Mycology

Question 1

Fungal capsule

Answer 1

Only present in some yeasts

-Consists of polysaccharide structure
-Function as virulence factor -adhesion; and phagocytic evasion

Cryptococcus neoformans (encapsulated yeast)

Question 2

Fungal cell wall (molecular composition)

Answer 2

Multilayered containing polysaccharides (~90%): polyhexoses, or polyhexosamines

Polysaccharides include different combinations of chitin, chitosan, cellulose, alpha-glucans, beta-glycans, and mannan

Question 3

Fungal cell membrane

Answer 3

Has phospholipid bilayer that contains sterols (ergosterol, zymosterol)

Question 4

Ergosterol

Answer 4

Major sterol in some fungi that is a target for drugs - the synthesis pathway makes a good target (not made in humans)

Question 5

Fungal dimorphism

Answer 5

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

Question 6

Two modes of fungal sexual reproduction

Answer 6

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

Question 7

Dermatophytes

Answer 7

Cutaneous fungal infection in the living layer of the epidermis - may involve inflammation

Etiological agenst are called dermatophytes

Question 8

Typical portal of entry for systemic fungal infection

Answer 8

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

Question 9

Fungal spores

Answer 9

1. Conidia
2. Sporangiospores

Question 10

Fungal asexual reproduction

Answer 10

1. Fragmentation of hypae
2. Budding
3. Spores

Question 11

Fragmentation of hypae

Answer 11

Asexual reproduction

Vegetative hyphae breaks up into individual cells

Question 12

Polyenes

Answer 12

Target the fungal cell membrane - target ergosterol - creates holes in membrane

Fungicidal drugs

Nystatin and amphotericin B

Question 13

Nystatin

Answer 13

Polyene

Primarily used for treating superficial fungal infections

i.e. thrush or skin infections

Applied topically

Only effective against Candida

Question 14

Amphotericin B

Answer 14

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)

Question 15

Azoles

MOA

Answer 15

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)

Question 16

Ketoconazole

Answer 16

Inhibits human 11-beta-hydroxylase - decreasing steroid production (including testosterone)

Question 17

DOC to Tx and prevent cryptococcal meningitis

Answer 17

Fluconazole

Also used for Candida infections and prophylaxis in high-risk Pt’s

Question 18

Azole used to Tx life-threatening infections like aspergillosis and blastomycosis

Answer 18

Itraconazole - requires acidic environment for absorption

Sometimes used to Tx onychomycosis

Question 19

First-line Tx for invasive aspergillosis

Answer 19

Voriconazole

Can cause visual disturbances

Question 20

Echinocandins

Answer 20

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

1. Caspofungin
2. Micafungin
3. Anidulafungin

Not processed by liver or kidneys-no drug interactions/toxicity

Question 21

Micafungin

Answer 21

Can cause serious allergic reactions and also lead to hemolysis and elevated bilirubin

Echinocandin

Question 22

Anidulafungin

Answer 22

Effective against azole-resistant Candida (i.e.Candida albicans, Candida krusei, and Candida glabrata)

Echinocandin

Question 23

Flucytosine

Answer 23

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)

Question 24

Griseofulvin

Answer 24

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

Question 25

Terbinafine

Answer 25

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) ## Footnote Is hepatotoxic

Question 26

Cyclopirox

Answer 26

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

Question 27

Answer 27

C. Nystatin

Question 28

Answer 28

B. Terbinafine

Question 29

Answer 29

D. Any or all

Question 30

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:

Answer 30

Dimorphic fungi ## Footnote Dimorphic fungi are frank pathogens

Question 31

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"?

Answer 31

Arthrospores

Question 32

Approximately 1.4 billion people worldwide are current infected with intestinal roundworms. Roundworms are classified as which type of human parasite?

Answer 32

Nematode

Question 33

The spectrum of which of the following drugs is limited to Candida and Aspergillus infections? A. Amphoteracin B B. Caspofungin C. Fluconazole D. Itraconazole

Answer 33

B. Caspofungin

Question 34

What is the target enzyme of terbinafine?

Answer 34

Squalene epoxidase

Question 35

Answer 35

D. Amphotericin B and fluconazole

Question 36

Answer 36

D. Fluconazole ## Footnote Nystatin is only available as a powder or cream

Question 37

Answer 37

D. Changes in a gene encoding for a fungal cytochrome P-450 enzyme ## Footnote 14-alpha-demethylase is a fungal P450 enzyme All azoles are fungistatic not fungicidal

Question 38

Answer 38

B. Caspofungin ## Footnote Griseofulvin is only for dermatophyte infections (i.e. tinea)

Question 39

Answer 39

B. Voriconazole ## Footnote Terbinafine - squalene oxidase inhibitor only used to Tx dermatophyte infections

Question 40

Answer 40

D. It inhibits demethylation of lanosterol | Azole drugs demethylate lanosterol

Question 41

# Fungal sexual reproduction Keryogamy

Answer 41

Nuclear fusion and subsequent meiosis

Question 42

# Fungal sexual reproduction Plasmogamy

Answer 42

Cell fusion during sexual reproduction