Lecture 14 Cutaneous and Subcutaneous Mycoses PDF
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2023
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This document is a lecture on Cutaneous and subcutaneous Mycoses, covering basic concepts of fungi, mycology structure, and fungal cell walls. It includes information about mycoses, and different fungal forms like yeasts and molds, as well as hyphae.
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Lecture 14 Cutaneous and subcutaneous Mycoses Fungi- basic concepts Mycology is the study of fungi. Approximately 80,000 species of fungi have been described, but fewer than 400 are medically important, and less than 50 species cause more than 90% of the fungal infec...
Lecture 14 Cutaneous and subcutaneous Mycoses Fungi- basic concepts Mycology is the study of fungi. Approximately 80,000 species of fungi have been described, but fewer than 400 are medically important, and less than 50 species cause more than 90% of the fungal infections of humans and other animals. Rather, most species of fungi are beneficial to humankind. They reside in nature and are essential in breaking down and recycling organic matter. Some fungi greatly enhance our quality of life by contributing to the production of food and spirits, including cheese, bread, and beer. Other fungi have served medicine by providing useful bioactive secondary metabolites such as antibiotics (eg, penicillin) and immunosuppressive drugs (eg, cyclosporine) Mycology Fungi are eukaryotes with a higher level of biologic complexity than bacteria. Each fungal cell has at least one nucleus and nuclear membrane, endoplasmic reticulum, mitochondria, and secretory apparatus. Most fungi are obligate or facultative aerobes. They are spore bearing; reproducing both sexually and asexually. Fungi may be unicellular or may differentiate and become multicellular by the development of long-branching filaments. They acquire nutrients by absorption but lack the chlorophyll of plants. Structure The fungal cell has typical eukaryotic features, including a nucleus with a nucleolus, nuclear membrane, and linear chromosomes. The cytoplasm contains a cytoskeleton with actin microfilaments and tubulin-containing microtubules. Ribosomes and organelles, such as mitochondria, endoplasmic reticulum, and the Golgi apparatus, are also present. Fungal cells have a rigid cell wall external to the cytoplasmic membrane, which differs in its chemical composition from that of bacteria and plants. An important difference from mammalian cells is the sterol makeup of the cytoplasmic membrane. In fungi, the dominant sterol is ergosterol; in mammalian cells, it is cholesterol. Fungi are usually in the haploid state, although diploid nuclei are formed through nuclear fusion in the process of sexual reproduction. Fungal cell wall The chemical structure of the cell wall in fungi is markedly different from that of bacterial cells in that it does not contain peptidoglycan, glycerol, teichoic acids, or lipopolysaccharide. In their place are the polysaccharides mannan, glucan, and chitin in close association with each other and with structural proteins. Chitin and glucan give rigidity to cell wall. Mycoses The diseases caused by fungi are called mycoses. For convenience, mycoses may be classified as superficial, cutaneous, subcutaneous, systemic, and opportunistic. Grouping mycoses in these categories reflects their usual portal of entry and initial site of involvement. However, there is considerable overlap, since systemic mycoses can have subcutaneous manifestations and vice versa. Most patients who develop opportunistic infections have serious underlying diseases and compromised host defenses. Acute disease, such as that produced by many viruses and bacteria, is uncommon with fungal infections. Most mycoses are difficult to treat. Because fungi are eukaryotes, they share numerous homologous genes and gene products with their human hosts. Consequently, there are few unique targets for chemotherapy and effective antibiotics. Most pathogenic fungi are exogenous, their natural habitats being water, soil, and organic debris. The mycoses with the highest incidence—candidiasis and dermatophytosis— are caused by fungi that are part of the normal microbial flora or highly adapted to survival on the human host. Yeasts and molds Fungi grow in two basic forms, as yeasts and molds (or moulds). Growth in the mold form occurs by production of multicellular filamentous colonies. These colonies consist of branching cylindric tubules called hyphae, varying in diameter from 2 μm to 10 μm. The mass of intertwined hyphae that accumulates during active growth is a mycelium. Some hyphae are divided into cells by cross-walls or septa, typically forming at regular intervals during hyphal growth. One group of medically important molds, the zygomycetes, produces hyphae