General Mycology PDF

GENERAL MYCOLOGY Dr. Abdelwahid Ali  By the end of this lectures you should know the following about fungi (yeast and molds); 1- Structure and growth. 2- Pathogenesis. 3- Toxins and Allergies. 4- Laboratory Diagnosis. 5- Antifungal Therapy. MYCOLOGY: Is study of fungi and the diseases t...

GENERAL MYCOLOGY Dr. Abdelwahid Ali  By the end of this lectures you should know the following about fungi (yeast and molds); 1- Structure and growth. 2- Pathogenesis. 3- Toxins and Allergies. 4- Laboratory Diagnosis. 5- Antifungal Therapy. MYCOLOGY: Is study of fungi and the diseases they cause. Mykues means fungus. More than 1000 spp. only about 100 are pathogenic. Structure & growth of fungi  Fungi are eukaryotes and  differ from bacteria in that : 1. Their cell wall contain chitin which is not sensitive to antibiotics. 2. The fungal cell membrane contain ergosterol on which antifungal drugs act. 3. They have true nucleus. FUNGI ARE BEBIFIT IN:  Production of antibiotic’  Fermentation of carbohydrate.  Decompostion of dead animals.  Used as food in some society. THE HARMFULL EFFECTS OF FUNGI  Spoil foods [ Food poisoning].  Produce toxin and cause disease (Mycotoxicosis).  The fungi may be :-  Saprophyte: live in dead animals.  Parasite : cause disease in animals and human. The anatomy of fungi :-  Hyphae: Elongated unit and multicellular which either be septate or nonseptate hyphae.  Mycelium :- (group of hyphae ); Divided into two parts 1- Aerial :for reproduction and growth. 2-Vegetative: For absorption of nutrition. Structure and Growth  Fungi are eukaryotic organisms with two medically important cell structures;  1- It’s cell wall consists primarily of chitin (instead of bacterial peptidoglycan), chitin is a polysaccharide, β- glucan is the one of medical importance as the site of action caspofungin (antifungal drug). 2– It’s cell membrane contains ergosterol, in contrast to the human cell membrane, which contains cholesterol. The selective action of amphotericin B and azole drugs (such fluconazole and ketoconazole) on fungi is based on this difference in membrane sterols.  Fungi are three types:-  1- Yeasts; grow as single cell (unicellular fungus) that reproduce by asexual budding  2- Molds; are relatively simple multicellular fungi, they grow as long filaments (hyphae) and form a mat (mycelium), forming either; a- Septate hyphae with transverse walls, or b- Nonseptate hyphae are multinucleated (coenocytic) witout transverse wall. 3- Medically important fungi are thermally dimorphic (form different structures at different temperature). They exist as molds in environment at ambient temperature, and as yeasts in human tissues at body temperature. PHYSIOLOGY  Temperature :-  The fungi grow in a wide range of temp.  0  70c°,  but pathogenic fungi from 20—40c°. (MESOPHLIC ). Some superficial, grow on the surface of the body at 25 c, and others grow systemically inside the body at 37c°.  Above 50c° called Thermophilic. Oxygen requirement:- -Most fungi are obligate aerobes. -Some fungi are facultative anaerobes. -No fungi are obligate anaerobes. Nutrition:- All fungi require a preformed organic source of carbon (associated with decaying matter) therefore the natural habitat of most fungi is environment except Candida albicans, which is part of human normal flora. Reproduction:- 1- Sexually:- by mating and forming sexual spores as follow; a- Zygospores; are single large spores with thick walls (Phycomycete- non septated hyphae- they can reproduce asexually by sporangiospores). b- Ascospores; are formed in a sac called ascus forming from 4 to 8 ascus (Ascomycete- septated hyphae- they reproduce asexually forming conidia). c- Basidiospores; are formed externally on the tip of a pedestal called a basidium, no asexual reproduction and non pathogenic. 2- Asexualiy:- classified as fungi imperfecti, most of medical interest propagate asexually by forming conidia from the sides or ends of specialized structures. According to their shape, color, and arrangement, conidia identified into the following:- a- Arthrospores; arise by fragmentation of the ends of hyphae, and are the mode of transmission of Coccidioides immitis. b- Chlamydospores; are rounded, thick-walled, and quite resistant (the terminal chlamydospores of Candida albicans aids in its identification). c- Blastospores; formed by budding process ( some yeasts, e.g C. albicans can form multiple buds that do not detach producing sausagelike chains called pseudohyphae, used for identification-Germ tube test). d- Sporangiospores; are formed within a sac (sporangium) on a stalk by molds such as Rhizopus and Mucor. Pathogenesis  The responses of the immune system to many fungal infections are granulomas formation, producing major systemic fungal diseases e.g.: 1- Coccidioidomycosis. 