Fungal Biology Quiz: Ascomycota and Mycoses

Cutaneous and Subcutaneous Mycoses

• Mycology is the study of fungi
• Approximately 80,000 fungal species have been described, but fewer than 400 are medically important.
• Less than 50 species cause more than 90% of fungal infections
• Fungi are beneficial in breaking down and recycling organic matter
• Fungi contribute to food and beverages (cheese, bread, beer)
• Fungi produce bioactive secondary metabolites like antibiotics (penicillin) and immunosuppressants (cyclosporine)
• Fungi are eukaryotes, with a higher biological complexity than bacteria
• Fungal cells have a nucleus, nuclear membrane, endoplasmic reticulum, mitochondria, and a secretory apparatus
• Most fungi are obligate or facultative aerobes
• Fungi reproduce both sexually and asexually
• Some fungi are unicellular; others become multicellular via branching filaments
• Fungi absorb nutrients; they lack chlorophyll
• The fungal cell wall is different from bacteria and plant cells chemically
• The main sterol in fungi is ergosterol, while in mammals it is cholesterol
• Fungi are typically haploid, although diploid nuclei are formed during sexual reproduction
• Fungal cells are typically surrounded by a rigid cell wall
• The cell wall is made up of polysaccharides (mannan, glucan, and chitin) and structural proteins
• Fungal infections are termed mycoses
• Mycoses can be classified as superficial, cutaneous, subcutaneous, or systemic (Table 45-1)
• Systemic mycoses often exhibit subcutaneous manifestations and vice versa
• Most patients with opportunistic infections have compromised host defences

Fungal Structure

• Fungal cells have a nucleus, nucleolus, nuclear membrane, linear chromosomes, cytoskeleton (actin microfilaments and tubulin-containing microtubules), ribosomes, and other organelles (e.g., mitochondria, endoplasmic reticulum and Golgi apparatus)
• Fungal cells have a rigid cell wall (external to cytoplasm membrane).
• Fungi differ from bacterial and plant cells in their sterol composition/make up.

Yeasts and Molds

• Fungi grow as yeasts or molds
• Mold growth is by multicellular filamentous colonies
• Colonies are composed of branching cylindrical tubules called hyphae, with diameters from 2μm – 10μm
• Intertwined hyphae form a mycelium
• Hyphae may be divided into cells with cross-walls or septa (like compartments), appearing at regular intervals during growth
• Some medically significant molds, like zygomycetes, have hyphae that are not septated
• Other fungi have septate hyphae
• Aseptate (coenocytic) hyphae have multinucleated cytoplasm
• Fungi grow through the development of hyphae (like extensions of the cell)
• These extended hyphae form an interwoven mass referred to as the mycelium.
• A portion of the mycelium (vegetative mycelium) absorbs nutrients
• The aerial mycelium produces spores for reproduction
• Mycelium is like a root
• Aerial mycelium bears reproductive structures (conidia or spores)
• The hyphae are rigid to support the interwined network which is a mold

Types of Hyphae

• Vegetative hyphae penetrate the medium for nutrient absorption
• Aerial hyphae extend above the surface to provide support or to reproduce.
• Reproductive hyphae carry spores for reproduction.
• Mycelium is a collection of hyphae

Asexual Spores on Aerial Mycelia

• Sporangiospores develop in a sporangium on sporangiophore
• Conidia form on conidiophore, developing from the hyphae directly or on specialized structures
  • Arthrospores are conidia formed when the hyphae break down into septate segments
  • Chlamydospores are thick-walled spores produced within the hyphae
  • Blastospores are produced by budding
  • Phialospores are formed on the outside of specialized conidiophores
  • Macroconidia: Larger in size compared to microconidia
  • Microconidia: Smaller in size compared to macroconidia

Yeasts

• Yeasts are single cells, typically spherical or egg-shaped, with diameters of 3–15 μm.
• Yeasts reproduce via budding.
• Some yeasts produce buds that, rather than detaching, become elongated, producing a chain of elongated cells, called pseudohyphae.

Yeast vs. Hyphae

• Pseudohyphae differ from hyphae in recurring bud-like constructions and in being less rigid
• Yeasts colonize mucosal surfaces and spread to other locations (especially in immuncompromised hosts)
• Pseudohyphae have enhanced nutrient scavenging capabilities, and motility.
• Hyphae invade host tissues and breach endothelial cell layers. They are capable of lysing macrophages and neutrophils and exhibit thigmotropism and antigenic variation.