that are rarely septated. Hyphae Some fungi have septate hyphae (the hyphae are divided into cells by cross walls or septa). Some fungi have aseptate hyphae (the hyphae do not have septa). Aseptate (coenocytic) hyphae contain multinucleated cytoplasm. Yeasts and molds(2) Fungi may also grow through the development of hyphae. Which are tube like extensions of the cell. As the hyphae extend they from and inter wined mass called mycelium. A portion of the mycelium (vegetative mycelium or substrate hyphae) grows into the medium or organic substrate and absorb nutrients and acts as a root. Aerial mycelium bears reproductive conidia or spores. The hyphael walls are rigid to support inter wining network commonly called a mold. Under standardized growth conditions in the laboratory, molds produce colonies with characteristic features such as rates of growth, texture, and pigmentation. The genus—if not the species—of most clinical molds isolated can be determined by microscopic examination of the ontogeny and morphology of their asexual reproductive spores, or conidia. Yeasts are single cells, usually spherical to ellipsoid in shape and varying in diameter from 3 μm to 15μm. Most yeasts reproduce by budding. Some species produce buds that characteristically fail to detach and become elongated; continuation of the budding process then produces a chain of elongated yeast cells called pseudohyphae. Hyphae vs pseudohyphae Some fungi form structures called pseudohyphae, which differ from the hyphae in having recurring bud-like constructions and less rigid. Once again The budding yeasts reproduce asexually by budding off a smaller daughter cell; the resulting cells may sometimes stick together as a short chain or pseudohypha Yeasts and molds Initial growth from a single cell may follow in two courses, yeast and mold. The first and simplest is formation of a bud, which extends from a round or oblong parent constructs, and forms a new cell, which separate from the parent. These buds are called blastoconidia, and fungi that reproduce in this manner are called yeasts. Dimorphism In general, fungi grow either as yeasts or mold forms. Some species can grow in either yeast or mold phase, depending on environmental conditions. These species are known as dimorphic fungi. Temperature triggers shift between phases. Dimorphism is reversible and is linked to virulence. Dimorphic Fungi A few fungi, including some pathogens, can live as either yeasts or moulds, depending on growth conditions. This phenomenon is known as dimorphism and the fungi are called dimorphic fungi. When grown in vitro at room temperature (25oC), dimorphic fungi exist as moulds, producing mould colonies. When grown in vitro at body temperature (37oC), dimorphic fungi grow as yeasts and produce yeast colonies. In vivo, dimorphic fungi exist as yeasts. Fungi - Reproduction Fungi may reproduce by either asexual or sexual process. The asexual form is called anamorph, and its reproductive elements are termed conidia. Asexual reproduction forms conidia by mitosis. In sexual reproduction, the haploid nuclei of donor and recipient fuse to form a diploid nucleus, which then divides by classic meiosis. Meiosis forms sexual spores in specialized structures. Spores Spores can be readily dispersed, are more resistant to adverse conditions, and can germinate when conditions for growth are favorable. Spores can derive from asexual or sexual reproduction—the anamorphic and teleomorphic states, respectively. Asexual spores are mitotic progeny (ie, mitospores) and genetically identical. The medical fungi produce two major types of asexual spores, conidia, and, in the zygomycetes, sporangiospores. Conidia Conidiophore Morphology of reproductive conidia and spores are used for identification. Exogenously formed conidia may develop directly from the hyphae or on a special stalk- like surface the conidiophore. Conidia that develop within the hyphae are called chlamydoconidia or arthroconidia. The most common sexual spore are termed an ascospore. 4 or 8 ascospores may be found in a sac-like structure, the ascas. In some fungi, vegetative cells may transform into conidia (eg, arthroconidia, chlamydospores). In others, conidia are produced by a conidiogenous cell, such as a phialide, which itself may be attached to a specialized hypha called a conidiophore. In the zygomycetes, sporangiospores result from mitotic replication and spore Sporangiospores production within a sac-like structure called a sporangium, which is supported by a sporangiophore. Classification The fungi are classified in four phyla: Chytridiomycota, Zygomycota, Ascomycota, and Basidiomycota. The largest phylum is the Ascomycota (or ascomycetes), which includes more than 60% of the known fungi and about 85% of the human pathogens. The remaining pathogenic fungi are zygomycetes or basidiomycetes. A. ZYGOMYCOTA (ZYGOMYCETES) Sexual