Fungal Disease Flashcards
Describe the characteristics of fungi with respect to morphology, cell composition, and biochemical functioning. Be able to explain why fungi differ from bacteria, plants, and animals
Fungi are eukaryotic, aerobic, unicellular or filamentous, heterotrophic organisms, encase in a rigid chitin cell wall, that can reproduce both sexually and asexually. Distinguishing Characteristics of Fungi: Membrane bound organelles Lack chorophyll and are not photosynthetic, they obtain organic substrates from their surroundings Rigid cell wall (chitin + cellulose) Cell membrane within cell wall containing ergosterol Most are not motile Differ from bacteria b/c eukaryotic, chitin cw Differ from plants/animals b/c ergosterol, cw
Describe three means (one Linnean, two functional) for categorizing fungi. Understand that the functional categorization schema are used cheifly to discriminate between: a) superficial and deep/systemic mycoses, or b) superficial fungi acquired from soil, animals or other humans
Linean Taxonomic Classification - based on method of sexual reproduction Clinical Classification - based on implicating human disease in regards to area of the body they infect and the depth of the tissue they infect Morphological Features
Explain the differences between yeast and hyphal forms of fungi (molds), and understand that some organisms may be dimorphic
Yeast: Unicellular growth form Reproduce via budding or fission Colonies are moist and mucoid in appearance ex: Cryptococcus neoformans, Candida albicans Hyphal (mold): Filamentous growth form (hyphae) Reproduce via spores or conidia ex: Aspergillosis Some fungi are dimorphic, meaning they may exist in a yeast or hyphal form. They typically grow in one form depending on environmental change in atmosphere, temperature or food supply.
Understand that fungi may reproduce sexually or asexually, and be able to recognize the morphology of the basic forms of asexual spores.
Asexual spores: Conidia (macro-, micro-), Sporangia, Chlamydospores, Arthrospores, Spherules, Blastoconidia, Sclerotic Bodies
Describe four means to diagnose fungal infections (empirical, direct examination, culture, tissue) and have a general understanding that other advanced techiques (serological or PCR) may be used for certain infections or in specific circumstances.
Clinical suspicion/Empiral: based on patient history and prevalence of fungal disease in a population. Also, significant cost required for further testing.
Direct Microscopic Examination: take a scraping of epithelia from skin/mucosa. Add drop of KOH or surfactant DMSO to denature human material and leave the chitinous fungal cell wall more visible, allowing for direct morphological observation. India ink illuminates mucoid capsule; Chlorazol E Black Stain, stains cell wall grey-green color.
Culture of Tissue/Material: clinical material is cultured for growth of fungal organisms. Allows for direct speciation, is cheap and does not require much professional time to collect a sample, however results are often delayed (2-4 weeks) and it is less sensitive than KOH. Lactophenol cotton blue stain used.
Histological Examination (biopsy): rapid diagnosis (2-3 days) and high sensitiviy, however higher cost and more invasive procedure (procurement of representative sample is essential). Periodic Acid Schiff with Diastase (PAS/D) highlights cell wall in purple color. Gomori methenamine silver (GMS) stains cell wall jet black. Mucicarmine stains mucopolysaccharide capsule red. Flourescent antibodies.
Serology/PCR/Other advanced techniques: blood tests for antibodies, PCR is good for speciation but not widely used, skin testing (similar principle to TB tests)
Understand the mechanism of action and selective inhibition associated with polyenes. Give an example of a drug.
Polyenes are circular (pore-like) amphoteric molecules that bind ergosterol and create a pore in the fungal membrane causing ions and other molecules to leak out of the cell.
Fungicidal
ex:
Amphotericin B - common medication for life-threatening fungal infections, but has many terrible side effects: fever, seizures and kidney damage
Nystatin: topically used for Candida infx, not absorbed when given by mouth, and too toxic to give intravenously.
Understand the mechanism of action and selective inhibition associated with azoles/triazoles. Give an example of a drug.
They inhibit the enzyme 14a - demethylase which converts lanosterol to ergosterol (required in fungal membrane synthesis). Also block steroid synthesis in humans, but to a lesser extent.
Fungistatic
Oral azoles/triazoles interfere with cytochroe P450 enzymes in the liver leading to potentially fatal drug interactions, topical drugs do not get absorbed systemically so do not have this issue.
Topical Imidzaoles: Clotrimazole, Miconazole, Econazole, Sertaconazole
Oral Imidzaoles: Ketoconazole
Oral Triazoles: Itraconazole, Fluconazole, Voriconazole, Posaconazole
Understand the mechanism of action and selective inhibition associated with allylamines/ benzylamines. Give an example of a drug.
Inhibit the enzyme squalene epoxidase, required for ergosterol synthesis. Inhibition of this enzyme leads to accumulation of squalene within the fungal cell, which is toxic and kills the cell.
Fungicidal
Ex: Terbinafine (topical and oral), adverse effects: oral may unmask Lupus like conditions
Understand the mechanism of action and selective inhibition associated with antimetabolites/ antimitotics. Give an example of a drug.
Griseofulvin inhibits fungal cell mitosis by disrupting mitotic spindle formation. Well tolerated, used in children with tinea capitis. Fungistatic
Flucytosine is transported in to fungal cells by cytosine permease and is then converted in the cytoplasm to 5-fluorouracil which is a pyrimidine anti-metabolite that interrupts DNA synthesis, inhibiting growth. Fungistatic
Understand the mechanism of action and selective inhibition associated with unique antifungals. Give an example of a drug.
Ciclopirox olamine chelates polyvalent metal cations leading to the inhibition of many fungal enzymes. Fungastatic but fungicidal in vitro against broad spectrum fungal organisms.
Echinocandins inhibit the synthesis of glucan in the fungal cell walls via inhibition of the enzyme, 1,3 beta-glucan synthase
Conidia (macro-, micro-)
Sporangia
similar to macroconidia, except that the asexual spores (endospores) are enclosed in a membranous sac that breaks and the entire structure is borne by a sporangiphore.
Chlamydospore
thick-walled, round spores that are highly resistant to adverse environmental conditions. Classified based on where they form along the hyphae
Arthrospores
Like chlamydospores, arthrospores develop along the hyphae, but in general they are more numerous and elongated, often with a shape likened to a “barrel” (Coccidioides immitis)
Spherules
large, asexual spores that develop during the yeast phase of some organisms growth. Spherules in tissue are filled with endospores.
Blastoconidia
yeasts that bud asymmetrically are said to for blastoconidia
Sclerotic Bodies (Medlar bodies)
thick-walled, environmentally protective forms of yeast that are produced by some medically-relevant fungi that reproduce by fission (split down the middle - equal cell division)
