Fungi Structure and Function and Antifungals Flashcards Preview

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Flashcards in Fungi Structure and Function and Antifungals Deck (22)
1

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

2

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

3

Yeasts

-one of the major types of fungi
-single cells
-reproduce by budding: daughter cell is smaller than mother

4

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

5

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)

6

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

7

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

8

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

9

Thermal dimorphism

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

10

Fungal Granuloma formation

-seen in the major systemic fungal diseases: Coccidiodomycosis, histoplasmosis, blastomycosis
-involves CMI: macrophage and helper T

11

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)

12

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

13

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)

14

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

15

Culture of fungus

-Sabouraud's agar inhibits bacteria w/ low pH and antibiotics
-appearance of mycelium and asexual spores often diagnostic

16

Lab Diagnosis of fungal infections

-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

Antifungal agents

Fungi do not have:
-peptidoglycan cell walls
-70S ribosomes
-and so are not vulnerable to antibiotics that target them
-most antifungals target ergosterol

18

Amphotericin B (Fungizone

-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

Azoles

-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

Echinocandins

-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

Flucytosine

-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

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