Term
Treatment for superficial mycoses |
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Definition
* Polyenes, azoles in creams
* Also griseofulvin, allylamines |
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Term
Treatment for systemic mycoses |
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Definition
* Polyenes azoles
* In combination with 5-flucytosine |
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Term
What type of local therapy can be used for vulvovaginal candidiasis? |
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Definition
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Term
Oral therapy is used for what type of mycoses |
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Definition
Skin and nail infections for up to one year |
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Term
Systemic mycoses are treated via what route? |
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Definition
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Term
Major chemical feature of polyenes |
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Definition
They are amphipathic and therefore capable of inserting into membranes |
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Term
What do polyenes primarily bind to? |
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Definition
Sterols with poor specificity, mainly ergosterol |
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Term
Polyene used for systemic fungal infections |
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Definition
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Term
Why are the polyenes toxic? |
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Definition
Cross-reaction with cholesterol in host cell |
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Term
How are the polyenes administered |
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Definition
Chiefly IV because of poor absorption; can be given p.o. to treat GI infections |
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Term
Polyene used for topical treatment of superficial dermatophytoses, including oral and intestinal Candida infections |
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Definition
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Term
Adverse reactions of systemic polyene administration |
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Definition
* Fever
* Nephrotoxicity
* Hypokalemia (cardiotoxicity) |
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Term
Less toxic form of polyenes |
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Definition
Lipid formulations of amphotericin B |
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|
Term
How polyenes disrupt fungal membranes |
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Definition
Multiple polyenes bind, form pore and cause lysis |
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Term
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Definition
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Term
T/F: Most antifungal therapy uses amphipathic drugs |
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Definition
True (polyenes are amphipathic) |
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Term
Are most antifungals fungocidal or -static? |
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Definition
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Term
Mechanism of action of azoles |
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Definition
Inhibit synthesis of ergosterol |
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Term
Clinical uses of ketoconazole |
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Definition
* Systemic and mucocutaneous infections
* Prevention of Candida infection in immunocompromised |
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Term
Is ketoconazole good against cryptococcal meningitis? |
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Definition
No because it doesn't get into CNS well |
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Term
Adverse reactions of ketoconazole |
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Definition
* GI distress
* Hepatotoxicity
* Steroid synthesis inhibition |
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Term
Why fluconazole is less toxic to humans |
|
Definition
Less active against mammalian cytochrome P450 |
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Term
Relative antifungal spectra of ketoconazole, fluconazole, and itraconazole |
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Definition
Itraconazole > fluconazole > ketoconazole |
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Term
|
Definition
* Many CYP interactions
* Hepatotoxicity |
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|
Term
Topically tend to be imidazole or triazoles? |
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Definition
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|
Term
Biggest concern of azole administration |
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Definition
Resistance, which is why 3rd generation of azoles were created |
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Term
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Definition
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Term
Drugs that inhibit squalene epoxidase |
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Definition
Allylamines (eg, terbinafine) |
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|
Term
Consequences of squalene epoxidase inhibition |
|
Definition
* Buildup of intracellular squaline (fungotoxic)
* Decreased ergosterol synthesis |
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Term
Adverse reactions to terbinafine |
|
Definition
* GI distress
* Taste disturbances
* Hepatotoxicity |
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|
Term
Therapeutic niche for terbinafine |
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Definition
* Tinea cruris
* Tinea corporis |
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Term
General class of antifungals associated with cell wall synthesis inhibition |
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Definition
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Term
Antifungal that inhibits beta-(1,3)-glucan synthase |
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Definition
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Term
Fungal targets of caspofungin |
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Definition
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Term
Adverse reactions of caspofungin |
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Definition
* Nausea
* Vomiting
* Fever
* Phlebitis |
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|
Term
Inhibitor of beta-(1,3)-glucan synthase |
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Definition
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Term
Mechanism of action of flucytosine and fluorouracil |
|
Definition
Inhibition of DNA and RNA synthesis |
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Term
Caspofungin inhibits a beta-(1,3)-glucan synthase that is active during what stage of fungal growth? |
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Definition
During formation of bud (thus very effective against yeast cells while not great against filamentous except for Aspergillus) |
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Term
Why caspofungin might be less effective against hyphal organisms than budding organisms |
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Definition
* Hyphae generally more stable
* Don't form cell wall septa |
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|
Term
Are flucytosine and fluorouracil effective if administered alone? |
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Definition
No, because of side effects |
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Term
Fluorouracil is an inhibitor of what stages of metabolism? |
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Definition
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|
Term
Active form of 5-flucytosine |
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Definition
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Term
Antifungals that interacts with polymerized microtubules and keratin |
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Definition
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Term
Mechanism of mitosis inhibition of griseofulvin |
|
Definition
Disrupt mitotic spindle by binding polymerized microtubules |
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|
Term
Side effects of griseoflvin |
|
Definition
* Transient headache
* Mental confusion, fatigue, visual impairment
* GI distress |
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|
Term
Niche uses of griseofulvin |
|
Definition
Superficial dermatophytes
* Trichophyton
* Epidermophyton
* Microsporum |
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Term
|
Definition
* Allergy
* Toxins
* Destroy tissue (mycosis) |
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Term
Morphology of most pathogenic fungi |
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Definition
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Term
How do fungi get their nutrients? |
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Definition
Feed on dead or decaying tissue (hence saprophytic) |
