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Medical Mycology 1 Comparison of fungi and bacteria Feature Fungi Bacteria diameter 4 µm 1 µm nucleus eukaryotic prokaryotic cytoplasm with mitochondria and without mitochondria and endoplasmic reticulum endoplasmic reticulum Cell membrane sterol present sterol absent Cell wall chitin peptidoglycan spores sexual and asexual spore for proliferation spore for survival, not for proliferation dimorphism yes No metabolism Require organic carbon and no anaerobes May do not require organic carbon and maybe anaerobes 2 3 4 5 6 7 Role of fungi in nature There are approximately 70,000 recognized species of fungi. Most are beneficial to humankind. production of food antibiotics and immunosuppressive drugs used as model systems in molecular biology 8 Medical Mycology the subject on pathogenic fungi Some fungi act as the plant and animal pathogens in the agricultural industry. About 300 species of fungi cause human infections. 9 曲霉菌 假丝酵母菌 表皮癣菌 小孢子癣菌 毛癣菌 Mucor 毛霉菌 Cryptococcus neoformans 新型隐球菌 皮炎芽生菌 荚膜组织胞浆菌 巴西副孢子菌 10 Cellular Morphology Yeasts: unicellular organisms mycelia (molds): multicellular Dimorphic fungi 11 12 13 A. Yeast cells propagating by blastoconidia / budding B. Yeast dividing by binary fission C. Development of pseudohyphae 14 molds 15 • a mold is multicellular microbes composed of two parts: spore and hypha. Hypha spore 16 Dimorphic fungi • Some fungi exist in both yeast and mycelial forms. These fungi are called dimorphic fungi. Yeast form: a parasitic or pathogenic form. This form is usually seen in tissue of patients. Can be cultured at 37 ℃. Conversion to yeast form appears to be essential for pathogenicity. Mycelial form: a saprophytic form. This is the form existing in nature. Can be cultured at 25 ℃. 17 Culture & Colony morphology Sabouraud culture medium. Optimal pH 4-6. Optimal temperature 22-28 ℃, 37 ℃ for certain pathogenic fungi. Aerobic. 18 Unicellular fungi 19 Multicellular fungi 20 Resistance • Fungi have strong resistance to dryness, sunlight, UV light and many chemical agents, but much sensitive to wet heat. 21 Drugs • The antibiotics to treat fungal infectious diseases are quite different compared to those to cure bacterial infectious diseases: amphotericin B (两性霉素B), anticandine (制霉菌 素), miconazole (咪康唑), ketoconazole (酮康唑) etc. 22 Clinical Manifestations 23 Major clinical manifestations of fungal diseases: ◇Hypersensitivity:an allergic reaction to molds and spores. ◇Mycotoxicosis: poisoning of human and animals by food contaminated with mycotoxins. ◇Infectious diseases: caused by exogenous pathogenic fungi or endogenous fungi (opportunistic infections). ◇Inducing tumors: Some mycotoxins can induce tumors (e.g., aflatoxin causes liver cancer) (黄曲霉素). 24 Anti-fungus Immunity & fungal Infectious diseases 25 •In general, humans have a high level of innate immunity to fungi and most of the fungal infections are mild and self-limiting. •For the exogenous pathogenic fungi, the infections are classified according to where the infections take place: A. Superficial mycoses B. Cutaneous mycoses C. Subcutaneous mycoses D. Systemic mycoses 26 A. Superficial mycoses: Infections are limited to the hair or the outermost layers of skin. 27 28 29 30 31 32 B. Cutaneous mycoses: • Fungi invade the keratinized layers (角化层) of skin, hair and nails and the diseases are limited in these layers. • • The fungi causing these diseases are termed dermatophytes (皮肤癣真菌). The diseases are referred to as tinea (癣病). 33 34 •All tinea are caused by members of three genera: Trichophyton (毛癣菌) Epidermophyton (表皮癣菌) Microsprum (小孢子癣菌) •Unlike the superficial mycoses, cellular immune responses may be evoked 35 common cutaneous mycoses: 36 37 C. Subcutaneous mycoses: The infections involve the dermis, subcutaneous tissue, muscle and fascia. 38 39 40 41 42 43 D. Systemic mycoses: the infections originate primarily from the lung and then spread to many other organs 44 Cryptococcus neoformans Oval, budding yeast surrounded by characteristic thick polysaccharide capsule. 45 C. neoformans with capsule is negatively stained by India Ink 46 Disease Cryptococcosis Acute or chronic infections in the lung, bone and skin, and meningitis meningitis can last several months and are highly fatal 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 are easily suffering from opportunistic mycoses caused by fungi belonging to normal flora. 48 Candida albicans can be found in 40- 80% of normal human beings. It is present in mouth, intestine and vagina. Candida albicans is dimorphic fungus. Candida albicans can show germ tubes with special shape, which used as a diagnostic feature of the microbe. 49 50 Pseudohyphae and hyphae of Candida albicans using Methenamine Silver Stain. 51 Oral thrush is a typical and common disease caused by Candida albicans 52