Fungus 1

Question 1

defining properties of fungi

Answer 1

• eukaryotic-80s ribosomes
• cell wall of chitin and beta glucan-no anti peptidoglycan antibiotics or enzymes
• cell membrane contains ergosterol instead of cholesterol-vulnerable to amphotericin B and azole drugs
• some are obligate aerobes, non are obligate anaerobes
• require preformed organic carbon nutrient source-heterotrophs
• most are environmental-except C albicans
• little person to person, little selective pressure for drug resistance, no eradication
• can grow in colder, drier, more acidic and higher osmotic pressure environments than bacteria-more superficial/cutaneous infections

Question 2

yeasts

Answer 2

single cells

-reproduce by budding- daughter cell is smaller than mother

Question 3

molds

Answer 3

• grow as filaments-hyphae
• form a mat-mycelium
• may form transverse walls (septate hyphae) and appear to be a long chain of cells or lack walls (aseptate hyphae) and appear to be one long multinuclear cell
• growth occurs only at the tip of filaments, two daughter cells are of equal size

Question 4

fungal mitosis

Answer 4

• open- nuclear membrane disappears, like humans

- closed-buds first and nuclear membrane remains in tact whole time

Question 5

molds continued

Answer 5

• some molds reproduce sexually-zygospores, ascospores (sac), basidiospores (pedestal)
• fungi imperfecti reproduce asexually-spores vegetate into new clonal copies of parent
• distinct appearance of spores are useful for microscopic diagnosis

Question 6

five types of asexual spores

Answer 6

1. arthrospores
2. chlamydospores
3. blastospores
4. condidospores
5. sporangiospores

Question 7

arhrospores

Answer 7

form from fragmentation ends of hyphae

Question 8

chlyamidospores

Answer 8

rounded, thick walled, resistant

Question 9

blastospores

Answer 9

formed by budding

Question 10

condidospores

Answer 10

chains of spores formed at the ends of hyphae

Question 11

sporangiospores

Answer 11

formed within a sac

Question 12

thermal dimorphism

Answer 12

-some pathogenic fungi grow as molds in the environment and as yeasts in the human body

Question 13

pathogenesis-granuloma

Answer 13

• seen in the major systemic fungal diseases
• coccidio, histo, blasto
• involves CMI-macrophage and helper T

Question 14

pathogenesis-suppuration

Answer 14

• acute suppuration with neutrophils in exudate (pyogenic response)
• aspergillosis
• sporotrichosis

Question 15

pathogenesis

Answer 15

• no endotoxin
• intact skin and normal flora limit fungal growth on the body
• most of the important pathogens are transmitted by inhalation of the spores from the soil/environment
• defenses are mucous, alveolar macrophages, CMI
• PPD type skin tests for delayed hypersensitivity with fungal antigens can be used to determine exposure to environmental fungi (not normal flora)

Question 16

fungal toxins

Answer 16

• toxigenic disease is mycotoxicosis
• not infectious, caused by eating toxins
• amanita mushrooms produce amanitin and phalloidin- hepatotoxins
• ergotism caused by eating grain contaminated with claviceps purpura, which produces ergotamine and LSD
• aspergillis-aflatoxins-cancer-grains and peanuts, metabolized by liver to epoxide (carginogen), mutates p53

Question 17

fungal allergies

Answer 17

• immediate hypersensitivity response to inhaled fungal spores (aspergillus)
• asthmatic reaction-rapid bronchoconstriction mediated by IgE
• eosinophilia
• wheal and flare test reaction-type 1 hypersensitivity response
• IgE sensitized to allergen- next time causes release of histamines and cytokines

Question 18

direct microscopic examination

Answer 18

• KOH mount
• clinical specimens-sputum, lung biopsy material, skin scrapings
• tissue can be broken down with 10% KOH, which leaves fungi in tact, and stained with fungal stains-calcofluor white, methenamine silver
• characteristic asexual spores, hyphae, or yeasts may be present

Question 19

fungal culture in vitro

Answer 19

• sabouraud’s agar inhibits bacteria with low pH and antibiotics
• appearance of mycelium and asexual spores often diagnostic

Question 20

other lab tests

Answer 20

• DNA probe tests identify cultured colonies at an earlier stage than microscopy
• serologic tests-test for antifungal antibodies or spinal fluid
• useful for systemic mycoses

Question 21

amphotericin B

Answer 21

• systemic-added to IV
• originally extracted from strep nodosus
• most lifesaving antifungal drug-polyene
• effective against many systemic mycoses
• ok for pregnant
• may also be added to tissue culture to prevent fungal contamination
• broad spectrum
• binds ergosterol
• forms a transmembrane channel through which monovalent ions leak
• appears to have a less clear second mech-sequestration
• can cause toxicity in liver, blood, heart, dangerous damage to kidneys
• from spillover binding to membrane sterols
• also common for patient to have immunogenic reaction 1-3 hours after admin-fever, chills, hypotension, vomiting, headache
• only for life threatening infections

Question 22

liposomal prep

Answer 22

• less toxic

- releases drug more specifically to fungal cell wall

Question 23

nystatin and natamycin

Answer 23

• also polyenes, same mech

- too toxic for systemic but good topical

Question 24

azoles

Answer 24

-inhibit fungal cytochrome p450 and 14 alpha-demethylase required for ergosterol synthesis
-low toxicity for systemic use:
fluconazole-diflucan-candida and cryptococcal
itraconazole-histo and blasto
posaconazol-oropharyngeal candida, prophylactic for immunosuppressed
ketoconazol, clotrimazole, miconazole for topical use
-terbinafine and tolnaftate also have similar mech-topical

Question 25

echinocandins

Answer 25

• mycafungin, caspofungin, anidulafungin, more coming
• lipopolypeptides
• inhibit synthesis of beta glucan
• low toxicity-systemic
• potentially teratrogenic-class C
• effective against candida and aspergillus, not cryptococcus or mucor

Question 26

flucytosine

Answer 26

-systemic-capsules or injectable
-intrafungally converted into at least two active forms:
one inhibits fungal DNA synthesis
other inhibits certain crucial protein synthesis
-lower efficacy and faster development of resistance than ampB or azoles-combo
-can cause dangerous bone marrow toxicity, also toxic to GI, liver, kidneys, DNA, category C for pregnancy

Question 27

griseofulvin

Answer 27

• oral
• used for fungal infections of hair or nails
• enters keratin precursor cells and binds keratin
• when keratin-griseofulvin complex reaches infection, fungi bring it in by energy dependent transport
• once in fungal cell, becomes active
• inhibits mitosis by binding tubulin, interferes with MT function
• can cause liver toxicity (systemic)
• pregnancy class C