Fungi Structure and Function and Antifungals Flashcards

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1
Q

Defining Properties of Fungi

A
  • 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
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2
Q

Transmission of fungi

A
  • 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
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3
Q

Yeasts

A
  • one of the major types of fungi
  • single cells
  • reproduce by budding: daughter cell is smaller than mother
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4
Q

Molds

A
  • 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
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5
Q

Open vs closed mitosis

A
  • fungal mitosis is similar but no identical to animal mitosis
  • primary difference: many fungi have closed mitosis (nuclear envelope does not disperse)
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6
Q

Mold sexual reproduction

A
  • 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
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7
Q

Fungi imperfecti

A
  • 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
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8
Q

Reproduction in environment and body

A
  • 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
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9
Q

Thermal dimorphism

A

-some pathogenic fungi grow as molds in the environment and as yeasts in the human body

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10
Q

Fungal Granuloma formation

A
  • seen in the major systemic fungal diseases: Coccidiodomycosis, histoplasmosis, blastomycosis
  • involves CMI: macrophage and helper T
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11
Q

Pathogenesis of fungal infections

A
  • 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)
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12
Q

Fungal toxins

A
  • 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
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13
Q

Fungal allergies

A
  • 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)
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14
Q

Direct microscopic examination of fungi

A

-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

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15
Q

Culture of fungus

A
  • Sabouraud’s agar inhibits bacteria w/ low pH and antibiotics
  • appearance of mycelium and asexual spores often diagnostic
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16
Q

Lab Diagnosis of fungal infections

A
  • direct microscopy
  • culture
  • 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
17
Q

Antifungal agents

A

Fungi do not have:

  • peptidoglycan cell walls
  • 70S ribosomes
  • and so are not vulnerable to antibiotics that target them
  • most antifungals target ergosterol
18
Q

Amphotericin B (Fungizone

A
  • 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 pregnany
  • may be added to tissue culture to prevent fungal contamination
  • broad spectrum
  • forms a transmembrane channel through which monovalent ions leak
  • used only for life-threatening infections
  • Nystatin- same mech, use for topical
19
Q

Azoles

A
  • inhibit ergosterol synthesis- the fungal cytochrome P450 and 14 alpha demethylase
  • low toxicity azoles:
  • fluconazole- candida and cryptococcal infections
  • itraconazole- for histoplasmosis and blastomycosis
  • posaconazole for oropharyngeal candidiasis, prophylatic for immunosuppressed
  • ketoconazole, clotrimazole, miconazole for topical use
  • Terbinafine and Tolnaftate for topical use
20
Q

Echinocandins

A
  • mycafungin, caspofungin, anidulafungin, more coming
  • lipopolypeptides
  • inhibit synthesis of beta-glucan
  • low toxicity: systemic
  • potentially tetrogenic (class C)
  • effective against Candida and Aspergillus not Crytococus or Mucor
21
Q

Flucytosine

A
  • systemic: capsule or injectable
  • infrafungally converted into at least two active forms- one inhibits fungal DNA synthesis, other inhibits certain crucial protein synthesis
  • inhibits candida and cryptococcus
  • lower efficacy and faster development of resistance than Amphotericin B or azoles
  • can cause dangerous bone marrow toxicity, also toxic to GI, liver, kidneys, CNS, category C for pregnancy
22
Q

Griseofulvin

A
  • 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 microtubule function
  • can cause liver toxicity (systemic)
  • pregnancy class C