2- Histoplasmosis. 3- Blastomycosis. * Cell-mediated immune response is involved in granuloma formation. * Acute suppuration, characterized by the presence of neutrophils in the exudate, also occurs in certain fungal diseases such as aspergillosis and sporotrichosis. * Activation of the cell-mediated immune system results in a delayed hypersensitivity skin test response to certain fungal antigens injected intradermally.  A positive skin test indicates exposure to fungal antigen. It does not imply current infection, because the exposure may have occurred in the past.  A negative skin test means unlikely diagnosis unless the patient is immunocompromised.  Most people carry Candida as normal flora, so skin test for Candida antigens used to determine if cell-mediated immunity is normal or not.  Candida and dermatophytes need damage skin to establish, so intact skin is effective host defense against them.  Fatty acids in the skin inhibit dermatophyte growth.  Hormone-associated skin changes at puberty limit ringworm of the scalp caused by Trichophyton.  The normal flora of the skin and mucous membranes suppress fungi.  Inhibition of normal flora (e.g. by antibiotic) leads to overgrowth of fungi such as C. albicans.  Host defenses in respiratory tract are; -the mucous membranes of nasopharynx which trap inhaled fungal spores. and, -alveolar macrophages. Circulating IgG and IgM are produced in response to fungal infection (protective role from disease is uncertain). The cell-mediated immune response is protective, its suppression causes; - Reactivation and dissemination of asymptomatic fungal infection. - Disease caused by opportunistic fungi. Fungal Toxins and Allergies  Fungal diseases are:- 1- Mycotic infections. 2- Mycotoxicoses; caused by ingested these toxins:- a- Amanitin and phalloidin; by Amanita mushrooms, most potent hepatotoxins. b- Ergotism; by mold Claviceps purpurea, cause pronounced vascular and neurologic effects. c- Aflatoxins; by Aspergillus flavus, causing hepatic carcinoma. 3- Allergies to fungal spores; particularly of Aspergillus, which lead to immediate hypersensitivity response causing the following clinical manifestation:- a- Asthmatic reaction (rapid bronchoconstriction mediated by IgE). b- Eosinophilia. c- Skin test reaction (wheel and flare). Laboratory Diagnosis  There are four approaches to the laboratory diagnosis of fungal diseases:- 1- Direct microscopic examination of clinical specimens such as sputum, lung biopsy material, and skin scrapings depends on finding characteristic asexual spores, hyphae, or yeasts in the light microscope (stained with 10% KOH, India ink, fluorescent dye, or Methenamine silver). 2- Culture of the organism on Sabouraud’s agar, which facilitates the appearance of the slow- growing fungi by inhibiting the growth of bacteria in the specimen by;- i- the low ph of the medium. ii- chloramphenicol and cycloheximide that that are frequently added. 3- DNA probe tests, can identify colonies growing in culture at an earlier(rapid) stage of growth than visual detected test of colonies. 4- Serologic tests, for the presence of antibodies in the patient’s serum or spinal fluid, and useful in diagnosing systemic mycoses but less in diagnosing other fungal infections. Significant rise in antibody titer confirm the diagnosis.  Complement fixation test is the most frequently used in suspected cases of; - coccidioiomycosis. - Histoplasmosis. - Blastomycosis. * In cryptococcal meningitis, the presence of the polysaccharide capsular antigens of C. neoformans in spinal fluid detected by Latex agglutination test. Antifungal Therapy  The most effective antifungal drugs, amphotericin B and azoles, exploit the presence of ergosterol in fungal cell membranes that is not found in bacterial or human cell membranes.  Amphotericin B (Fungizone) disrupts fungal cell membranes at the site of ergosterol.  Azoles drugs inhibit the synthesis of ergosterol which is essential component of fungal membranes.  Caspofungin (Cancidas), inhibits the synthesis of β- glucan, which found in fungal cell walls but not in bacterial cell walls (human cells do not have a cell wall).