2-31 Fungi I Flashcards Preview

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Flashcards in 2-31 Fungi I Deck (13):
1

What are the defining properties of fungi?

  • Eukaryotic
  • 80S ribosomes
  • Cell wall of chitin and beta-glucan (no vulnerability to anti-peptidoglycan antibiotics or enzymes)
  • Cell membrane contains ergosterol instead of cholesterol (vulnerable to amphotericin B and azole drugs)
  • Some obligate aerobes; no obligate anaerobes
  • Require preformed organic carbon nutrient source
  • Most are environmental; C. albicans is normal flora
  • Can grow in drier, more acidic, and higher-osmotic-pressure environments than bacteria

2

What are the 2 major types of fungi?

  1. Yeasts: single cells that reproduce by budding (daughter cell is smaller than mother)
  2. Molds: 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 tip of filament;  two daughter cells are of equal size

3

How does fungal mitosis differ from animal mitosis?

4

Do fungi reproduce sexually?

Yes.

1. Zygospores form single large sexual spores with thick walls 2. Ascospores form sexual spores in a sac (ascus)
3. Basidiospores form sexual spores on the tip of a pedestal

(basidium)

5

Do fungi reproduce asexually?

Fungi imperfecti reproduce w/o sexual spores (includes most pathogens); Asexual spores are conidia:

  • Arthrospores: form from fragmentation of ends of hyphae
  • Chlamydospores: rounded, thick-walled, resistant
  • Blastospores: formed by budding
  • Condidospores: chains of spores formed at the ends of hyphae
  • Sporangiospores: formed within a sac

6

What is thermal dimorphism?

some pathogenic fungi grow as molds in the environment and as yeasts in the human body (depends on the temperature to which they are exposed).

Thermal dimorph life cycle:

  • Mold form grows in moist environment
  • Environment dries → conidia form
  • Conidia are inhaled by passing animals
  • In the proper host animal, conidia will germinate in lungs and convert to
  • yeast form
  • Yeast form enters bloodstream and travels to GI, is excreted in feces
  • Yeast form converts back to mold form in this new nutrient-rich, moist environment

7

What are some recurring patterns in fungal pathogenesis?

Granuloma formation seen in the major systemic fungal diseases (coccidiodomycosis, histoplasmosis, blastomycosis); involves CMI: macrophage and helper T

Acute suppuration w/ neutrophils in exudate: pyogenic response (aspergillosis, sporotrichosis)

Fungi lack 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 soil/environment; defenses are mucus, alveolar macrophages, and CMI

PPD-type skin tests for delayed hypersensitivity with fungal antigens can be

used to determine exposure

8

Fungal toxins and allergies

9

How can lab techniques diagnose fungal infection?

Direct microscopic examination: tissue can be broken down w/ 10% KOH (leaves fungi intact), orstained w/ fungal stains (calcofluor white, methenamine silver). Called a KOH mount.

Characteristic asexual spores, hyphae, or yeasts may be present

Spherules of Coc. immitis in sputum if coccidioidomycosis

Wide capsule of Cryptococcus neoformans in CSF if cryptococcal

meningitis

Culture of fungus

Sabouraud’s agar inhibits bacteria w/ low pH and antibiotics

Appearance of mycelium and asexual spores often diagnostic

DNA probe tests identify cultured colonies at an earlier stage than microscopy

Serologic tests

Test for antifungal antibodies in serum or spinal fluid

Useful for systemic mycoses

10

What are the general characteristics of antifungal agents?

Fungi do not have:

Peptidoglycan cell walls

70S ribosomes

... and so are not vulnerable to antibiotics that target them

Most antifungals target ergosterol

11

What is amphotericin B?

(Fungizone) (systemic)

Binds ergosterol

Disrupts membranes

Can cause renal toxicity; liposomal prep is less toxic

Most important antifungal drug; a polyene effective against many

systemic mycoses

The drug of choice for systemic mycosis in pregnancy: all the

others are potential teratogens

Nystatin is also a polyene, same mech, too toxic for systemic use

•Broad spectrum
•Binds ergosterol
•Forms a transmembrane channel through which monovalent  ions leak (K+, Na+, H+, Cl-)
•Appears to also have a less-clear second mechanism
•Can cause toxicity in liver, blood, heart, dangerous damage to kidneys. 
•Toxicity is from spillover binding to human membrane sterols
•Also common for patient to have an immunogenic reaction 1-3hrs after admin: high fever, shaking chills, hypotension, vomiting, headache
•Used only for life-threatening infections

but good for topical

12

What are azoles?

 Azoles inhibit fungal cytochrome   P450 and 14alpha-demethylase,   required for ergosterol synthesis

Low toxicity azoles for systemic use:

1.Fluconazole (Diflucan) for candida and cryptococcal infections

2.Itraconazole (Sporanox) for histoplasmosis and blastomycosis

3.Posaconazole (Noxafil) for oropharyngeal candidiasis, prophylactic for immunosuppressed

13

What are echinocandins?

•Lipopolypeptides

•Inhibit synthesis of beta-glucan

•Low toxicity: Systemic

•Potentially teratogenic (Class C)

•Effective against Candida and Aspergillus, not Cryptococcus or Mucor