Fungi Structure and Function and Antifungals Flashcards
Defining Properties of Fungi
- eukaryotic- a lot of some of the same things we have (80S ribsomes)
- cell wall of chitin and beta glucan- need to use anti-beta-glucan drugs instead of anti-peptidoglycan
- cell membrane has ergosterol instead of cholesterol- amphoteric B and azole drugs
- some are obligate aerobes, not are obligate anaerobes
- require preformed organic carbon nutrient source (heterotrophs)
- most are environmental, C albicans is normal flora
Transmission of fungi
- very little person to person
- good news: little selective pressure for drug resistance
- bad news: no eradication
- can grow in colder, drier, more acidic, and higher osmotic pressure environments than bacteria- more superficial cutaneous infections
Yeasts
- one of the major types of fungi
- single cells
- reproduce by budding: daughter cell is smaller than mother
Molds
- one of the major types of fungi
- 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
Open vs closed mitosis
- fungal mitosis is similar but no identical to animal mitosis
- primary difference: many fungi have closed mitosis (nuclear envelope does not disperse)
Mold sexual reproduction
- some molds reproduce sexually
- zygospores form single large sexual spores with thick walls
- ascospores form sexual spores in a sac (ascus)
- basidiospores form sexual spores on the tip of a pedestal) basidium
Fungi imperfecti
- reproduce asexually: spores vegetate into new clonal copies of parent. The distinct appearances of the different spores are useful for microscopic diagnosis
- five types of asexual spres (conidia)
1) arthrospores: form from fragmentation of ends of hyphae
2) chlamydospores: rounded, thick-walled, resistant
3) blastospores: formed by budding
4) Condidospores: chains of spores formed at the end of hyphae
5) Sporangiospores: formed within a sac (may be a separate grouping
Reproduction in environment and body
- in the environment, most molds have both sexual and asexual phases, can get very complex
- in the body, fungal reproduction is usually asexual cell division, often yeastlike because of thermal dimorphism
Thermal dimorphism
-some pathogenic fungi grow as molds in the environment and as yeasts in the human body
Fungal Granuloma formation
- seen in the major systemic fungal diseases: Coccidiodomycosis, histoplasmosis, blastomycosis
- involves CMI: macrophage and helper T
Pathogenesis of fungal infections
- granuloma formation
- acute suppuration with neutrophils in exude (pyogenic response)- aspergillosos, sporotrichosis
- no endotoxin
- intact skin and normal flora limit fungal growth on 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 to environmental fungi (not normal flora)
Fungal toxins
- toxigenic disease is mycotoxicosis
- not infectious, caused by eating toxins
- example: amanita mushrooms produce amanitin and phalloidin, potent hepatotoxins
- example: ergotism caused by eating grain contaminated with Claviceps purpura which produces ergotamine and LSD
- example: aspergillus flavus produces aflatoxins, believed to be linked to hepatic carcinoma in humans- ingested with spoiled grains and peanuts, metabolized by liver to epoxide (carcinogen), mutates p53 tumor suppressor gene
Fungal allergies
- immediate hypersensitivity response to inhaled fungal spores (usually aspergillus)
- asthmatic reaction: rapid bronchoconstriction mediated by IgE
- eosinophilia
- wheal and flare test reaction: type 1 hypersensitivity response (same as to a mosquito bite)
Direct microscopic examination of fungi
-KOH mount
-clinical specimens: sputum, lung biopsy material, skin scrapings
-tissue can be broken down with 10% KOH, which leaves fungi intact, and stained with fungus stains (calcofluor white, methanamine silver) KOH mount
-characterisitc asexual spores, hyphae, or yeasts may be present
-example: spherules of Coc. immitis
Wide capsule of Cytococcus neoformans
Culture of fungus
- Sabouraud’s agar inhibits bacteria w/ low pH and antibiotics
- appearance of mycelium and asexual spores often diagnostic