What are the defining properties of fungi?
- 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
What are the 2 major types of fungi?
Yeasts: single cells that reproduce by budding (daughter cell is smaller than mother)
- 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
How does fungal mitosis differ from animal mitosis?
Do fungi reproduce sexually?
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
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
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
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
Fungal toxins and allergies
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
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
Test for antifungal antibodies in serum or spinal fluid
Useful for systemic mycoses
What are the general characteristics of antifungal agents?
Fungi do not have:
Peptidoglycan cell walls
... and so are not vulnerable to antibiotics that target them
Most antifungals target ergosterol
What is amphotericin B?
Can cause renal toxicity; liposomal prep is less toxic
Most important antifungal drug; a polyene effective against many
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
but good for topical
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
What are echinocandins?
•Inhibit synthesis of beta-glucan
•Low toxicity: Systemic
•Potentially teratogenic (Class C)
•Effective against Candida and Aspergillus, not Cryptococcus or Mucor