Reproduction

• Fungi reproduce sexually or asexually
• Asexual reproduction produces conidia, which arise either from condiophores or directly from existing hyphae
• Sexual reproduction produces ascospores

Spores

• Spores are readily dispersed
• Spores are resistant to harsh environments
• Spores can germinate when conditions for growth are favorable
• Spores can derive from asexual or sexual reproduction

Fungal Groups

• Fungi are classified into four phyla: Chytridiomycota, Zygomycota, Ascomycota, and Basidiomycota.
• Ascomycota includes more than 60% of known fungi and about 85% of human pathogenic fungi
• Zygomycota or Basidiomycota are the remaining pathogenic fungi

Zygomycota

• Sexual reproduction results in zygospores
• Asexual reproduction occurs via sporangia
• Vegetative hyphae are sparsely septate

Ascomycota

• Sexual reproduction involves a sac (ascus) where karyogamy and meiosis occur
• Asexual reproduction is via conidia
• Molds have septate hyphae.

Basidiomycota

• Sexual reproduction forms four basidiospores on a club-shaped basidium
• Hyphae are complex and septate.

Culturing

• Fungi readily grow on simple sources of nitrogen and carbohydrates.
• Sabouraud's agar is used because it doesn't support bacterial growth

Fungal Medical Significance

• Various fungi (yeasts, molds, and fleshy fungi) have medical, veterinary, or agricultural importance due to causing infections
• Fungal infections in humans, animals and plants are called mycoses

Grouping of Medically Important Fungi

• Grouping fungi by the tissues they parasitize and diseases produced
• Superficial fungi: dermatophytes (e.g., ringworm, athlete's foot)
• Subcutaneous fungi cause infections in the skin and extend to subcutaneous tissue (e.g., sporotrichosis, chromoblastomycosis, phaeohyphomycosis, mycetoma)
• Opportunistic fungi found in the environment or normally in the flora, producing disease in compromised situations
• Systemic fungi are highly virulent and cause progressive systemic diseases (e.g., histoplasmosis)

Superficial Mycoses

• Superficial mycoses involve infection of the outermost body areas (hair, nails and epidermis)

Pityriasis Versicolor

• A chronic superficial infection of the stratum corneum
• Caused by Malassezia globosa, M restricta, or other members of the M furfur complex
• Characterized by discrete, serpentine, hyper or hypopigmented maculae mainly on the back.
• Treated with selenium sulfide or azoles

Tinea Nigra

• A superficial, chronic, and asymptomatic infection of the stratum corneum
• Caused by Hortaea (Exophiala) werneckii
• Characterized by a dark-colored discoloration, often on the palms (especially in young women).
• Treated with keratolytics, salicylic acid, or azole antifungals

Piedra

• Nodular infections of hair shafts
• Black piedra is caused by Piedraia hortai
• White piedra is caused by Trichosporon species
• Treated by hair removal and topical antifungals.

Cutaneous Mycoses

• Cutaneous mycoses are fungal skin infections
• Caused by fungi that infect only superficial keratinized tissues (skin, hair, and nails)
• Dermatophytes are the most important ones of these (Microsporum, Trichophyton, Epidermophyton)

Dermatopytoses

• Dermatophytoses are among the most prevalent fungal infections
• The infections are not usually life-threatening but can be troublesome
• Acquired by contact with contaminated soil or infected animals/humans
• Geophilic, zoophilic, or anthropophilic, depending on whether the habitat is soil, animals or humans, respectively.

Epidemiology & Immunity

• Dermatophytes infections begin with trauma/contact
• Susceptibility may be enhanced by factors such as moisture, warmth, skin chemistry, youth, and heavy exposure
• The incidence is higher in hot/humid climates and crowded living conditions
• Transmission from soil/infected animal
• Trichophytin is a crude antigen preparation used to detect hypersensitivity

Tinea Pedis (Athlete's Foot)

• Usually occurs as a chronic infection of toe webs
• Other types include vesicular, ulcerative, and moccasin
• Itching between toes, small vesicles developing, thin fluid discharge, maceration and peeling, secondary bacterial infection
• Peeling/cracking are the principal manifestations, accompanied by pain and pruritus
• Chronic infections

Tinea Unguium (Onychomycosis)

• Nail infection following prolonged tinea pedis
• Manifestations: brittle, thickened, crumbly nails

Tinea Corporis, Tinea Cruris, and Tinea Manus

• Dermatophytosis affects glabrous skin
• Annular lesions (ringworm) with a clearing, scaly center and red advancing border.
• Usually in dry or vesicular form
• Fungal metabolites, enzymes, and antigens cause erythema/vesicle formation/pruritus
• Lesions expand outward
• Tinea cruris (jock itch), infects the groin, may spread to scrotum
• Tinea manus (hand ringworm), involves fingers/hands