reproduction results in a zygospore; asexual reproduction occurs via sporangia. Vegetative hyphae are sparsely septate. Examples: Rhizopus, Absidia, Mucor, Pilobolus B. ASCOMYCOTA (ASCOMYCETES) Sexual reproduction involves a sac or ascus in which karyogamy and meiosis occur, producing ascospores. Asexual reproduction is via conidia. Molds have septate hyphae. Examples: Ajellomyces (anamorphic genera, Blastomyces and Histoplasma), Arthroderma (anamorphic genera, Microsporum and Trichophyton), Coccidioides, and yeasts (Saccharomyces and Candida). C. BASIDIOMYCOTA(BASIDOMYCETES) Sexual reproduction results in four progeny basidiospores supported by a club-shaped basidium. Hyphae have complex septa. Examples: Mushrooms, Filobasidiella neoformans (anamorph, Cryptococcus neoformans). Culturing Most fungi occur in nature and grow readily on simple sources of nitrogen and carbohydrate. The traditional mycological medium, Sabouraud’s agar, which contains glucose and modified peptone (pH 7.0), has been used because it Sabouraud agar does not readily support the growth of bacteria. Fungi Medical Significance A variety of fungi including yeasts, moulds, and some fleshy fungi, are of medical, veterinary and agricultural importance because of the diseases they cause in humans, animals, and plants. The infectious diseases of humans and animals that are caused by moulds are called mycoses Grouping of medically important fungi Grouping of medically important fungi is based on the types of tissues they parasitize and the diseases they produce. Superficial fungi - dermatophytes cause indolent lesions on skin and its appendages (ringworm or athletic foot). The subcutaneous pathogens causes infection through the skin, followed by subcutaneous spread, lymphatic spread or both. The opportunistic fungi are found in the environment or resident flora, they produce disease in certain circumstances and in compromised hosts. The systemic pathogens are the most virulent fungi and may cause serious progressive systemic diseases in previously healthy persons. SUPERFICIAL MYCOSES Superficial mycoses are fungal infections of the outermost areas of the human body – hair, nails and epidermis. PITYRIASIS VERSICOLOR Pityriasis versicolor is a chronic mild superficial infection of the stratum corneum caused by Malassezia globosa, M restricta, and other members of the M furfur complex. Invasion of the cornified skin and the host responses are both minimal. Discrete, serpentine, hyper- or hypopigmented maculae occur on the skin, usually on the chest, upper back, arms, or abdomen. The lesions are chronic and occur as macular patches of discolored skin that may enlarge and coalesce, but scaling, inflammation, and irritation are minimal. Indeed, this common Pityriasis versicolor is treated with daily affliction is largely a cosmetic applications of selenium sulfide. Topical or oral problem. azoles are also effective. TINEA NIGRA Tinea nigra (or tinea nigra palmaris) is a superficial chronic and asymptomatic infection of the stratum corneum caused by the dematiaceous fungus Hortaea (Exophiala) werneckii. This condition is more prevalent in warm coastal regions and among young women. The lesions appear as a dark (brown to black) discoloration, often on the palm. Microscopic examination of skin scrapings from the periphery of the lesion will reveal branched, septate hyphae and budding yeast cells with melaninized cell walls. Tinea nigra will respond to treatment with keratolytic solutions, salicylic acid, or azole antifungal drugs. PIEDRA Black piedra is a nodular infection of the hair shaft by Piedraia hortai. White piedra, due to infection with Trichosporon species, presents as larger, softer, yellowish nodules on the hairs. Axillary, pubic, beard, and scalp hair may be infected. Treatment for both types consists of removal of hair and application of a topical antifungal agent. Piedra is endemic in tropical underdeveloped countries. CUTANEOUS MYCOSES Cutaneous mycoses are caused by fungi that infect only the superficial keratinized tissue (skin, hair, and nails). The most important of these are the dermatophytes, a group of about 40 related fungi that belong to three genera: Microsporum, Trichophyton, and Epidermophyton. Dermatophytoses are among the most prevalent infections in the world. Although they can be persistent and troublesome, they are not debilitating or life-threatening. Cutaneous Mycoses Cutaneous mycoses are fungal infections of the living layer of the skin, the dermis. – A group of moulds collectively referred to as dermatophytes cause tinea (“ringworm”) infections. – The yeast, Candida albicans, can also cause cutaneous, oral, and vaginal infections “Ringworm” infections Dermatophytes Despite their similarities in morphology, nutritional requirements, surface antigens, and other features, many species have developed