded by a characteristic wide polysaccharide capsule 荚膜多糖. Cryptococcus neoformansC.neoformans with capsules negatively stained by Ink46 ◇◇Cryptococcus neoformans causes cryptococcosis 隐隐球球菌菌病病, a sub-acute or chronic infection presents in lungs, bone and skin, and most commonly manifests as a meningitis 脑膜炎.◇ ◇ The meningitis caused by C.neoformans has a prolonged evolution of several months and are highly fatal. ◇◇ There is no human to human transmission. Infection follows inhalation of pigeon or chicken droppings containing the microbe.47 Opportunistic mycoses◇ ◇ Patients or individuals with immune deficiency easily suffering from opportunistic mycoses caused by fungi belonging to normal flora. ◇ ◇ The major pathogens causing opportunistic mycoses are described as the following:• Candida 假丝酵母菌属• Aspergillus 曲霉菌• Mucor 毛霉菌48 ◇ ◇ 8 species in the genus Candida can infect humans. The disease is called as candidiasis. ◇ ◇ Among the 8 pathogenic species, Candida albicans 假丝酵母菌 is the most common species to cause diseases in skin, mucosa, internal organs and central nervous system. ◇ ◇ Candida albicans can be found in 40-80% of normal human beings. It is present in mouth and intestine. ◇◇Candida albicans is dimorphic fungus. Candida albicans49 Hyphae of Candida albicans50 Oral thrush Oral thrush 鹅鹅口口疮疮 is a typical and common disease caused by Candida albicans • Fungi have strong resistance to dry, sunlight, UV light and many chemical agents, but much sensitive to wet heat.• The antibiotics to treat fungal infectious diseases are quite different compared to those to cure infectious bacterial diseases: amphotericin B（两性霉素B ）, anticandine（制霉菌素）, miconazole （咪康唑）, ketoconazole （酮康唑） and so on.Resistance / Drugs52 SummaryThe most important contents in this lecture:•General introduction: eukaryotes, cell wall (chitin and glycoproteins), difference between fungi and bacteria (in the table). Yeast (unicellular organism) and mold (multicellular organism) composed of spore and hypha, Sabouraud medium and the optimal pH and temperature, types of hypha and colonies, four types of fungal diseases.•Cutaneous mycoses: dermatophytes, tinea, invading the keratinized layers. •Systemic mycoses (Cryptococcus neoformans): capsule, the caused major disease (meningitis), transmission route. •Opportunistic mycoses (Candida albicans): Oral thrush, diagnostic feature of germ tube.53 结束结束 。