Mycology Flashcards
Fungal capsule
Only present in some yeasts
-Consists of polysaccharide structure
-Function as virulence factor -adhesion; and phagocytic evasion
Cryptococcus neoformans (encapsulated yeast)
Fungal cell wall (molecular composition)
Multilayered containing polysaccharides (~90%): polyhexoses, or polyhexosamines
Polysaccharides include different combinations of chitin, chitosan, cellulose, alpha-glucans, beta-glycans, and mannan
Fungal cell membrane
Has phospholipid bilayer that contains sterols (ergosterol, zymosterol)
Ergosterol
Major sterol in some fungi that is a target for drugs - the synthesis pathway makes a good target (not made in humans)
Fungal dimorphism
Some fungi can grow as either yeast-like or mold-like (depends on environmental conditions such as substrate, temperature, pH…etc.)
Dimorphic fungi are true, frank pathogens - immune system does not need to be supressed to become infected
Two modes of fungal sexual reproduction
Homothallic: haploid nuclei form adjoining parts of the same mycelium (thallus) resulting in an oospore
Heterothallic: thalli of different “mating strains” fuse, allowing haploid nuclei from two strains to fuse and form a zygospore
Dermatophytes
Cutaneous fungal infection in the living layer of the epidermis - may involve inflammation
Etiological agenst are called dermatophytes
Typical portal of entry for systemic fungal infection
Usually the respiratory tract (inhalation, usually spores) - initial lesions typically occurs in the lung - may progress slowly resulting in suppurative lesions or granuloma
Man-to-man transmission is rare
Metastatic lesions mayu occur in any organ or in the skin due to escape of organisms from primary lesion via the lymphatics or blood
Fungal spores
- Conidia
- Sporangiospores
Fungal asexual reproduction
- Fragmentation of hypae
- Budding
- Spores
Fragmentation of hypae
Asexual reproduction
Vegetative hyphae breaks up into individual cells
Polyenes
Target the fungal cell membrane - target ergosterol - creates holes in membrane
Fungicidal drugs
Nystatin and amphotericin B
Nystatin
Polyene
Primarily used for treating superficial fungal infections
i.e. thrush or skin infections
Applied topically
Only effective against Candida
Amphotericin B
Broad-spectrum
Used for systemic fungal infections and administered IV or intrathecally (spinal fluid)
Tx’s
Candida
Cryptococcus
and fungi responsible for:
blastomycosis
histoplasmosis
coccidoidomycosis
aspergillosis
Eliminated by liver and has a long half-life
Significant toxicity - liver disease, renal failure (in 80%), hypokalemia, phlebitis, cardiac arrest, seizures, dysrhythmias, intraslveolar hemorrhage, blood dyscrasias (agranulcytosis, leukopenia, thrombocytopenia)
Azoles
MOA
Inhibit 14-alpha-demethylase (fungal version of cytochrome P450’s)
The enzyme is necessary for converting lanosterol into ergosterol
All azoles are potent inhibitors of CYP450 enzymes - can lead to serious drug interactions (ketoconozole - known for causing fatal liver necrosis in rare cases)
Ketoconazole
Inhibits human 11-beta-hydroxylase - decreasing steroid production (including testosterone)
DOC to Tx and prevent cryptococcal meningitis
Fluconazole
Also used for Candida infections and prophylaxis in high-risk Pt’s
Azole used to Tx life-threatening infections like aspergillosis and blastomycosis
Itraconazole - requires acidic environment for absorption
Sometimes used to Tx onychomycosis
First-line Tx for invasive aspergillosis
Voriconazole
Can cause visual disturbances
Echinocandins
Work by inhibiting the synthesis of beta-1,3-D-glucan (essential component of fungal cell wall)
Given IV and only used to Tx infections caused by Candida and Aspergillus
- Caspofungin
- Micafungin
- Anidulafungin
Not processed by liver or kidneys-no drug interactions/toxicity
Micafungin
Can cause serious allergic reactions and also lead to hemolysis and elevated bilirubin
Echinocandin
Anidulafungin
Effective against azole-resistant Candida (i.e.Candida albicans, Candida krusei, and Candida glabrata)
Echinocandin
Flucytosine
MOA: converted to fluorouracil by cytosine deaminase (humans don’t have) and interferes with RNA and protein synthesis by competing w/ uracil
Only combined w/ other drugs (amphotericin B or itraconazole) to Tx serious fungal infections caused by Candida or Cryptococcus
Fungal infections of CNS
Fungistatic
Side-effects: bone marrow supression and liver toxicity (fluorouracil is used as a chemotherapy drug)
Griseofulvin
MOA: blocks microtubule assembly - preventing fungi from undergoing mitosis
Used to Tx dermatophyte infections such as ringworm
Reduces effectiveness of warfarin and oral contraceptives by inducing some CYP450 enzymes
Fungistatic
Side-effects: angioneurotic edema, GI bleed, and liver toxicity
Terbinafine
MOA: blocks squalene epoxidase (involved in early step - coversion of squalene to lanesterol - of ergosterol synthesis)
Taken orally fo 12 wks. to Tx nail fungus (dermatophyte infections)
Is hepatotoxic
Cyclopirox
MOA: chelates metal ions (inhibting enzymes that help break down peroxides)
Applied topically for nail fungus (typically lasting 12 months)
Fungostatic or -cidal depending on the organism
C. Nystatin
B. Terbinafine
D. Any or all
Some fungi that cause human disease can exist in two different forms. At ambient temperature, they exist as mold-like elements with spores that can become airborne. At body temperature, they transform into yeast-like elements, which can disseminate throughout the body. Fungi with this ability are called:
Dimorphic fungi
Dimorphic fungi are frank pathogens
During asexual replication, hyphal elements form “spores” from which a new fungal hyphae can be derived. Which type of spore is formed within the line of hyphal elements and is “barrel-shaped”?
Arthrospores
Approximately 1.4 billion people worldwide are current infected with intestinal roundworms. Roundworms are classified as which type of human parasite?
Nematode
The spectrum of which of the following drugs is limited to Candida and Aspergillus infections?
A. Amphoteracin B
B. Caspofungin
C. Fluconazole
D. Itraconazole
B. Caspofungin
What is the target enzyme of terbinafine?
Squalene epoxidase
D. Amphotericin B and fluconazole
D. Fluconazole
Nystatin is only available as a powder or cream
D. Changes in a gene encoding for a fungal cytochrome P-450 enzyme
14-alpha-demethylase is a fungal P450 enzyme
All azoles are fungistatic not fungicidal
B. Caspofungin
Griseofulvin is only for dermatophyte infections (i.e. tinea)
B. Voriconazole
Terbinafine - squalene oxidase inhibitor only used to Tx dermatophyte infections
D. It inhibits demethylation of lanosterol
Azole drugs demethylate lanosterol
Fungal sexual reproduction
Keryogamy
Nuclear fusion and subsequent meiosis
Fungal sexual reproduction
Plasmogamy
Cell fusion during sexual reproduction