keratinases, elastases, and other enzymes that enable them to be quite host-specific. Dermatophytes are classified as geophilic, zoophilic, or anthropophilic depending on whether their usual habitat is soil, animals, or humans. Several dermatophytes that normally reside in soil or are associated with particular animal species are still able to cause human infections. Dermatophytes are acquired by contact with contaminated soil or with infected animals or humans. Epidemiology & Immunity Dermatophyte infections begin in the skin after trauma and contact. There is evidence that host susceptibility may be enhanced by moisture, warmth, specific skin chemistry, composition of sebum and perspiration, youth, heavy exposure, and genetic predisposition. The incidence is higher in hot, humid climates and under crowded living conditions. Wearing shoes provides warmth and moisture, a setting for infections of the feet. The source of infection is soil or an infected animal in the case of geophilic and zoophilic dermatophytes, respectively. Trichophytin is a crude antigen preparation that can be used to detect immediate- or delayed-type hypersensitivity to dermatophytic antigens. A. TINEA PEDIS (ATHLETE’S FOOT) Tinea pedis is the most prevalent of all dermatophytoses. It usually occurs as a chronic infection of the toe webs. Other varieties are the vesicular, ulcerative, and moccasin types, with hyperkeratosis of the sole. Initially, there is itching between the toes and the development of small vesicles that rupture and discharge a thin fluid. The skin of the toe webs becomes macerated and peels, whereupon cracks appear that are prone to develop secondary bacterial infection. When the fungal infection becomes chronic, peeling and cracking of the skin are the principal manifestations, accompanied by pain and pruritus. TINEA PEDIS (ATHLETE’S FOOT) B. TINEA UNGUIUM (ONYCHOMYCOSIS) Nail infection may follow prolonged tinea pedis. With hyphal invasion, the nails become yellow, brittle, thickened, and crumbly. One or more nails of the feet or hands may be involved. C. TINEA CORPORIS, TINEA CRURIS, AND TINEA MANUS TINEA CORPORIS TINEA CRURIS TINEA MANUS Dermatophytosis of the glabrous skin commonly gives rise to the annular lesions of ringworm, with a clearing, scaly center surrounded by a red advancing border that may be dry or vesicular. The dermatophyte grows only within dead, keratinized tissue, but fungal metabolites, enzymes, and antigens diffuse through the viable layers of the epidermis to cause erythema, vesicle formation, and pruritus. The lesions expand centrifugally and active hyphal growth is at the periphery, which is the most likely region from which to obtain material for diagnosis. When the infection occurs in the groin area, it is called tinea cruris, or jock itch. Most such infections involve males and present as dry, itchy lesions that often start on the scrotum and spread to the groin. Tinea manus refers to ringworm of the hands or fingers. Dry scaly lesions may involve one or both hands, single fingers, or two or more fingers. D. TINEA CAPITIS AND TINEA BARBAE Tinea capitis is dermatophytosis or ringworm of the scalp and hair. The infection begins with hyphal invasion of the skin of the scalp, with subsequent spread down the keratinized wall of the hair follicle. Infection of the hair takes place just above the hair root. The infection produces dull gray, circular patches of alopecia, scaling, and itching. Tinea barbae involves the bearded region. Treatment Therapy consists of thorough removal of infected and dead epithelial structures and application of a topical antifungal chemical or antibiotic. To prevent reinfection, the area should be kept dry, and sources of infection, as an infected pet or shared bathing facilities, should be avoided. Treatment of TINEA CAPITIS Scalp infections are treated with griseofulvin for 4–6 weeks. Frequent shampoos and miconazole cream or other topical antifungal agents may be effective if used for weeks. Alternatively, ketoconazole, itraconazole, and terbinafine are all quite effective. Treatment of TINEA CORPORIS, TINEA PEDIS, AND RELATED INFECTIONS The most effective drugs are itraconazole and terbinafine. However, a number of topical preparations may be used, such as miconazole nitrate, tolnaftate, and clotrimazole. If applied for at least 2–4 weeks, the cure rates are usually 70–100%. Treatment should be continued for 1–2 weeks after clearing of the lesions. For troublesome cases, a short course of oral griseofulvin can be administered. SUBCUTANEOUS MYCOSES The fungi that cause subcutaneous mycoses normally reside in soil or on vegetation. They enter the skin or subcutaneous tissue by traumatic inoculation with contaminated material. In general, the lesions become granulomatous and expand slowly from the area of implantation. Extension via the lymphatics draining the lesion is slow