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|
Term
Three locations of fungal infections |
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Definition
* Superficial
* Subcutaneous
* Systemic |
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Term
Fungal species associated with lung and meningeal infections |
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Definition
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|
Term
Fungal species associated with oral and GI tract infections |
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Definition
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|
Term
Fungal species associated with subcutaneous infection of the arms and hands |
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Definition
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|
Term
Fungal species that causes Athlete's foot (superficial infection of skin and between toes) |
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Definition
* Epidermophyton
* Trichophyton |
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Term
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Definition
Can be haploid or diploid |
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|
Term
Fungal cell wall components |
|
Definition
* Chitin
* Glycoproteins (mannans, glucans) |
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|
Term
Monomeric subunit of chitin |
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Definition
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|
Term
Are fungi autotrophs or heterotrophs? |
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Definition
Heterotrophs, specifically saprophytes (live on dead organic matter) |
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Term
How do fungi obtain nutrients? |
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Definition
Secrete degradative enzymes (proteases, lipases, glucanases, etc.) into immediate invironment |
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Term
|
Definition
Moist environment (soil, water) containing decaying organic matter |
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Term
Morphological transition required for virulence in C. albicans |
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Definition
Budded-to-hyphal transtion |
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Term
Fungal morphology associated with filamentous growth of cells with well defined borders |
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Definition
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|
Term
Fungal morphology associated with filamentous growth of cells whose borders are not easily discerned |
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Definition
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Term
Do both fungi and bacteria have sterols in their cell membranes? |
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Definition
No, only fungi (and other eukaryotes) have sterols. (Mycoplasma is the one bacterial species that violates this rule; it does have sterols in its cell membrane.) |
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Term
Do fungi have generally have endo- and exotoxins? |
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Definition
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Term
Saccharomyces cerevisiae and Neurospora crassa exist vegetatively in a haploid or diploid state? |
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Definition
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|
Term
Are ascospores similar to bacterial endospores? |
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Definition
No; ascospores are sexual spores intended for fungal reproduction, while endospores are intracellular spores that provide protection. |
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Term
Another name for meiosis in fungi |
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Definition
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Term
How does Saccharomyces cerevisiae generate zygotes? |
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Definition
Haploid ascospores of the a and alpha variety join together |
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Term
Primary method by which filamentous fungi reproduce and spread within the environment |
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Definition
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Term
Structure responsible for fungal color as seen on food |
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Definition
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Term
How are conidia and ascospores developed? |
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Definition
* Conidia: asexually (mitosis of a haploid cell)
* Ascospores: sexually (meiosis of a diploid cell) |
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Term
What type of spore is often used to identify fungal species? |
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Definition
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|
Term
Species of what two fungal genera cannot be discerned under the microscope? |
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Definition
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Term
Non-culture methods using antigens are useful for differentiating between species of what two fungal genera? |
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Definition
* Cryptococcus
* Histoplasma |
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|
Term
Dye used to stain conidia |
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Definition
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|
Term
How is a 10% KOH solution useful for identifying fungal infections? |
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Definition
Solution dissolves mammalian tissue to isolate fungal cells |
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|
Term
Stains used histologically to stain fungi pink or black |
|
Definition
* Pink: Periodic acid Schiff (PAS)
* Gomori's methenamine silver (GMS) |
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|
Term
Spherules visible on microscopy is suggestive of a fungal infection by what organism? |
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Definition
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|
Term
Typical immune response to fungi |
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Definition
Cell-mediated (humoral response isn't useful) |
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|
Term
Why Candida albicans is so frequently seen in nosocomial infections |
|
Definition
It's a commensal organism |
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|
Term
Between 1980 and 1990, the frequency of what type of fungal infection increased the most? |
|
Definition
Bloodstream infections (400%) |
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|
Term
Fungi capable of avoiding clearance in the lungs |
|
Definition
* Aspergillus
* Cryptococcus
* Histoplasma |
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|
Term
C. albicans must grow in what form in order to penetrate epithelium? |
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Definition
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|
Term
Does auxotrophy make an organism more, or less virulent? |
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Definition
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|
Term
Fungal goals achieved by fungus-mediated host tissue necrosis |
|
Definition
* Overcomes tissue barriers
* Provides nutrients for fungus |
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|
Term
Deletion of what protease genes can cause attenuated virulence in C. albicans? |
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Definition
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|
Term
Two mechanisms by which C. albicans can cross epithelial barriers? |
|
Definition
* Induced phagocytosis (like Salmonella)
* Hyphal penetration |
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|
Term
What fungal organisms require a budded-hyphal transition for virulence? |
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Definition
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|
Term
What fungal species can grow as yeast or hyphae? |
|
Definition
* Blastomyces
* Candida
* Histoplasma |
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|
Term
Once C. albicans reaches the blood, what form does it assume? |
|
Definition
Budded form (following a hyphal-to-budded transition) |
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|
Term
|
Definition
Multinucleate cells containing hundreds of Coccidioides endospores |
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|
Term
During what phase of growth do Coccidioides form spherules? |
|
Definition
Saprophytic phase (a form of hyphal growth) |
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|
Term
Fungi that secrete phospholipases targeting the host cell membrane |
|
Definition
* Aspergillus
* Candida
* Cryptococcus |
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|
Term
Unique characteristics of Candida and Histoplasma required for virulence |
|
Definition
Budded-to-hyphal transition |
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|
Term
Fungi that can degrade cell membranes with phospholipases |
|
Definition
* Aspergillus
* Candida
* Cryptococcus |
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