Tinea Capitis and Tinea Barbae

• Tinea capitis (scalp ringworm), an infection of scalp/hair follicles
• Infection begins with hyphal invasion of the skin and subsequent spread down the keratinized wall of hair follicle
• Infection above hair root, causes dull gray circular patches with alopecia, scaling and itching.
• Tinea barbae involves the bearded region

Treatment (General)

• Treatment involves removal of infected and dead epithelial structures
• Topical antifungal chemicals or antibiotics are used
• The area should be kept dry, sources of infection avoided

Treatment (Specific)

• Scalp infections: griseofulvin for 4–6 weeks, but azoles, ketoconazole, itraconazole, and terbinafine are quite effective
• Tinea corporis, pedis: itraconazole, terbinafine; topical preparations (miconazole, tolnaftate, clotrimazole, for 2-4 weeks)

Subcutaneous Mycoses

• Fungi reside commonly in soil/vegetation
• Enter skin/subcutaneous tissue via trauma from contaminated material/material
• Lesions become granulomatous and slowly expand
• Extension via lymphatics; usually confined to subcutaneous tissue but can become systemic
• Sporotrichosis, chromoblastomycosis, phaeohyphomycosis, mycetoma, lobomycosis, rhinosporidiosis

Sporothrix schenckii

• Thermally dimorphic fungus
• Grows as mold (ambient temperatures), or budding yeast at 35-37 degrees Celsius in tissue or vitro
• Causative agent for sporotrichosis
• Associated with vegetation/plant materials
• Acquired through traumatic inoculation
• Chronic granulomatous infection with secondary spread to draining lymphatics and lymph nodes

Sporotrichosis

• Chronic infection of cutaneous, subcutaneous, lymphatic tissue
• Commonly seen in gardeners, forest workers, and manual laborers
• Causative agent is Sporothrix schenckii
• Found in soil, decaying woods, thorns, infected animals

Chromoblastomycosis

• Subcutaneous fungal infection caused by traumatic inoculation of certain dematiaceous fungi
• Fungal agents: Phialophora verrucosa, Fonsecaea pedrosoi, Rhinocladiella aquaspersa, Fonsecaea compacta, Cladophialophora carrionii
• Chronic with gradual development of granulomatous lesions

Phaeohyphomycosis

• Infections characterized by darkly pigmented septate hyphae
• Forms from various species of dematiaceous molds, typically exogenous
• Geographic distribution: tropical countries
• Can develop as solitary encapsulated cysts, sinusitis, brain abscesses,
• Treated with itraconazole or flucytosine; amphotericin B and surgery for brain abscesses

Mycetoma

• A chronic, granulomatous, progressive inflammatory disease of the subcutaneous tissue
• Causative agents: true fungi (eumycetes) or higher bacteria (actinomycetes)
• Characterized by the formation of grains that contain aggregates of causative organisms and drain through multiple sinuses

Madura Foot

• A type of mycetoma, originally reported from Madurai.
• Chronic infection draining through sinuses on the skin

Rhinosporidiosis

• Chronic granulomatous disease characterized by the development of friable polyps (usually in the nose, mouth, eyes, rarely genitalia, or other mucous membranes)
• Distribution mainly from India and Sri Lanka, although first identified in Argentina.
• Causative agent: Rhinosporidium seeberi (cannot be cultured) believed to be transmitted in dust or water, with fish as the likely natural host

Treatment (Specific, Mycetoma)

• Treatments for mycetoma, including surgery, antifungal therapy (amphotericin B, miconazole, ketoconazole, itraconazole, flucytosine), topical nystatin, and topical potassium iodide.

Laboratory Diagnosis

• Tissue samples, aspiration fluid, pus, biopsy material, skin scrapings, and swabs are collected
• KOH mounts of specimens or histopathological examination of tissue sections stained by methanamine silver stain are used
• Cultivating organisms in culture and physiological/serological tests to assist with diagnosis

Summary (Main Points)

• Fungi are diverse saprophytic eukaryotes with chitin cell walls
• Some fungi are unicellular and others multicellular; many fungal spores are microscopic, whilst some are large.
• Reproductive types are significant for fungal group identification
• Medically important fungi belong to Zygomycota, Ascomycota, Basidiomycota
• Members of certain groups produce deadly toxins
• Important differences in fungal cells, e.g., ergosterol, are targets for antifungal medications. Similarities between human/fungal cells pose difficulty in finding ideal targets.