Fungus 1 Flashcards
defining properties of fungi
- 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
yeasts
single cells
-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 the tip of filaments, two daughter cells are of equal size
fungal mitosis
- open- nuclear membrane disappears, like humans
- closed-buds first and nuclear membrane remains in tact whole time
molds continued
- 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
five types of asexual spores
- arthrospores
- chlamydospores
- blastospores
- condidospores
- sporangiospores
arhrospores
form from fragmentation ends of hyphae
chlyamidospores
rounded, thick walled, resistant
blastospores
formed by budding
condidospores
chains of spores formed at the ends of hyphae
sporangiospores
formed within a sac
thermal dimorphism
-some pathogenic fungi grow as molds in the environment and as yeasts in the human body
pathogenesis-granuloma
- seen in the major systemic fungal diseases
- coccidio, histo, blasto
- involves CMI-macrophage and helper T
pathogenesis-suppuration
- acute suppuration with neutrophils in exudate (pyogenic response)
- aspergillosis
- sporotrichosis
pathogenesis
- 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)
fungal toxins
- 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
fungal allergies
- 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
direct microscopic examination
- 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
fungal culture in vitro
- sabouraud’s agar inhibits bacteria with low pH and antibiotics
- appearance of mycelium and asexual spores often diagnostic
other lab tests
- 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
amphotericin B
- 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
liposomal prep
- less toxic
- releases drug more specifically to fungal cell wall
nystatin and natamycin
- also polyenes, same mech
- too toxic for systemic but good topical
azoles
-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
echinocandins
- 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
flucytosine
-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
griseofulvin
- 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