except in sporotrichosis. These mycoses are usually confined to the subcutaneous tissues, but in rare cases they become systemic and produce life-threatening disease. Subcutaneous mycosis Sporotrichosis Chromoblastomycosis Phaeohyphomycosis Mycetoma Lobomycosis Rhinosporidiosis SPOROTHRIX SCHENCKII Sporothrix schenckii is a thermally dimorphic fungus that lives on vegetation. It is associated with a variety of plants—grasses, trees, sphagnum moss, rose bushes, and other horticultural plants. At ambient temperatures, it grows as a mold, producing branching, septate hyphae and conidia, and in tissue or in vitro at 35–37 °C as a small budding yeast. Following traumatic introduction into the skin, S schenckii causes sporotrichosis, a chronic granulomatous infection. The initial episode is typically followed by secondary spread with involvement of the draining lymphatics and lymph nodes. Sporotrichosis This is a chronic infection involving cutaneous, subcutaneous and lymphatic tissue It is frequently encountered in gardeners, forest workers and manual laborers Causative agent: The thermally dimorphic fungus Sporothrix schenckii The fungus is found in soil, decaying woods, thorns and on infected animals including rats, cats, dogs and horses. Sporotrichosis Sporothrix schenckii Sporothrix schenckii Pathogenesis and clinical presentation Spore is the infective stage of the fungus It causes infection primarily on the hand or the forearm through direct contact of the skin by spores Typically, infection is introduced in skin through a penetration of thorn At the site of thorn injury, it causes a local pustule or ulcer with the nodules along the draining lymphatics There is usually little systemic illness associated with these lesions, but dissemination may occur, especially in debilitated patients. Rarely, primary pulmonary sporotrichosis results from inhalation of the conidia. This manifestation mimics chronic cavitary tuberculosis and tends to occur in patients with impaired cell mediated immunity. Treatment In some cases, the infection is self-limited. Although the oral administration of saturated solution of potassium iodide in milk is quite effective, it is difficult for many patients to tolerate. Oral itraconazole or another of the azoles is the treatment of choice. For systemic disease, amphotericin B is given. Epidmiology & Control S schenckii occurs worldwide in close association with plants. For example, cases have been linked to contact with sphagnum moss, rose thorns, decaying wood, pine straw, prairie grass, and other vegetation. About 75% of cases occur in males, either because of increased exposure or because of an X-linked difference in susceptibility. The incidence is higher among agricultural workers, and sporotrichosis is considered an occupational risk for forest rangers, horticulturists, and workers in similar occupations. Prevention includes measures to minimize accidental inoculation and the use of fungicides, where appropriate, to treat wood. Animals are also susceptible to sporotrichosis. CHROMOBLASTOMYCOSIS Chromoblastomycosis (chromomycosis) is a subcutaneous mycotic infection caused by traumatic inoculation by any of five recognized fungal agents that reside in soil and vegetation. All are dematiaceous fungi, having melaninized cell walls: Phialophora verrucosa, Fonsecaea pedrosoi, Rhinocladiella aquaspersa, Fonsecaea compacta, and Cladophialophora carrionii. The infection is chronic and characterized by the slow development of progressive granulomatous lesions that in time induce hyperplasia of the epidermal tissue. Pathogenesis The fungi are introduced into the skin by trauma, often of the exposed legs or feet. Over months to years, the primary lesion becomes verrucous and wart-like with extension along the draining lymphatics. Cauliflower like nodules with crusting abscesses eventually cover the area. Small ulcerations or “black dots” of hemopurulent material are present on the warty surface. Rarely, elephantiasis, may result from secondary infection, obstruction, and fibrosis of lymph channels Epidemiology Chromoblastomycosis occurs mainly in the tropics. The fungi are saprophytic in nature, probably occurring on vegetation and in soil. The disease occurs chiefly on the legs of barefoot agrarian workers following traumatic introduction of the fungus. Chromoblastomycosis is not communicable. Wearing shoes and protecting the legs probably would prevent infection. PHAEOHYPHOMYCOSIS Phaeohyphomycosis is a term applied to infections characterized by the presence of darkly pigmented septate hyphae in tissue. Both cutaneous and systemic infections have been described. The clinical forms vary from solitary encapsulated cysts in the subcutaneous tissue to sinusitis to brain abscesses. Over 100 species of dematiaceous molds have been associated with various types of phaeohyphomycotic infections. They