Fungi

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Fungi: human pathogens overview

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Mostly Deuteromycetes
-no sex
-eukaryotes: nucleus, mitochondria, ER, vacuoles, NO choroplasts, cell membrane, rigid cell wall (chitin, glucan)

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anti-fungal drugs target

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ergosterol in the fungal cell membrane

Polyenes: Amphotericin B
-Form a complex with ergosterol in plasma membrane

Imidazole and triazole derivatives
-Inhibit synthesis of ergosterol
-Imidazoles usually topical: clotrimazole, miconazole
-Triazoles more soluble, given orally: fluconazole, itraconazole

Allylamines
-Inhibit synthesis of ergosterol, different enzyme from azoles
-Example terbinafine (Lamisil)

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Morphological Classification Of Fungi

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Yeast - Unicellular, reproduce by budding or fission

Mold - Multicellular, composed of hyphae, other specialized structures

Dimorphic - Yeast or mold under different growth conditions [e.g. thermal dimorphism - many human pathogens are yeasts at 37C but molds at room temp]

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Specialized Structures of Molds: Hyphae

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Hyphae (sing. Hypha) - tubular structural units of molds (4-6mm diam).
-Contain cytoplasm and organelles. Some may have cross walls (septate) others do not (non-septate).
-Hyaline (transparent) vs. dematiaceous (dark pigmented)
-Specialized hyphae: conidiophores, sporangiophores, rhizoids (roots), etc.
Mycelium - a mass of hyphae that form a visible colony

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Specialized Structures: Spores

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1. Microconidia - small spores, unicellular

2. Macroconidia - large spores, multicellular

3. Sporangiospores - spores in a sack (sporangium)

4. Blastospores - buds on a yeast cell

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Fungal syndromes that are
NOT infectious diseases

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Fungal allergy – hypersensitivity to spores, hyphae, metabolites, etc.
-allergic rhinitis, asthma, hypersensitivity
pneumonitis

Fungal toxicoses – usually ingestion of contaminated food, occasionally inhalation of volatile toxins
-Ergotism – contaminated rye products induce hallucinations, convulsive symptoms, gangrenous lesions
-Aflatoxins – contaminate many cereal, seeds, nuts. Can cause liver damage, cancer
-“Black mold” – respiratory and other symptoms thought to be due to volatile toxic metabolites (controversial)

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Fungal Diseases of the Skin

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Superficial mycoses
-Pityriasis (tinea) versicolor
-Caused by: Malassezia furfur

Cutaneous mycoses (Dermatophytoses)
-Tinea capitis (ringworm of the scalp)
-Tinea corporis (ringworm of the body)
-Tinea barbae ("barber's itch")
-Tinea cruris ("jock itch")
-Tinea pedis ("athlete's foot")
-Tinea unguium (onychomycosis)
-Caused by: Microsporum, Epidermophyton, Trichopyton

Subcutaneous mycoses:
-Sporotrichosis (caused by Sporothrix schenckii)
-Chromoblastomycosis (caused by Fonsecaea, Cladosporium, Phialophora)
-Mycetoma (eumycotic mycetoma) (caused by Madurella, Acremonium, Aspergillus)

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Pathogenesis of Dermatophytoses

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Caused by many different organisms. Can be acquired from:
-soil (“geophilic”)
-animals (“zoophilic ”)
-humans (“anthropophilic”)

Pathogenesis
-colonization of keratinized, nonliving layers of skin
-organisms produce keratinase
-Inflammation leads to symptoms, e.g., itching

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Diagnosis and Treatment of Dermatophytoses

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Diagnosis: observe mycelia in skin scrapings - “KOH prep”

Treatment:
-Topical antifungals - exception is tinea unguium (poor access)
-Prolonged treatment after symptoms disappear

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Systemic Mycoses

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Histoplasmosis caused by Histoplasma capsulatum

Blastomycosis caused by Blastomyces dermititidis

Coccidioidomycosis caused by Coccidioides immitis

Cryptococcosis caused by Cryptococcus neoformans

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Systemic Mycoses: Histoplasmosis,
Blastomycosis, Coccidioidomycosis
Pathogenesis and dimorphism and treatment

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Pathogenesis:
-Acquired by inhalation of spores, esp. from bird or bat droppings. No human-to-human transmission.
-Occasionally acute, usually chronically progressive lung disease, similar to tuberculosis
-May spread systemically to form cutaneous lesions and infect joints, meninges, other organs
Dimorphism
-Yeast cells visible in tissues.
-Mycelial (mold) state when cultured
Systemic antifungals

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Systemic Mycoses: Histoplasmosis,
Blastomycosis, Coccidioidomycosis
Geographical distribution

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Geographical Distribution:
-Blastomyces: Southeastern and South Central U.S.: Ohio and Mississippi River valleys
-Histoplasma: Central U.S.: Mississippi, Missouri, and Ohio River valleys
-Coccidioides: Southwestern U.S., esp. San Joaquin valley of CA (“Valley fever”)

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Dimorphism: Blastomyces, Histoplasma, Coccioides

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Blastomyces:
-Tissue: yeast shells
-Culture: mycelium with lollipop-like microconidia

Histoplasma:
-Tissue: Yeast
-Culture: "tuberculate macroconidia" or "ship's wheel shaped"

Coccioides:
-Tissue: Spherules (sporangia) with endospores)
-Culture: "Barrel-shaped" arthrospores alternate with hyphae

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Opportunistic Infections: Yeasts

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Cryptococcus neoformans
Acquired by inhalation of spores: -Pulmonary infection is subclinical
-Dissemination to CNS: Cryptococcal meningitis
-Yeasts are encapsulated, visible in India ink prep

Candida sp. (esp. C. albicans)
-Usually part of normal flora.
-Disease in “healthy” people due to impaired barrier function: Oral (“thrush”), vaginal, gastrointestinal
-Very common in AIDS and cancer patients. Can spread systemically: meningitis, endocarditis, others

Pneumocystis carinii (P. jiroveci)
-Acquired in childhood, lifelong colonization
-Causes disease primarily in immunosuppressed, especially AIDS patients: Pneumocystis carinii pneumonia (PCP)
-Formerly thought to be a protozoan parasite, but DNA sequencing places it in the fungal kingdom.

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Opportunistic Infections: Molds

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Aspergillus sp.
-Colonization of body cavities and surrounding tissues
-Invasive granulomatous and necrotizing lung infections
-Disseminated systemic disease
Zygomycetes (Mucor, Rhizopus, Absidia sp.)
-Rhino-facial-cranial involvement.
-Rapidly progressing necrotizing lesions
Other fungi, e.g., other Deuteromycetes

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Frequency of Opportunistic
Fungal Infections

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AIDS patients
-Pneumocystis 53%
-Candida 25%
-Cryptococcus 8%

Cancer patients
-Death in 30% leukemia, 15% lymphoma, 5% solid tumor
-Candida, Aspergillus