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What are the 2 main differences between fungi and higher eukarytocis?
Fungal membranes contain ergosterol instead of cholesterol.
Fungi are surrounded by a rigid cell wall composed of carbohydrate polymers and protein
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What are the two morphologies of fungi?
Yeast: unicellular, reproduce by budding or fission (3-15 um)
Hyphae/Mycelium (mold): branching cylindric tubules varying in diameter (2-10 um)
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What are the 4 types of sexual spores?
- Zygospores: large thick-walled, formed by fusion at tips of two sexually compatible gametangia
- Ascospores: single-celled spores produced in an ascus, usually 4-8 per ascus.
- Basidiospores: single-celled spores located on a club-shaped structure
- Chyltridiomycetes: most primitive fungi, motile cells
- Deutromycetes: do not produce any known sexual spores
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What are the 5 asexual reproductive elements?
- Blastoconidia: budding
- Chlamydoconidia: thick walled single cells that are resistant to adverse conditions
- Arthroconidia: single celled conidia formed by disjoining hyphal cells
- Conidiospores: borne naked on specialized structures (macroconidia, microconidia)
- Sporangiospores: single-celled, formed w/in sacs at the end of a special hyphae
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What are some diagnostic laboratory procedures to identify fungal infections?
Direct microscopic examination (KOH technique, staining)
Cultivation on blood agar, Sabouraud's agar - must include antibiotics to inhibit bacterial growth
Serologic methods
PCR
FISH
Mass spectrometry
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What are some good combination therapy techniques?
- Inhibition of different stages of the same biochemical pathway (terbinafine and azoles)
- Increased penetration of one agent into the cell through a permeabilizing activity of another agent (amphotericin b/flucytosine)
- Inhibition of transport of one agent out of the cell by another agent (reserpine & azoles)
- Simultaneous inhibition of different fungal cell targets (caspofungin with amp. B or azoles)
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Which combo therapy produces antagonistic effects?
Azole depletes ergosterol which is a target for amphotericin B.
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Which fungi does not benefit from combo therapy?
Aspergillus
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How does resistance develop to antifungal drugs?
Fungi do not destroy or modify antifungal drugs.
Resistance occurs through efflux pumps, target alterations, reduced access to drug targets.
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What is the eagle effect?
Organism is resistant to high concentrations of the drug but susceptible to low concentrations.
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Malassezia furfur:
Lesion
Infection site
Disease
Additional information
Treatment
- Yeast (infrequent branched hyphae)
- Skin (pink to brown)
- Pityriasis (tinea) versicolor
- Wood's lamp yellowish - spaghetti&meatballs
- Local: azoles/selenium sulfide
- Widespread: oral azoles
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Hortaea weneckii/Expophilia werneckii
Disease
Morphology
Epidemiology
Clinical Syndromes
Lab Diagnosis
Tx
- Tinea nigra
- dermaticeaous (dark colored) frequently branched, septate hyphae
- black mold with annelloconidia
- tropical/subtropical regions - africa, asia, s. america
- contracted by inocculation into superficial layers of epidermis
- solitary, irregular, pigmented macule, usually on palms or soles - can resemble malignant melanoma
- infection not contagious
- direct microscopic visualization of fungal elements in KOH prep
- azoles/terbinafine
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Piedraia hortae
- Black piedra
- Brown-reddish-black mold w/ ascospores on cultures
- Latin america/central africa - poor hygiene
- Hard dark nodules surround hair shaft
- Tx: haircut, washing, topical antifungals
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Trichosporon inkin, asahii, mucoides
- White piedra
- Yeast-like
- Hyphal elements, arachronidia, blastoconidia
- Tropical/subtropical regions - poor hygiene
- Surrounds hair shaft and forms white-brown swelling- groin axillae
- Microscopic exam, culture w/o cyclohexamide - cream colored dry
- Tx: remove hair, improve hygiene, topical azoles
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What are the 3 dermatophytes and their morphology?
- trichophyton: numerous, spherical or teardrop/peg shaped micronidia - rare, smooth-thin walled macronidia
- epidermophyton: smooth walled, clusters of 2-3 macronidia, absent micronidia
- microsporum: numerous, large, thick, and rough walled macronidia, rare micronidia
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What is the morphology of dermatophytes?
hyaline septate hyphae, chains of arthroconidia and dissociated arthroconidia - restricted to nonviable skin b/c unable to grow at 37degrees or serum
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What are the ecological categories of dermatophytes and how do they respond to therapy?
Zoophilic/geophilic: elicit strong host response and respond well to therapy
Antrophilic: chronic infection, mild host response, difficult to cure
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What 2 fungi account for 80-90% of all dermatophytic infections?
Trichophyton rubrum & mentagrophytes
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Sporothrix schnecki
- subcutaneous mycoses
- lymphocuteanous sportrichosis
- traumatic induction through dermis
- soil & decaying matter
- thermally dimorphic
- warmer climates: Japan and Americas
- inoculation site is nonpainful - appears as nodular lesion that will ulcerate - series of linearl nodules can appear as it spreads through lymphatics
culture = definite dx
- Tx: oral KI in developing countries (adverse SE)
- itraconazole: safe effective, adminster 3-6 mos.
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