Fungi Flashcards
What is a fungi?
Eukaryotic, heterotroph, often saphrophytic
Yeast
Single cell, spherical or elliptical, reproduce asexually by budding
Budding produces what?
Conidia
Molds
Multicellular, form thread-like filaments call hypae
Mycellium
Mass of hyphae
Dimporphic fungi
Mold-cold environment, yeast-warm environment
What do fungi produce through sexual reproduction?
Spores
Hyphae filaments
Grow toward nutrients, can facilitate invasion
Haustoria
Hyphae on parasitic fungi
What is important issue when treating eukaryotic fungi?
Selective toxicity
What are good targets for antifungal medications?
Cell walls–cotain chitin and glucans. Ergosterol in plasma membrane (may have some toxicity…similar to cholesterol)
Polyenes
Amphotericin B and Nystatin
Mechanism of polyenes
Binds ergosterol, creates holes in membrane, allow for leaking of electrolytes, bactericidal
Spectrum of polyenes
Broad. Used for invasive systemic fungal infections in immunocompromised patients. Active against yeast and molds
Polyene distribution
Small fraction of drug excreted, long tissue half life. Liposomal form can cross blood brain barrier!!!
Polyene adverse effects
Nystatin treats Candida topically. Toxic because it is able to bind cholesterol! Decreases renal blood flow, can cause permanent destruction of basement membrane, up to 80% of patients have nephrotoxicity!
Polyene resistance
Rare, decrease ergosterol in membrane
Azoles
Fluconazole, Itraconazole, Ketoconazole
Azoles mechanism
binds fungal P-450 enzyme (Erg11), blocking production of ergosterol and causing accumulation of lanosterol, fungistatic
Azoles spectrum
Most widely used antifungal, spectrum varies by agents
Azoles distribution
Orally available through cola/acid (helps facilitate absorption of itraconazole and ketoconazole)
Azoles toxicity
Drug-drug interactions, hepatotoxicity, neurotoxicity, alters hormone synthesis. Avoid during pregnancy!!!
Azoles resistance
Altered cytochrome P-450, upregulation of efflux transporters
Allylamines
Terbinafine (Lamisil)
Allylamines mechanism
Fungicidal, inhibits squalene epoxidase, leads to toxic accumulation of squalene
Allylamines spectrum
Dermatophytes
Allylamines toxicity
Topical, drug interactions with CYP2D6 substrates
Allylamines resistance
Rare in human pathogens but could include decreased uptake, mutant binding site, and substrate for efflux transporters
Flucytosine (5-FC) mechanism
Nucleic acid synthesis inhibitor. Antimetabolite secectively taken up and converted to 5-flurouracil in fungi, interfering with DNA and RNA synthesis. Fungistatic
Flucytosine spectrum
Narrow-yeast. Candida albicans and cryptococcus
Flucytosine distribution
Oral, penetrates the CNS
Flucytosine toxicity
Only partially selective for yeast, can lead to bone marrow suppression, follow patient’s cell count carefully
Flucytosine resistance
Loss of converting enzyme or transporters, rarely used as monotherapy. Often cotreat with amphotericin B to increase uptake and minimize the likelihood of developing resistance
Griseofulvin mechanism
Binds microtubules, inhibits spindle leading to multinucleate cells, fungistatic
Griseofulvin spectrum
Dermatophytes
Griseofulvin distribution
Lipids increase oral absorption and then concentrates in dead keratinized layer of the skin
Griseofulvin toxicity
Teratogenic. Do NOT use if pregnant!!!
Griseofulvin resistance
Change to beta-tubulin, need to take orally for months and if patient not compliant, resistance mutations more likely to occur
Echinocandins (caspofungin) mechanism
Cell wall inhibitor blocks synthesis of beta (1,3)-d-glucan polysaccharide. Fungicidal for candida, fungistatic for aspergillus
Echinocandins (caspofungin) spectrum
Candida albicans, system
Echinocandins (caspofungin) distribution
IV, large molecular weight prohibits CNS penetration
Echinocandins (caspofungin) toxicity
Limited, fever, rash at site of infection
Echinocandins (caspofungin) resistance
Change in (1,3) beta D-glucan synthase gene
What percentage of spores are capable of initiating fungal infection?
0.1%. Begins in lungs or on skin
Mtcotoxicoses
Poisoning from toxins made by a fungus
Mycosis
Fungus grows on or in the individual
How rapidly do fungal infections develop?
Very slowly unless individual has suppressed immune system
Cutaneous fungal infections
Malassezia (tinea versicolor)
Dermatophytes-microsporum, epidermophyton, trichophyton
Subcutaneous fungal infections
Infection through skin, followed by subcutaneous or lymphatic spread (ex. Sporothrix)
Opportunistic mycoses
Candida albicans part of normal flora. Infections in patients with immune deficiencies
Diagnosis of fungal skin infection
Collect skin, hair, or nail with scraping. 10% KOH, can add stain, view under microscope. Some fungi fluoresce under Wood’ lamp (UV-A), can also do PCR or culture