are all exogenous molds that normally exist in nature. Some of the more common causes of subcutaneous phaeohyphomycosis are Exophiala jeanselmei, Phialophora richardsiae, Bipolaris spicifera, and Wangiella dermatitidis. PHAEOHYPHOMYCOSIS In general, itraconazole or flucytosine is the drug of choice for subcutaneous phaeohyphomycosis. Brain abscesses are usually fatal, but when recognized they are managed with amphotericin B and surgery. The leading cause of cerebra phaeohyphomycosis is Cladophialophora bantiana What is Mycetoma? Mycetoma is a chronic granulomatous, progressive inflammatory disease that involves the subcutaneous tissue after a traumatic inoculation of the causative organism It may be caused by true fungi (eumycetes) or by higher bacteria (actinomycetes) and therefore it is classified into eumycetoma and actinomycetoma respectively Mycetoma This infection results in a granulomatous inflammatory response in the deep dermis and subcutaneous tissue, which can extend to the underlying bone Mycetoma is characterized by the formation of grains containing aggregates of the causative organisms that may be discharged onto the skin surface through multiple sinuses The disease was originally reported from Madurai, it is therefore commonly known as Maduramycosis or Madura foot It is seen mainly in tropics, though occasional cases have been reported from the temperate countries Madura foot Mycetoma Causative agents of eumycetoma Madurella mycetomatis Madurella grisea Exophiala jeanselmei Acremonium spp Aspergillus spp Fusarium spp Scedosporium (Pseudallescheria) Pathogenesis The causative agent is believed to enter through minor trauma. The disease usually begins as a small subcutaneous swelling of the foot, which enlarges, burrowing into the deeper tissues and tracking to the surface as multiple sinuses discharging viscid, seropurulent fluid containing granules. The lesions are painless. It may spread to involve deep structures resulting in destruction of bone, deformity and loss of function with serious social and economic implications. Lab diagnosis Demonstration of granules in the infected tissue The color and consistency of the granules vary with the different agents In actinomycotic mycetoma, the grains are composed of very thin filaments, while in mycotic lesions, they are broader and often show septae and chlamydospores Growth of organisms in culture and physiological and serological tests also help in establishing the diagnosis Treatment Surgery Antifungal therapy Amphotericin B Miconazole Ketoconazole Itraconazole Flucytosine Topical nystatin Topical potassium iodide (choice of treatment varies according to the infecting fungus) Rhinosporidiosis This is a chronic granulomatous disease characterized by the development of friable polyps, usually confined to the nose, mouth or eye but rarely seen on the genitalia or other mucous membranes Distribution Although the disease was first identified in Argentina, most cases come from India and Srilanka Rhinosporidiosis Causative agent: Rhinosporidium seeberi R. seeberi cannot be cultured in cell-free artificial media Animal inoculation is also not successful Pathogenesis and clinical features The mode of infection of this fungus is not known However, it is suggested that it is transmitted in dust and Rhinosporidium seeberi water Fish is believed to be the natural host of this fungus Infection is seen most commonly in persons taking bath in stagnant pools and in individuals who dive in streams to collect sand from river beds The disease is characterized by the development of large friable polyps or wart-like lesion in the nose, conjunctiva or eye The lesions can also be seen in buccal cavity, skin or genitalia Treatment Treatment of the condition is carried out by surgery or cauterization Chemotherapy with dapsone is also useful Laboratory diagnosis Specimens The samples to be collected include aspiration fluid, pus, biopsy material, skin scrapings and swabs Microscopy KOH (potassium hydroxide) mount of specimen or histopathological examination of tissue sections stained by methanamine silver stain Summary The fungi include diverse saprotrophic eukaryotic organisms with chitin cell walls Fungi can be unicellular or multicellular; some (like yeast) and fungal spores are microscopic, whereas some are large and conspicuous Reproductive types are important in distinguishing fungal groups Medically important species exist in the four fungal groups Zygomycota, Ascomycota, Basidiomycota, and Microsporidia Members of Zygomycota, Ascomycota, and Basidiomycota produce deadly toxins Important differences in fungal cells, such as ergosterols in fungal membranes, can be targets for antifungal medications, but similarities between human and fungal cells make it difficult to find targets for medications and these medications often have toxic adverse effects Reading